TOOL© TO IMPROVE HYPERPHOSPHATEMIA IN PATIENTS WITH CHRONIC … · 2013-10-25 · ii Intensive Dietary Education Using the Phosphorus Point System Tool© to Improve Hyperphosphatemia

INTENSIVE DIETARY EDUCATION USING THE PHOSPHORUS POINT SYSTEM

TOOL© TO IMPROVE HYPERPHOSPHATEMIA IN

PATIENTS WITH CHRONIC KIDNEY DISEASE

by

Amanda Jane Degen

A thesis submitted in conformity with the requirements

for the degree of Master of Science

Graduate Department of Nutritional Sciences

University of Toronto

© Copyright by Amanda Jane Degen (2009)

ii

Intensive Dietary Education Using the Phosphorus Point System Tool©

to Improve Hyperphosphatemia in Patients with Chronic Kidney Disease

Master of Science, 2009

Amanda Jane Degen

Graduate Department of Nutritional Sciences

University of Toronto

Abstract

Background: High serum phosphorus (hPhos) is common in chronic kidney disease

(CKD) and increases the risk of metastatic calcification. Guidelines advise patients with hPhos

to restrict dietary phoshorus intake to 800-1000mg/day, and compliance with this diet can be

challenging. Innovative education may improve compliance. Hypothesis: Intensive dietary

education using the Phosphorus Point System Tool© (PPS) will result in lower serum

phosphorus levels compared to standard education (SE). Methods: This study compared the

effectiveness of the PPS to SE on 1) serum phosphorus, 2) dietary phosphate intake, knowledge

and satisfaction in pre-dialysis CKD. Results: The PPS reduced 12 week serum phosphorus by

0.16 mmol/L (95% CI 0.37 to -0.05, p=0.130) when controlling for baseline. Dietary

phosphorus and protein intake decreased significantly at week 6 on PPS compared to SE (p=

0.026, p=0.050; respectively). Summary: Although there was a trend indicating the tool may

reduce serum phosphorus levels, further research is needed.

iii

Acknowledgements

I would like to firstly acknowledge the support I have received throughout the duration

of my Masters degree from Dr. Pauline Darling. I greatly appreciate the guidance she provided

me and the invested commitment she made to the project. Pauline devoted generous amounts of

time to ensure my Masters thesis experience was positive. I would also like to thank Carol

Huang RD, for her assistance in setting up the study, connecting us with the Progressive Renal

Disease Clinic (PRDC) team, and devoting her time to the project; as well as her involvement in

participant recruitment. Dr. Sandra Donnelly was invaluable in providing insight into our study

design, and was a valuable collaborator on which we could rely for insightful feedback and

support throughout the entire study duration. I am indebted to Ada Kazman, who provided me

with insight to understand the PRDC participants’ backgrounds, and who helped me to obtain

the required bloodwork for many of the participants. I would also like to thank the remaining

St. Michael’s Hospital (SMH) nephrologists who were more than willing to facilitate

recruitment in all the pre-dialysis clinics at SMH; thank you to Dr. M. Goldstein, Dr. S. Nessim,

Dr. R. Prasad, Dr. M. Schreiber, Dr. R. Wald.

I would like to thank Kevin Thorpe, Biostatistician with the SMH Li Ka Shing

Knowledge Institute for his guidance on our statistical analyses. Thank you to my advisory

committee from the University of Toronto, Dr. V. Tarasuk and Dr. T. Wolever, for their

guidance throughout the duration of the project. Thank you to the Department of Nutritional

Sciences at the University of Toronto for an excellent graduate experience. Lastly, I would like

to thank my family and loved ones for their continued support throughout this experience. I am

eager to use the skills and experiences gained from this project in the next stages of my career

and am looking forward to the next chapter. Thank you sincerely.

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Table of Contents

List of Tables vi List of Figures vii List of Common Abbreviations viii 1.0 Introduction 1 2.0 Literature review 3

2.1 Chronic kidney disease 3 2.2 Phosphorus metabolism in healthy individuals 5

2.2.1 Phosphorus metabolism and body content of phosphorus 5 2.2.2 Renal phosphorus handling 7

2.3 Chronic kidney disease and hyperphosphatemia 7 2.3.1 Altered phosphorus metabolism in chronic kidney disease 7 2.3.2 Hyperphosphatemia and its association with increased mortality 9

and morbidity 2.3.2.1 Secondary hyperparathyroidism 11 2.3.2.2 Renal osteodystrophy 11 2.3.2.3 Soft tissue and vascular calcification 12 2.3.2.4 Cardiovascular complications 12 2.3.2.5 Atherosclerosis and dyslipidemia 15 2.3.2.6 Summary 15

2.4 Hyperphosphatemia management 16 2.4.1 Phosphate binders 16 2.4.2 Dialysis 18 2.4.3 Dietary phosphate restriction 18

2.4.3.1 Phosphorus food sources 19 2.4.3.2 Phosphorus additives 19

2.4.4 Evidence supporting dietary phosphate restriction 21 2.4.5 Protein restriction to delay the progression of CKD 23

2.5 Effectiveness of Educational Interventions in CKD 24 2.5.1 Evaluating effectiveness of education 24 2.5.2 Phosphatemia reduction with intensive dietary education in 25

hemodialysis 2.5.3 Phosphatemia reduction with intensive dietary education in 29

peritoneal dialysis 2.5.4 Impact of patients’ knowledge level on outcomes 31 2.5.5 Dietary adherence and satisfaction with phosphate restriction 33 2.5.6 Innovations in the area of phosphorus control 35

3.0 Rationale, Hypothesis and Objectives 36 4.0 Methods 40

4.1 Study design 40 4.2 Eligibility and recruitment 40

4.2.1 Eligibility 40 4.2.2 Recruitment method 41

4.3 Study procedures 41 4.3.1 Standard Education 42 4.3.2 Intervention PPS Education 45 4.3.3 Data Collection 46

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4.4 Serum measures 46 4.5 Estimated dietary intake 48 4.6 Dietary satisfaction measurement 50 4.7 Renal disease concept comprehension measurement 51 4.8 Statistical analyses and sample size estimation 51

5.0 Results 54 5.1 Participant recruitment 54 5.2 Characteristics of participants 56 5.3 Serum phosphorus and other biochemical measures 56 5.4 Dietary outcomes 60

5.4.1 Dietary and phosphate binder intake 60 5.4.2 Phosphorus knowledge scores 65 5.4.3 Dietary satisfaction scores 65 5.4.4 Qualitative satisfaction data 65 5.4.5 Processed food intake 70

6.0 Discussion 71 6.1 Serum phosphorus levels 71 6.2 Renal function 73 6.3 Phosphate binders 73 6.4 Dietary intake 73 6.5 Phosphorus knowledge 76 6.6 Dietary satisfaction 76 6.7 Qualitative satisfaction 77 6.8 Processed foods 78 6.9 Limitations 80 6.10 Future Directions 81

7.0 Conclusions 84 8.0 References 86 9.0 Appendices 92

Form 1 – St. Michael’s Hospital Consent Form 92 Form 2 – Sunnybrook Hospital Consent Form 96 Form 3 – Chart Data Collection Form 103 Form 4 – Inclusion/Exclusion Form 105 Form 5 – 24-Hour Dietary Recall 106 Form 6 – Processed Food Intake 109 Form 7 – Dietary Satisfaction Questionnaire 110 Form 8 – Phosphorus Knowledge Test 115 Form 9 – Choose/Avoid Handout 118 Form 10 – The Phosphorus Point System© Tool 120 Form 11 –Phosphorus Point Food Tracker 129 Form 12 – Qualitative Data Form 130 Form 13 – Phosphorus Additives Handout 131

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List of Tables

Table 2.0 Summary of Studies Examining Serum Phosphorus in Response to Dietary 30 Intervention in Hemodialysis Patients Table 4.0 Schedule of Key Study Measurements 44

Table 5.0 Clinical and Demographic Characteristics of Participants 57

Table 5.1 Effect of Standard Education (SE) and Phosphorus Point System Tool (PPS) on 58 Biochemical Variables in Participants at Week 6 Table 5.2 Effect of Standard Education (SE) and Phosphorus Point System Tool (PPS) on 59 Biochemical Variables in Participants at Week 12 Table 5.3 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 62 on Estimated Mean 2-Day Dietary Intake of Phosphorus, and Selected Nutrients and Phosphate Binders in Participants at Week 6 Table 5.4 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 63 on Estimated Mean 2-Day Dietary Intake of Phosphorus, and Selected Nutrients and Phosphate Binders in Participants at Week 12 Table 5.5 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 66 on Knowledge Test Scores of the Participants at Week 6 Table 5.6 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 66 on Knowledge Test Scores of the Participants at Week 12 Table 5.7 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 67 on Satisfaction of the Participants at Week 6 Table 5.8 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) 67 on Satisfaction of the Participants at Week 12 Table 5.9 Summary of Qualitative Data from Dietary Satisfaction Questionnaires and 68 Follow-up Telephone calls Table 5.10 - Effect of Standard Education (SE) and the Phosphorus Point System 69 Tool (PPS) on Dietary Intake of Processed Foods Over Time (servings per week)

vii

List of Figures

Figure 2.0 - Stages of Chronic Kidney Disease 4

Figure 2.1 Phosphorus Balance in a Healthy Individual 6

Figure 4.0 Twelve Week Study Design 43

Figure 5.0 Profile of Subject Recruitment and Study Completion 55

Figure 5.1 Relationship between Serum Phosphate and Kidney Function as measured 61 by Glomerular Filtration rate (GFR, mL/min/1.73 m2) in participants with Chronic Kidney Disease at Baseline Figure 5.2 Relationship between Serum Phosphate and Kidney Function as measured by 61 Glomerular Filtration rate (GFR, mL/min/1.73 m2) in participants with Chronic Kidney Disease at Week 12

viii

List of Common Abbreviations

ALP Alkaline phosphatase C/A Choose/Avoid Tool CaxP Calcium phosphate product CAC Coronary Artery Calcification CAD Coronary Artery Disease CKD Chronic Kidney Disease EAR Estimated average intake requirement ESRD End-stage Renal Disease GFR Glomerular filtration rate HD Hemodialysis KDOQI Kidney Disease Quality Outcomes Initiative LVH Left ventricular hypertrophy MDRD Modification of Diet in Renal Disease PD Peritoneal dialysis PTH Parathyroid hormone PPS Phosphorus Point System Tool© RD Registered Dietitian RRT Renal replacement therapy SE Standard Education SD Standard Deviation SMH St. Michael’s Hospital TUL Tolerable upper intake level

1

1.0 Introduction

Patients with chronic kidney disease (CKD) have reduced kidney function, which worsens

with disease progression. As the function of the kidney declines, the ability of the kidney to

excrete phosphorus is reduced, resulting in the accumulation of phosphorus. Serum phosphorus

levels increase, and to accommodate this, patients with hyperphosphatemia must reduce their

consumption of phosphorus containing foods. Although phosphorus is an important mineral that

is required by all cells of the human body (1), there is heightened awareness that increased

serum phosphorus levels are related to an increase in morbidity and mortality in hemodialysis

patients (2,3). Hyperphosphatemia increases the risk of developing metastatic calcification,

cardiovascular disease, renal osteodystrophy and secondary hyperparathyroidism.

Dietary phosphorus restriction in hyperphosphatemic patients with CKD is indicated for the

management of hyperphosphatemia; as well as the correction or prevention of secondary

hyperparathyroidism and cardiovascular damage (4) . Patients with hyperphosphatemia require

dietary education to learn dietary phosphate management strategies. Renal diets are among the

most complex of disease-specific diets, and thus there are various strategies and theories for

improving dietary compliance with these complex diets. Numerous studies have been

completed in the hemodialysis population investigating whether more intensive or innovative

education improves serum phosphorus levels over standard education. It is unclear as to what is

the best strategy for improving serum phosphorus levels. Research of this nature has yet to be

performed in the pre-dialysis CKD population. The Phosphorus Point System Tool© was

developed at St. Michael’s Hospital with the intent to improve serum phosphorus levels through

improving dietary compliance. This tool was shown to be effective in reducing serum

phosphorus levels in peritoneal dialysis patients after one month of its use.

2

Thus the aim of the study was to determine the effectiveness of innovative, intensive

dietary phosphorus education using the Phosphorus Point System Tool© to reduce serum

phosphorus levels in patients with pre-dialysis CKD.

3

2.0 Literature review

2.1 Chronic kidney disease

Chronic kidney disease is defined as the presence of kidney damage or reduced kidney

function for at least 3 months (5). CKD has three main causes; diabetic nephropathy, renal

vascular disease, and glomerulonephritis (6). Five stages of progression exist in CKD, from its

beginning stage 1 to end-stage renal disease at stage 5 (Figure 2.0). The glomerular filtration

rate (GFR) is a measure of kidney function, and determines the stage of kidney disease. GFR is

based on the measure of serum creatinine, age, gender, and race. When patients reach GFR <30

mL/min/1.73 m2 or stage 4, they should seek consultation from a nephrologist. Stage 5 CKD is

also known as end-stage renal disease; wherein the kidneys are functioning at a GFR less than

15 mL/min/1.73 m2 and the initiation of renal replacement therapy is necessary (5).

Approximately two million Canadians either have CKD, or are at risk of developing

CKD (6). Approximately fourteen Canadians each day find out their kidneys have failed (6).

End-stage renal disease (ESRD) which requires renal replacement therapy (RRT) is on the rise

with 15.8 per 100,000 patients being treated in Canada in 2001, an increase of 18.8% in five

years (7,8). Although the present study is focused on a pre-end-stage renal disease population, it

is important to note the prevalence of the disease in its most debilitating form as chronic kidney

disease typically progresses toward ESRD. In 2004, 30,924 Canadians were on RRT; and this

number is expected to double by 2014 (6).

There are three main functions of the kidney; excretory, endocrine and metabolic (9).

The most important function of the kidney involves excretion and regulation of body fluids,

organic compounds and minerals (9). The kidney is also involved in the production of

hormones, such as renin, erythropoietin and 1,25-dihydroxychoecalciferol (9). The functions of

4

Figure 2.0 - Stages of Chronic Kidney Disease. Adapted from the National Kidney Foundation www.kidney.org

5

the kidney becomes impaired when the kidney is diseased (5). Patients with kidney disease

often require alterations in their diet as there is a decrease in the renal clearance of water,

sodium, potassium, calcium, magnesium and phosphorus (10). Accumulation of certain proteins

can occur, as well as decreased absorption of other vitamins and minerals (10).

2.2 Phosphorus Metabolism in Healthy Individuals

2.2.1 Phosphorus metabolism and body content of phosphorus

Bones contain phosphorus in the form of hydroxyapatite, plasma membranes contain

phosphorus as a part of phospholipids, the production and storage of energy requires adequate

phosphorus, phosphorus is a component of enzymes, phosphorylation is responsible for

activation of many hormones, and phosphorus is involved in acid-base regulation as a buffer at

the surface of bone (1).

A typical 70-kg man contains approximately 700g of phosphorus (1,11). Of this total

body phosphorus, about 85% is within the bone and teeth, 14% within the soft tissue and 1%

within the extracellular space. Intracellular phosphorus is typically in organic compounds, as

creatinine phosphate, adenosine monophosphate (AMP) and triphosphate (ATP). Phosphorus is

the most abundant anion within the cell (1). Figure 2.1 depicts phosphorus balance in a healthy

individual.

Phosphorus is absorbed by the small intestine via passive diffusion along an

electrochemical gradient and also active transport using the sodium phosphate co-transporter

type 2b across cells (11). Between 60-70% of the phosphorus consumed is absorbed via the

intestines (12,13). 30% of the phosphorus absorbed is excreted through the gastrointestinal tract

and 70% is excreted by the kidneys (14). The quantity of phosphorus absorbed by the intestines

is directly related to the quantity present in the diet and its bioavailability (11). The

6

Figure 2.1- Phosphorus Balance in a Healthy Individual. Adapted from Urribarri (2007)

7

maintenance of calcium homeostasis is responsible for exchanges between phosphorus in the

extracellular space and bone (15).

Dietary intake of phosphorus in healthy Canadian adults from the Canadian Community

Health Survey in 2004 indicates the mean and standard deviation (SD) intake in males age 51-70

is 1417 (22) mg and in females age 51-70 is 1161 (18) mg (16). The estimated average intake

requirement (EAR) is 580 mg/day for adults 19 years of age and older, and the tolerable upper

intake level (TUL) is 4000 mg/day (17). Dietary intake in healthy individuals is balanced with

fecal and urinary output; resulting in neutral balance of phosphate within the body (12).

2.2.2 Renal phosphorus handling

Phosphorus that is not bound to proteins is freely filtered in the glomerulus, and most

phosphorus is not bound to albumin (11,13). Phosphorus is reabsorbed along the nephron, with

about 75% of the filtered being recovered by the proximal tubule, 10% by the distal tubule and

15% excreted in the urine (15). The main phosphorus transporter of the proximal tubule is the

sodium co-transported type 2a; whose activity is decreased by parathyroid hormone and

increased by low serum phosphorus and low serum 1,25(OH)2 vitamin D (13,15). The

regulators of renal phosphate balance are glomerular filtration and PTH (1).

2.3 Chronic kidney disease and hyperphosphatemia

2.3.1 Altered Phosphorus Metabolism in Chronic Kidney Disease

Chronic kidney disease and end-stage renal disease are typically associated with

disturbances in the metabolism of calcium, phosphorus, and magnesium (18). In patients with

chronic renal disease there is a reduced renal clearance of phosphorus (10), thus resulting in

positive phosphate balance. A hormonal imbalance also occurs as a result of declining kidney

function, particularly affecting parathyroid hormone (PTH) and calcitriol (18).

8

Hyperphosphatemia occurs as a result of impaired renal phosphate excretion, where

there is a difference between the rate at which phosphate enters and is excreted by the kidneys

(12,19-22). Hyperphosphatemic patients with CKD often have to limit dietary intake of

phosphorus, as declining renal function increases serum phosphorus levels (18,23-26).

Although urinary phosphorus excretion is impaired in CKD, elevated serum phosphorus

levels are masked, and serum phosphate levels are typically maintained within normal serum

levels of 0.80-1.50 mmol/L until CKD reaches Stage 4 (GFR < 30) (12,14,27). This

compensation in serum values is facilitated by an increase in PTH secretion that reduces the

fraction of filtered phosphate proximally reabsorbed (12,14, 27). Increased PTH synthesis and

secretion, as well as the resulting parathyroid gland hyperplasia in response to elevated serum

phosphate is an agreed upon consequence of CKD; however, the mechanisms in which this

occurs are unclear (2). The hyperplasia appears to persist even when phosphorus levels are

corrected, and thus it is crucial to intervene early and control phosphorus levels to prevent or

inhibit the hyperplasia and possible progression to secondary hyperparathyroidism (2).

Nakajima et al. (2009) demonstrated when parathyroid tissue obtained from patients with

secondary hyperparathyroidism were cultured in medium containing various concentrations of

phosphorus, PTH release was stimulated in a dose-dependent manner (28). As well, higher

concentrations of phosphorus stimulated parathyroid cell proliferation within an organ culture

system, however the mechanism through which this occurs still remains to be determined (28).

The enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, which produces renal vitamin

D, is inhibited by high phosphate levels and thus the absorption of calcium from the intestine is

reduced with hyperphosphatemia (12,22). Hyperphosphatemia also results in hypocalcemia due

to the formation of a calcium-phosphate product (CaxP) that is deposited into bone or other

tissues (13).

9

The resultant effects of the decline in kidney function on PTH, calcitriol and mineral

status have various short and long-term effects that can be diminished by improved phosphorus

control.

2.3.2 Hyperphosphatemia and its association with increased mortality and morbidity

Block et al. (1998) were able to demonstrate that elevated serum phosphorus was

associated with an increased risk of mortality and morbidity in hemodialysis patients. The

relative mortality risk was 1.06 per 0.32 mmol/L higher serum phosphorus; which suggests a 6%

higher mortality risk for each 0.32 mmol/L higher serum phosphorus (29). As well, patients

with serum phosphorus between 2.13 to 2.52 mmol/L exhibited a 13% higher risk of mortality

than patients in the hemodialysis reference range for phosphorus of 1.49 to 1.78 mmol/L (29).

Patients within the highest serum phosphorus quintile (2.55 to 5.46 mmol/L) had a 34% higher

relative mortality risk than those patients within the reference range (29). Additionally, the

calcium-phosphorus product was found to be associated with an increase in mortality, as

patients with a CaxP greater than 5.81 mmol/L had a 34% (1.34) greater risk of death compared

with those with a CaxP in the reference range between 3.39 and 4.20 mmol/L (29). The

researchers were not clear on the exact mechanism through which hyperphosphatemia

contributes to the elevated risk of mortality (29). Ganesh et al (2001) hypothesized that the

increased risk of mortality was related to hyperphosphatemia, elevated CaxP and PTH

increasing the risk of cardiac death versus other causes of mortality. Their research found that a

0.232 mmol/L increase in serum phosphorus levels in prevalent hemodialysis patients resulted in

a 9% higher relative risk of death related to CAD (p<0.0005) and a 6% increased risk of sudden

death (p<0.001) (30). It was also shown that this increased risk of death attributed to CAD

could not be explained by factors thought to be contributing to death, such as missed dialysis

sessions, inadequate dialysis, anemia, nutrition deficiencies, or pre-existing vasculopathy (30).

10

Strong relationships between CaxP and PTH with cardiac and sudden death were also found

(30).

The association between elevated serum phosphorus and mortality has been shown in

dialysis patients; however this evidence is not as widespread with pre-dialysis CKD. A study

conducted by Kestenbaum et al. (2005) aimed to associate elevated serum phosphorus with

increased risk of death in patients with pre-dialysis CKD (31). Data was collected from the U.S.

Veteran’s Affairs Consumer Health Information and Performance Sets, and 6730 patients with

CKD were involved in the study (31). The risk of mortality was significantly increased with

serum phosphorus levels greater than 1.13 mmol/L (31). The adjusted Hazards Ratio (HR)

(95%CI) was found to be 1.34 (1.05-1.71) for serum phosphorus between 1.29-1.45 mmol/L,

HR was 1.83 (1.33-2.51) with 1.45-1.62 mmol/L and 1.90 HR (1.30-2.79) with serum

phosphorus ! 1.62 mmol/L. Hyperphosphatemia to this extent can be commonly found

amoungst CKD patients; particularly within our renal disease clinic at St. Michael’s Hospital

(SMH), as 36% of screened patients had serum phosphorus levels greater than 1.35 mmol/L.

The Kestenbaum study is observational and therefore doesn’t show whether elevated serum

phosphorus levels cause the effects associated with mortality or whether elevated serum

phosphorus levels are a passive marker for these effects (31). Further clinical trials are required

to show whether modifying phosphorus levels with diet and medications can improve mortality

risk in CKD patients (31).

There are numerous possible consequences, direct and indirect, of having an elevated

serum phosphorus level; as stated by Block and Port (2000):

these consequences include increased CaxP, parathyroid gland hyperplasia, increased PTH levels, coronary artery calcification, death from coronary artery disease and sudden death, conduction defects, arrhythmias, mitral and aortic valve calcification, peripheral vascular calcification, pulmonary/periarticular calcification, calcific uremic arteriolopathy, calciphylaxis, hypertriglyceridemia, hypercholesterolemia, and myocardial fibrosis.

11

The consequences of hyperphosphatemia that are of greatest concern and mentioned most

frequently in the literature, which will be outlined below, include secondary

hyperparathyroidism, renal osteodystrophy, soft tissue calcification, and the cardiovascular

complications resultant from calcification.

2.3.2.1 Secondary hyperparathyroidism

The main characteristic of secondary hyperparathyroidism is hyperplasia of the gland

and an increased synthesis of PTH, which typically occurs as a result of accumulation of

phosphorus in the body, hypocalcemia, increased calcium-phosphate product, and reduced

synthesis of vitamin D (20). Secondary hyperparathyroidism is thought to initially occur as a

result of low renal calcitriol production in the early stages of CKD. As CKD progresses,

hyperphosphatemia becomes the main factor in the progression of secondary

hyperparathyroidism (32). It is typical for symptoms of secondary hyperparathyroidism to

present after persistent hyperphosphatemia along with insufficient calcitriol therapy (32).

Secondary hyperparathyroidism is extremely difficult to reverse, and therefore early

management, especially in the pre-dialysis period, of hyperphosphatemia is crucial to prevent its

occurrence (22,28). Improved control of hyperphosphatemia is crucial for the management of

secondary hyperparathyroidism; additionally, calcitriol therapy effectiveness may be reduced if

hyperphosphatemia is not well managed (32).

2.3.2.2 Renal osteodystrophy

High levels of PTH results in high-turnover bone disease; where bone mineral resorption

occurs and osteoclastic activity is stimulated. The new bone that is then built consists of a

disordered collagen due to the low levels of calcium and high levels of phosphate in CKD

12

(13,20). This effect on the skeletal system may be silent until a minor injury, such as a fracture

of the hip, wrist or arm occurs, and it becomes a pathological fracture (20). Nephrologists

previously focused primarily on renal osteodytrophy that occurs with hyperparathyroidism as

the most detrimental complication of hyperphosphatemia; however, Block & Port (2000)

suggest a shift in the area of concentration in that uremic calcification, cardiac death and

vascular calcification should be the primary focus.

2.3.2.3 Soft tissue and vascular calcification

Crucial uremia-related risk factors for soft tissue calcification, cardiac injury and death

include elevated serum phosphorus, PTH and calcium phosphate product (CaxP) (33).

Hyperparathyroidism results in an elevated CaxP which is deposited in bone or tissues (34). As

calcium phosphate product is formed, hypocalcemia occurs (13). High serum phosphorus and

elevated CaxP result in increased incidence of cardiac, visceral (organs such as the kidneys and

lungs) and peripheral vascular calcification (12,34). The prevention of hyperphosphatemia and

elevated CaxP may help prevent bone and vascular disease (34) .

2.3.2.4 Cardiovascular complications

Mechanisms

End-stage renal disease patients on hemodialysis are most likely to experience a cardiac-

incident related death, as the rate of cardiovascular disease within this population is far greater

than in the general population (35). The relative risk of death in hyperphosphatemic

hemodialysis patients from CAD is 1.41 (p<0.0005) (30). It is thought that likely, patients who

have already experienced cardiac damage and have poor long-term phosphate control are at an

increased risk of calcification and cardiac death (12). Hyperphosphatemia independently

increases cardiovascular mortality and morbidity; elevated phosphorus may increase vascular

13

calcification and smooth muscle proliferation and therefore aggravate the effects of coronary

atherosclerosis (12). It appears to researchers as though atherosclerotic calcification is a process

very similar to that of bone formation; cells and proteins with osteoblastic differentiation

capabilities and that are involved with bone formation and calcification have been found in

coronary arteries with atherosclerotic plaques (36).

Hyperphosphatemia may also be responsible for increasing cardiac risk as it modifies the

morphology of coronary plaques and affects the heart structure through thickening of the wall of

cardiac arterioles (37). In addition to poor long-term phosphate control, a previous history of

arterial hypertension, diabetes, oxidative stress, anemia, secondary hyperparathyroidism,

inflammation, and hyperhomocystinemia are factors that may contribute to cardiovascular

damage and atherosclerosis (4). High CaxP has also been found to result in coronary artery

calcification (34). Valvular calcification, which can be evaluated by echocardiogram, was found

more frequently in dialysis patients versus normal patients (38). Calcification resulting in

damage to normal cardiac tissues can lead to abnormal conduction and arrhythmia, left ventricle

dysfunction, aortic and mitral valve stenosis and regurgitation and complete blockage of the

heart (12).

Evidence of calcifications in patients

Electron-beam computed tomography (EBCT) has found a remarkably high rate of

coronary artery calcification in patients on HD, and this contributes largely to the atherosclerotic

plaque burden facing these patients (2). Block & Port (2000) suggested that the data shows that

elevated phosphate, calcium-phosphate product and PTH contribute to the mortality of dialysis

patients through coronary artery disease (CAD) and sudden cardiac death. Additionally, it was

shown that the severity of coronary artery calcification (CAC) in patients starting hemodialysis

is a predictor of long-term survival (3).

14

Looking at the magnitude of coronary calcification in CKD patients new to dialysis, it

was found that 34% of patients had coronary calcification scores greater than the 90th percentile

for age and sex (39). Interestingly, subjects with diabetes had significantly more coronary artery

calcification versus those without diabetes (p=0.01) and also significantly more mitral valve

calcification (p=0.04); however this trend was not seen in aortic calcification (39). Coronary

artery calcification and aortic calcification seemed to occur together in both diabetic and non-

diabetic subjects (p<0.0001) (39). Thus this study shows that calcification is occurring in CKD

prior to dialysis initiation in the coronary artery, aorta and mitral valve; however, greater

calcification has been found in patients who are long-term dialysis users (39). Patients with

diabetes, who are also more likely to have pre-existing CAC, appear to have greater calcification

(39); and diabetes is presently the leading cause of CKD.

Evaluations of coronary artery calcification CAC in pre-dialysis patients occur less

frequently. A study using high speed spiral computed tomography (CT) to evaluate CAC in

patients with pre-dialysis CKD compared to controls without CKD found CAC in 40% of

patients with CKD and only 13% of those without CKD (40). The CKD patients presenting

with CAC were more frequently found to be greater than 50 years of age and presented with

calcification in more than one coronary artery; no differences were found in CKD patients with

CAC versus those without in GFR, phosphorus, calcium or iPTH levels; all of which are

commonly thought to contribute towards calcification (40). A greater magnitude of calcification

existed in patients with CKD versus controls, and this with the increased occurrence of

calcification shows a link between CKD and CAC (40).

Tomiyama et al. (2006) completed a study looking at coronary calcification and related

factors in pre-dialysis patients with stage 2-4 kidney function, by evaluating clinical profiles,

laboratory results and multislice computed tomography (CT) scans to determine the coronary

artery calcification score (CACS). CACS greater than 0 AU represented the presence of

15

calcification and CACS greater than 400 AU represented severe calcification (41). Of the

ninety-six patients who participated, 64% had calcification, and of those, 23% presented with

severe calcification (41). In addition, the sample was stratified based on their stage of CKD, and

they found calcification in 69% of those with stage 2 CKD, 61% of those with stage 3 CKD and

in 66% of those with stage 4 CKD (41). The researchers also looked at the significant

differences between the patients who presented with calcification and those that didn’t, and it

was revealed that those with calcification, among other characteristics, had higher levels of PTH

(41). The increased PTH could potentially be related to a need for greater dietary phosphate

control for prevention of cardiac complications as the participants may have had elevated

phosphorus levels that caused the high PTH, which may have been masked by this increased

PTH secretion.

The need for phosphorus control prior to initiation of dialysis was demonstrated.

2.3.2.5 Atherosclerosis and dislipidemia

Hyperphosphatemia and hyperparathyroidism have been shown to suppress lipoprotein-

regulating enzymes and have an effect on arterial wall thickening (12,42). This results in an

unfavorable lipoprotein profile of reduced high-density lipoprotein (HDL) and increased

intermediate-density lipoprotein (IDL) levels; this lipoprotein profile is associated with arterial

wall sclerosis (12,42).

2.3.2.6 Summary

When looking at the risks associated with elevated phosphorus, CaxP and PTH, it is

evident that the most significant concern is the potential for cardiac calcification, soft tissue

calcification, and cardiac death (2). Since hyperphosphatemia and elevated CaxP are associated

16

with a greater risk of mortality in patients on dialysis, it is necessary to prevent and manage

these elevated levels to possibly reduce the risk in patients with CKD (20).

2.4 Hyperphosphatemia Management

The Canadian Society of Nephrology (CSN) (43) and the National Kidney Foundation’s

Kidney Disease Outcomes Quality Initiative (KDOQI)(44) have developed clinical practice

guidelines for the management of bone metabolism and disease in chronic kidney disease which

detail the clinical management of hyperphosphatemia. The National Kidney Foundation began

the Kidney Disease Quality Outcomes Initiative (KDOQI) program in 1997, which provides

health professionals with guidelines and target values to be achieved in chronic kidney disease.

Elevated serum phosphorus can be managed through phosphate binders, dialysis, and dietary

restriction (12).

2.4.1 Phosphate Binders

Dietary phosphate restriction is often challenging for patients, and often not sufficient on

its own to control blood phosphorus in hyperphosphatemic CKD patients (12). Patients with

CKD and whose GFR is less than 20-25% often require phosphate binders (12). Phosphate

binders are consumed prior to a meal; with the intention of binding dietary phosphorus to

prevent it’s absorption in the intestine and increase fecal excretion of phosphorus. In the

development of the KDOQI guidelines on the use of phosphate binders, studies looking at the

effectiveness of phosphate binders were evaluated (45). Prospective, controlled studies of the

efficacy of phosphate binders in stage 3 and 4 CKD did not exist, however studies of this nature

were completed in stage 5 CKD, or ESRD (45,46). All of the phosphate binders tested were

shown to reduce serum phosphorus to some extent. One gram of calcium carbonate, the most

17

frequently consumed phosphate binder, binds approximately 39 milligrams of phosphorus in the

intestine (45).

Phosphate binders are more effective when dietary intake is less than 1000mg/day; once

intake exceeds 1500mg/day the effect of the binders markedly decreases (12). Phosphate binder

dosage is dependent upon the patient’s serum phosphorus and the size of meals consumed (12).

The goal of phosphate binder therapy is to maintain levels of serum phosphorus within target

without causing side effects (46).

Aluminum hydroxide and aluminum carbonate were frequently used binders in the

1970s, however the excess aluminum that was absorbed was found to cause dialysis dementia,

osteomalacia, muscle weakness and anemia (47). Calcium-based phosphate binders are widely

used; however there has been increasing evidence that suggest the absorption of large doses of

calcium could lead to hypercalcemia (27). Sevelamer is a non-absorbed binder, which is a

cutting edge development, that does not contain aluminum or calcium and is currently

increasing in popularity (12,48). Although sevelamer has its benefits, and may decrease the

occurrence of hypercalcemia, it is too premature to abandon calcium-based phosphate binders,

as the calcium binders have been found to have better serum phosphorus and CaxP control and

cost less than sevelamer (49).

Calcium-containing phosphate binders should be increased gradually until serum

phosphorus levels are controlled (12). KDOQI guidelines specify that the load of calcium from

calcium-containing binders should be less than 1.5g/day of elemental calcium (46). At St.

Michael’s Hospital, the binder that is most frequently used is calcium carbonate, often in the

form of Tums®.

18

2.4.2 Dialysis

Dialysis is an additional means for reducing serum phosphorus in patients with end-stage

renal disease (ESRD), in addition to dietary restriction and phosphate binders. Patients whose

kidneys have failed, and are thus on dialysis, have the highest phosphorus levels. The

effectiveness of dialysis however is limited due to insufficient phosphate removal; phosphate

resides in the intracellular compartment and thus is challenging to access during dialysis (50).

When looking at the kinetics of phosphorus during dialysis, DeSoi & Umans (1993) found that

serum phosphate fell during the first hour of HD; however, serum levels began to rise again

towards the end of HD and 4 hours after dialysis the phosphate level was back up to what it had

been pre-dialysis; this occurrence is also known as post-dialytic rebound (PDR). Phosphate

removal continued throughout dialysis, however serum phosphate levels did not decrease for the

entire dialysis treatment (51). Thus phosphate is thought to be mobilized from a pool besides

extracellular fluid to lead to this increase (51). It has been found that nocturnal hemodialysis is

more effective at removing phosphorus, and patients on this regimen are often permitted to have

a less restrictive diet and may not need phosphate binders (52). Nocturnal dialysis, in the study

by Mucsi et al., was carried out for eight to ten hours per night, six to seven times a week (52) .

Mucsi et al. (1998) compared nocturnal HD to conventional HD and found that both methods

reduced serum phosphate; however, the rebound of phosphorus two hours after the cessation of

nocturnal HD barely reached statistical significance; thus suggesting a greater opportunity of

this method for balancing phosphorus. Thus it is clear that dialytic phosphorus removal via

conventional hemodialysis in ESRD is not adequate alone.

2.4.3 Dietary phosphate restriction

The recommendations of the Canadian Society of Nephrology (43) and the Kidney

Foundation Kidney Disease Outcomes Quality Initiative (KDOQI)(44) require patients living

19

with chronic kidney disease between stages 3 to 5 and who experience elevated serum

phosphorus levels to restrict their dietary intake of phosphorus to between 800 and 1000 mg.

KDOQI suggests that patients with stage 3 and 4 CKD maintain their serum phosphorus

levels between 0.87 mmol/L and 1.49 mmol/L; and stage 5 CKD patients maintain levels less

than 1.78 mmol/L (53). These guidelines also follow those recommended by the Canadian

Society of Nephrology’s Hemodialysis Clinical Practice Guidelines (43). As mentioned

previously, CKD patients with persistent hyperphosphatemia that cannot be controlled by diet

alone are prescribed to take phosphorus binder medication in combination with dietary

restriction.

2.4.3.1 Phosphorus food sources

Food items rich in phosphorus include meat, fish, poultry, milk and eggs (54). Other

sources of phosphorus include organ meats, peas, beans, lentils, soy products, bran, all bran

cereals, and coarse grain products (12). Processed foods, such as restructured meats, processed

cheeses, instant products, refrigerated bakery products and beverages contain phosphorus

additives (12,55), of which patients are often not aware.

2.4.3.2 Phosphorus Additives

Manufacturers are not required to put phosphorus information on food labels, and

therefore it can be quite difficult to determine which foods contain these phosphorus additives

and the quantity of these additives within the food (55). Murphy-Gutekunst (2005) surprisingly

discovered, when looking for phosphorus levels of common beverages, that 12 ounces of Nestea

Cool iced tea has more phosphorus than 4 ounces of milk. Other barriers to receiving

phosphorus information on food products includes the lack of nutrition information provided to

customer service representatives, nutrition analysis information is often confidential, companies

20

may change their product formulation frequently but are only required to report nutritional

content once per year, and nutrition facts on websites are not always accurate (56,57).

Additionally, fresh meat products that are enhanced with additives to improve its appearance on

the shelf are hidden sources of phosphate and use phosphate salts in unknown quantities without

including that information on the label; thus it is very difficult to obtain phosphorus information

on these products (58). A study looking at the accuracy of nutrient databases with respect to

chicken products found that 35 of 38 (92%) chicken products contained phosphorus additives

(59). The chicken products reviewed included both boneless chicken breasts and processed

chicken products (59).

About 65% of naturally-occurring dietary phosphorus is absorbed; however, almost

100% of phosphoric acid and various polyphosphates that are used as additives are absorbed

(1,15,60). Thus these food sources of phosphorus can be a significant contributor to

hyperphosphatemia and make it difficult to maintain a reduced intake level (60).

Phosphorus-additive containing foods such as beverages, meat products, cereal and

snack bars, flavored waters, and frozen entrees, are items which are commonly consumed either

due to convenience or the low-cost of these processed items (61). Dietary habits are changing

and processed foods are being consumed more readily (62); this expands the role of the dietitian

to provide patients with education regarding the phosphorus content of processed foods. In

1990, 470mg/day of dietary phosphate intake in Americans adults was attributed to phosphorus-

containing food additives, and this number has likely grown with the increased use of processed

foods (62).

Sullivan et al. (2007) found that the expected quantity of phosphorus in chicken

products, based on the information in nutrient composition tables, were lower than the actual

quantities found with laboratory analyses (59). For example, in breaded chicken breast strips,

the actual phosphorus content was an average of 84mg/100g higher than was expected based on

21

data from the United States Department of Agriculture National Nutrient Database for Standard

Reference (59). Thus the role of the dietitian in educating patients about phosphorus additives

within processed foods becomes more challenging as the accuracy of the nutrient database

phosphorus content is unknown.

A study looking at compatibility of fast-food entrees and side dishes with the renal diet

found that only 16% of the entrees initially deemed acceptable based on traditional renal

guidelines, were free of phosphorus-containing additives (63). The phosphorus contents initially

used to determine the acceptability of the food items were based solely on naturally-occuring

phosphorus, and the presence of phosphorus additives resulted in items becoming unacceptable.

The most common foods which were deemed acceptable based on renal guidelines but that

contained phosphorus additives were baked products, chicken products and ham products (63).

The side dishes also were similar, in that only 17% of the 37 side dishes initially deemed

acceptable were free of phosphorus additives (63). Thus it is clear that a large proportion of fast

food items contain phosphorus additives, which likely has a large impact of the dietary

phosphorus load of patients who frequently consume fast food.

2.4.4 Evidence supporting dietary phosphate restriction

Studies involving rats induced with renal insufficiency have shown that phosphorus

depletion or restriction has a protective effect against chronic renal disease progression and can

prevent hyperparathyroidism (26,64).

Rats which received a 5/6 nephrectomy and fed a normal diet for 30 days, were divided

into two groups matched and paired for body weight and serum creatinine (26). Animals of one

group were fed a phosphate deplete diet and the other group a normal phosphate diet; diets were

otherwise similar (26). Serum phosphate was significantly higher in normal phosphate diet rats

versus phosphate deplete rats at weeks 6, 8, 10 (p<0.001), week 12 (p<0.005) and week 14

22

(p<0.002) (26). At weeks 12 & 14, serum creatinine was significantly higher in the group fed

the normal phosphate diet (p<0.025 and p<0.05, respectively), and creatinine clearance was

significantly lower in this group as well at weeks 12 and 14 compared to the phosphate deplete

rats (p<0.001 and p<0.005, respectively); thus indicating that there was greater progression in

renal disease in this group (26).

Uremic 5/6 nephrectomized rats were randomized to either a low phosphorus diet group

or a high phosphorus diet group for two months, and compared to two groups of control normal

rats receiving the same two diets (64). Serum phosphorus was significantly higher in the uremic

rats fed the high phosphorus diet compared to the three other groups (p<0.01) (64). As well,

serum PTH was significantly higher in uremic rats fed the high phosphorus diet compared to

uremic rats fed the low phosphorus diet (p<0.001) (64). There were no differences in PTH in

the normal rats (64). Parathyroid gland weight was significantly higher in the group consuming

the high phosphorus diet versus the group consuming the low phosphorus diet uremic rats

(p<0.001) (64); thus indicating gland hyperplasia.

A study conduced with Thy1 rats, whose renal disease mimics that of IgA nephropathy

and results in proteinuria, hypertension and a decline in renal function, were matched on the

basis of serum creatinine to groups and then fed one of six diets, that varied in protein and

phosphorus content, for 13 weeks (65). The diets consisted of normal or low phosphorus levels,

matched with one of either protein level; normal (16.9%), low (12.6%) or very low (8.4%)

protein (65). The analysis of the time course of serum creatinine in the rats showed that the low

phosphorus diet, regardless of the protein content, had significantly lower levels of serum

creatinine at week 13 (p<0.05) and thus had a significant positive effect on reducing the

progression of renal disease (65). As well, PTH levels were significantly lower in the low

phosphorus diet groups than the normal phosphorus diet groups at weeks 2 and 13 (p<0.05).

Histopathological results looking at the lesions within the kidney at week 13 found the same

23

protective effect of the low phosphorus diet in all low phosphorus diet groups except for the

normal protein/low phosphorus group (p<0.05) (65). Interestingly, rats fed a normal phosphorus

but very low protein diet showed the beneficial effects biochemically (PTH) and histologically;

thus very low protein diets may also be beneficial (65) . Dietary phosphorus restriction was

protective in CKD progression independent of protein, and thus this is an important

modification necessary in the treatment of CKD within the rat model (65).

The evidence within humans has not been demonstrated as conclusively as that within

animals. The results of four cross-sectional studies in human models were used by the Work

Group of the National Kidney Foundation in the United States to base the clinical practice

guidelines of maintaining serum phosphorus levels within the targets of 0.87mmol/L and 1.49

mmol/L for stage 3 and 4 CKD and of 1.13 to 1.78 mmol/L in stage 5. These studies found

associations between elevated serum phosphorus and poor outcomes including mortality

(29,53,66-68).

2.4.5 Protein restriction to delay the progression of CKD

The Modification of Diet in Renal Disease (MDRD) study assigned patients on the basis

of GFR to diets that differed in protein content, and each eating pattern had differing goals for

phosphorus within the diet as well (69). Two separate studies were completed, one comparing

low-protein versus usual-protein and the other comparing low-protein to very low-protein. In

the first study, patients on the low-protein had an initial greater decline in GFR in the first four

months but then a slower decline thereafter, compared to the usual protein group. In the second

study there was a trend indicating improvement in the decline in renal function in the very low-

protein group compared to the low-protein group; however this did not result in a delay to renal

failure or death (69). Overall, a protective effect in renal decline was seen in both the low and

very-low protein groups, thus indicating a potential protective effect of low protein diets in CKD

24

(69). In both studies, the phosphorus content of processed foods was not taken into

consideration.

There is continued concern about the recommendation of low protein diets to this group

secondary to the risk of malnutrition. Therefore, this theory regarding the potential protective

effect of low protein diets on kidney disease progression has been widely researched and

disputed, and the debate on this continues to this day (4,25,70). These findings, however, fueled

speculation of the possible positive effect of phosphorus restriction in CKD progression.

2.5 Effectiveness of Educational Interventions in CKD

2.5.1. Evaluating effectiveness of education

According to Kirkpatrick there are four levels of evaluating the effectiveness of

continuing professional education (71). These consist of level one - perception and opinion of

data, level two – knowledge, skills and attitudes (competency), level three - performance data,

and level four – outcome data (71). To evaluate the effectiveness of dietary education, the same

principles of evaluation can be applied. To determine the group’s perception and opinion of

data, a satisfaction questionnaire is typically used. To identify if change in knowledge or skill

has occurred, one would typically provide an objective set of questions before the instruction

takes place, and administer the same questions after education to identify if learning has

occurred. Level three is evaluated by looking at whether the audience has incorporated what

they have learned into their activities (71). Evaluating outcome data would require determining

whether the education has had an impact on health outcomes (71).

The levels of evaluating the effectiveness of education were integrated within the study

design to determine the effectiveness the Phosphorus Point System Tool©.

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2.5.2 Phosphatemia reduction with intensive dietary education in hemodialysis

Studies investigating the effects of dietary phosphorus education in lowering serum

phosphorus levels have been completed solely in dialysis patients and are summarized below.

An additional 20 to 30 minutes of dietary phosphorus education based upon the patients’

serum phosphorus level was provided once monthly for 6 months to hyperphosphatemic,

hemodialysis patients in a study done by Ford et al (2004). Patients were deemed

hyperphosphatemic if they had mean serum phosphorus greater than 1.94 mmol/L over 3 month

(18) The patients’ improvement in knowledge-level was assessed via before-and-after tests,

which revealed that there was a significant increase in the average test scores in the group

receiving additional education each month compared to the control group (p=0.005) (18). The

control group received routine care (18). Mean serum phosphorus and mean CaxP significantly

improved in the intervention group from preintervention to postintervention (p=0.0001) (18) .

As well, mean serum phosphorus and mean calcium-phosphate product of the intervention group

were significantly lower than those of the control group after the 6-month intervention period (p

<0.001) (18). Educational tools used in the 20-30 minutes of teaching included posters,

handouts, puzzles and a serum phosphorus level tracking tool (18). This research supports the

concept that more intensive phosphorus education, in the form of spending extra one-on-one

time with the patients on a monthly basis can improve phosphorus control, as well as patient’s

knowledge about phosphorus and risks of hyperphosphatemia. Thus an important factor in this

research is the time the dietitians spent with the patients, which may not be practical in typical

working environments.

De Brito Ashurst et al. (2003) found that patients in the intervention group of their study

had a significant reduction in their mean serum phosphorus levels in the 3 months

postintervention (p=0.02). The study provided hyperphosphatemic patients in the intervention

26

group with a one time one-on-one teaching by a dietitian of a more intensive education tool to

improve their phosphorus balance knowledge (24). The tool provided patients with dietary,

medication and lifestyle advice and consisted of a booklet, a medication record chart and a

refrigerator magnet. The booklet explained phosphate and calcium metabolism via a cartoon,

described the role of dialysis, phosphate binders and dietary restriction in management and

emphasized the importance of compliance. The control group received standard dietary

education. Both patient groups were provided with a medication record chart, wherein they had

to report phosphate binder and vitamin D medications consumed during a one-week period (24).

Since the researchers attempted to improve phosphate binder compliance, it is unknown how

much of the improvement is due to diet or medication compliance (24). However, once again,

increasing the knowledge of the patients about phosphorus and hyperphosphatemia via

innovative means may have an impact on improving phosphorus control (24).

An 8 week intervention study was completed with normophosphatemic and

hyperphosphatemic hemodialysis patients; the hyperphosphatemic group was provided with

dietary education regarding lowering phosphorus intake but maintaining protein intake, via

phosphorus-protein ratios (23). The control group did not receive dietary phosphorus education.

Three day food records and serum blood values revealed that after 8 weeks, with the provision

of more intensive dietary education, protein intake was unchanged but mean 3-day phosphorus

intake was reduced by more than 100mg, calcium phosphate product decreased significantly (p

<0.05) and serum phosphorus decreased, however the decrease did not reach statistical

significance (23) . The study did not capture whether the patients consumed phosphorus

additives, and this quantity of phosphorus consumed would not have been captured by the

dietary analysis software. The short duration of 8 weeks may not have been a long enough time

period for participants consistently change dietary intake which would thus relate to a significant

27

decrease in serum phosphorus. Nutritional education did appear to have a significant impact on

reducing phosphorus intake but not serum phosphorus concentration (23).

A study looking at the effectiveness of a newly developed educational patient

compliance group program versus standard individual counseling on improving serum

phosphorus levels in patients receiving hemodialysis for one year, found no significant

difference between the groups in serum phosphorus levels (72). However, the phosphorus levels

in both groups declined over time; mean serum phosphorus levels significantly decreased from

pretreatment period to the treatment period and posttreatment period. This supports the idea that

innovative dietary education lowers serum phosphorus levels, although this is not dependent of

the type of counseling being provided (72). The researchers determined that choosing the

educational intervention that supports the patient and his or her style of learning is the best

method to encourage better phosphorus control (72) .

A study conducted to determine the effect of an educational intervention on

hyperphosphatemic dialysis patients provided patients with a one time one-on-one educational

session, which lasted for 15-20 minutes, using a personalized osteodystrophy tool and a

phosphate binder diary which was to be filled-in for three weeks (73). A Phosphorus

Knowledge Assessment Tool was developed for this study to measure phosphorus knowledge,

and was administered at baseline and three weeks after the education was provided. Patients

were used as their own controls. There was no significant difference in mean serum phosphorus

three months after the education. The scores of the knowledge test improved significantly after

teaching was administered (p<0.01). Patients’ knowledge levels may have improved; however

improved knowledge doesn’t necessarily translate into action, which may possibly explain the

lack of change in serum phosphorus levels. As there was no control group, a Hawthorne effect

could potentially be responsible for the improved knowledge-level, as the patients were aware

they would be tested on their learning and could have possibly strived for greater learning than

28

may be typical in a clinical setting (73). The type of education provided, in the form of a one-

time teaching using handouts, may have had an impact on the lack of improvement as well.

In another study, fifty hemodialysis patients were evaluated via a questionnaire to assess

pre-education phosphorus knowledge, and serum measures were collected (74). Thereafter, a

patient education program was administered by a nephrology nurse which was focused on

hyperphosphatemia and diet control. The patients rewrote the questionnaire after receiving the

education, and if a perfect score was not attained, the education was provided again. This was

repeated until a perfect score was achieved. Serum measures were completed one month after

education. Serum phosphorus was significantly lower one month after the education was

provided (p=0.034); the same was found with CaxP (p=0.022) (74). The duration of the effect

of the teaching on lowering serum phosphorus was assessed and three months after education it

was found that 97.2% of patients retained phosphate levels lower than those prior to the teaching

(74) This is indicative that education which takes a different form can result in positive

outcomes.

A study that involved a phosphate management protocol for hemodialysis patients,

which was devised by renal dietitians and renal pharmacists, resulted in significantly greater

reductions in serum phosphorus compared to those receiving standard treatment (p=0.03) (75).

The protocol enabled dietitians and pharmacists to modify the patients’ medications without

needing to consult a renal consultant, as per the algorithm that was devised (75). Dietary

recommendations were provided at monthly study visits by the dietitian and were given

individually to each patient in the form of both verbal education and a choice of written

material; either a low-phosphorus diet booklet or an individual diet plan (75). Dietary data was

not collected. The researchers concluded that the increased time the dietitians and pharmacists

devoted to the care of these patients, may have contributed to the serum phosphorus

29

improvement (75). Thus it appears that when it comes to improving phosphate control, patients

benefit from increased attention and focus on their phosphorus levels.

When looking at the effects of providing more frequent, monthly dietary phosphorus

education for six months to hemodialysis patients, compared to the standard education that is

provided once every six months, a group of British researchers found that mean serum

phosphorus levels decreased significantly within the intervention group from baseline to month

3 (decrease from 2.05±0.48 mmol/L to 1.80±0.48 mmol/L, p=0.003) (76). The more frequent

education was provided in the form of individualized strategies for modifying their diet, using

motivational counseling, negotiation, reminders, reinforcements, supportive care and written, as

well as verbal, instruction. Despite the significant decrease in serum phosphorus seen from

baseline to month 3 in the intervention group, there was no significant change in phosphorus

from month 3 to month 6 in this group. As well, upon completion of the study, there was no

significant difference in serum phosphorus between both groups at 3 months and 12 months

later. The calcium phosphate product declined in both study groups, however a significantly

lower CaxP was seen in the intervention group compared to the control group at month 3

(p=0.007) (76). The researchers speculated whether the difficulty of a low phosphorus diet itself

contributed to the lack of positive results.

See table 2.0 for a comparison of the various educational intervention studies and the

effect on serum phosphorus levels in patients on hemodialysis.

2.5.3 Phosphatemia reduction with intensive dietary education in peritoneal dialysis

A preliminary study was completing using the Phosphorus Point System Tool© which

evaluated the effect of the tool on improving dietary adherence and satisfaction with outpatient

peritoneal dialysis (PD) patients (77). Ten patients who had been on PD for at least six months

were selected to use the tool for one month. The study had a prospective, interventional,

Table 2.0 – Summary of Studies Examining Serum Phosphorus in Response to Dietary Intervention in Hemodialysis Patients

Researcher Ford (2004) de Brito Ashurst (2003)

Schlatter (1998) Sun (2008) Yokum (2008) Morey (2008)

Intervention

20-30 minutes dietary phosphorus education per month for 6 months

one time one-on-one teaching with an intensive educational tool

one time one-on-one teaching for 15-20 min with an osteodystrophy tool

Individual education program coupled with repeat questionnaire

Phosphate management protocol provided by dietitians and pharmacists

Monthly dietary education for 6 months

Serum phosphorus (mmol/L)

Within group 2.20±0.23 to 1.68±0.39 (p=0.0001, n=32)

Within group 1.96 to 1.60 (p=0.02, n=29)

Within group 2.06±0.40 to 2.00±0.36 (p=0.50, n=29)

Within group 2.38±0.39 to 2.16±0.63 (p=0.034, n=50)

Between groups at week 16 2.07±0.25 to 1.81±0.54 p=0.03, n=31

Within group at 3 months 2.05±0.48 to 1.80±0.48 (p=0.003, n=30)

31

before-and-after study design which determined adherence to the tool by measuring serum

phosphorus levels, analyzing repeated 24-hour recalls, and assessed satisfaction with the tool

versus the standard choose/avoid handout by using a face-validated 23 item questionnaire

adapted from that used in Modification of Diet in Renal Disease study. The participants

received weekly telephone calls to ask if they had any questions or concerns or had found any

foods that were not listed in the tool and required assistance. It was found that there was a

significant decrease in serum phosphorus levels from 1.65 to 1.45 mmol/L (p=0.019) and the

calcium phosphate product decreased from 3.92 to 3.22 (p=0.008). Two 24-hr recalls that were

completed one week apart were averaged; the first was conducted via the telephone and the

other face-to-face. There was a non-significant decrease in dietary phosphorus intake following

the use of the tool for one month (p=0.16). There was no significant difference in satisfaction

scores when comparing the PPS to the Choose/Avoid handout; however, this may be attributed

to the idea that some patients prefer the Choose/Avoid tool as it simplifies food choices. Further

research suggestions stemming from this study included facilitating a longer term study using a

randomized control trial format to allow comparison to a control group and developing

phosphorus point to binder ratios for patients.

2.5.4 Impact of patients’ knowledge level on outcomes

Dietitians may not consider the idea that patients with limited education may have a

limited understanding of the concepts discussed during their sessions, and this may have an

impact on their serum levels. A 10 question survey, with a grade 5 reading level, was provided

to 117 hemodialysis patients, and demographic information such as level of education

completed was collected. The survey consisted of 5 questions about phosphorus and 5 questions

surrounding patient attitudes and beliefs (34). The researchers identified that patients with a

CaxP > 55 mg/mL2 scored lower on the survey and were significantly less likely to have had

32

university-level education (34). Monthly, and often weekly counseling was provided to patients

using written and pictorial handouts and bulletin boards with reading levels ranging from grade

2 to 6 (34). Despite this, the study found that the majority of patients were unaware of the basic

concepts surrounding phosphorus and CaxP (34). A suspected barrier to compliance was the

patient’s poor level of comprehension surrounding phosphorus, and the dietitians’

overestimation of their patients’ level of understanding during the counseling sessions (34).

Patients receiving once-monthly dietary instruction were found to have a poor

knowledge of dietary phosphorus content compared to other nutrients important in kidney

disease, such as potassium, sodium and protein; despite the majority of patients having adequate

health literacy (78). This was assessed via a multiple choice questionnaire consisting of 25

questions; 15 of which were about phosphorus and the remaining 10 questions covered the

aspects of protein, sodium and potassium dietary modifications (78). This appears to be a

common occurrence in kidney disease patients, and thus more innovative means for providing

dietary phosphorus education are recommended (78).

A study looking at factors that are associated with compliance to renal diets in patients

aged 50 and older found that the phosphorus knowledge-level of the participants was positively

correlated with compliance (79). Among other results, 84.3% of non-compliant patients

(p=0.0002) agreed with the statement “my special diet has no effect on my health”, revealing the

lack of association identified by non-compliant patients with regards to their renal diet and

health outcomes (79) . Therefore, it is important for renal dietitians to teach patients about the

health effects of a renal diet, and the detrimental effects of non-compliance. Renal patients are

more likely to be compliant if they are aware of the need for compliance, are educated

sufficiently about their diet needs, have a good attitude towards compliance and have a

supportive environment (79).

33

2.5.5 Dietary adherence and satisfaction with phosphorus restriction

Compliance to a phosphorus restriction is often challenging for renal patients, in that

there are numerous food sources of phosphorus, and the patients often have many other dietary

guidelines which to follow; including sodium, potassium and/or fluid restrictions. Renal

patients have also been found to be confused and frustrated when following a renal diet, as it

often contradicts the typical healthy diet they may have been following for other co-morbidities;

in terms of fibre, and fruits and vegetables (80). Patients themselves play a very important role

in their success in following a renal diet, as it depends greatly on their ability and willingness to

follow dietary restrictions and medication schedules (18). It is often difficult to ensure patients

with renal disease comply with their dietary restrictions, as they often have numerous co-

morbidities, social and familial conditions and psychological aspects that make them ill-

disposed to following the many restrictions (23). Adherence is also influenced by the quality of

the relationship between the patient and health care provider, patient attitudes about benefits of a

renal diet, and the counseling and teaching techniques used with the patient (81). It is said that

dietary adherence is typically less well sustained compared to taking medications or attending

appointments due to the challenges of the disease and the need for dietary modulation

throughout its course, as well as the social consequences of making dietary changes (81).

Nephrology patients interviewed about their views of their renal diet, stated that they knew what

was best for them in terms of their dietary intake, and despite receiving dietary advice from a

dietitian or nurse, would self-monitor their diet and make adjustments based on what they felt

they were tolerating, rather than focusing on the dietary advice (80). As well, when

nonadherence occurs it can be intentional or unintentional; however, nonadherence could lead to

hospitalization, premature initiation of dialysis, degenerative changes and many more

34

detrimental consequences such as metastatic calcification and secondary hyperparathyroidism

(81).

In a study looking at the factors associated with improved dietary adherence in renal

patients, the program the patients were following focused on emphasizing long-term eating

behaviours rather than restrictions (82). The researchers identified that these dietitians provided

more frequent encouragement and praise rather than instruction; and thus patients’ self-esteem

and motivation increased when they felt as though they were achieving success on their own

(82) . Psychosocial factors that were discovered to be associated with improved dietary

adherence included the possession of greater knowledge and skills, a more positive attitude

about the eating pattern, having increased social support, the attitude that the eating pattern

interfered less with social activities, and higher overall satisfaction with the eating pattern (82) .

The behavioural factors that were identified in patients who were adherent to the diet include

more frequent self-monitoring, receiving more feedback on self-monitoring records, and having

a greater variety of foods available to incorporate within the diet (82). Dietary adherence in

renal disease can be measured using subjective assessment, such as diet records, and objective

techniques, such as serum phosphorus levels (81).

Among strategies to improve dietary adherence mentioned by Burrowes & Cockram

(2003), the PPS was intended to promote self-monitoring which engages patients more actively

and to provide opportunity for positive reinforcement from the health care provider when the

records were analyzed together. Self-efficacy was encouraged as the patients were asked to

modify his or her eating behaviour while considering the total point goal, and were able to

associate their compliance to their serum phosphorus levels during their appointments with the

RD (81) . As well, setting a target goal of total phosphorus points to consume would give

patients something attainable to strive towards.

35

2.5.6 Innovations in the area of phosphorus control

Serum phosphorus control is often challenging, and this led Kuhlmann (2006) to develop

a phosphate education program (PEP) that enables patients to self-adjust the dose of phosphate

binder depending on the phosphorus content of the meal they are planning to consume. One

phosphorus unit (PU) is allotted per 100mg of phosphorus and Kuhlmann assigns PU values to

food groups instead of food components, to enable patients to be able to “eye-estimate” the meal

PU content (83). When the patient is able to estimate the phosphorus content of foods, they can

then self-adjust their binder dose according to a binder to PU ratio that has been prescribed by

the physician (83). Another potential positive aspect of this program is to ensure the patient is

only consuming the quantity of binders necessary, and not taking in excess calcium due to the

increased risk of hypercalcemia that occurs with an excessive intake of calcium (83) . No

studies demonstrating the effectiveness of the PEP have been published as of yet. The

development of the PEP program is based upon similar rationale as the PPS tool, and provides

evidence for the need of innovative phosphorus education tools for patients.

36

3.0 Rationale, Hypothesis, and Objectives

The risk of disease progression and complications such as metastatic calcification,

cardiovascular complications and the increased risk of morbidity and mortality which result

from hyperphosphatemia precipitate the need for improved phosphorus control in patients with

chronic kidney disease. Hyperphosphatemia occurs as a result of impaired renal phosphate

excretion, where there is a significant difference between the rates at which phosphate enters the

circulation and is excreted by the kidneys. The National Kidney Foundation-Kidney Disease

Outcomes Quality Initiative (KDOQI) and the Canadian Society of Nephrology recommend

patients with hyperphosphatemia restrict their dietary intake of phosphorus to between 800 and

1000mg per day and that patients with persistent hyperphosphatemia take phosphate binder

medication in combination with dietary restriction (43,44).

Adherence to a phosphorus restriction is often challenging for renal patients, in that there

are many food sources of phosphorus, phosphorus containing additives are frequently added to

foods, the patients often have other dietary guidelines to follow, including sodium, potassium

and/or fluid restrictions (18,25), and the patients often have numerous co-morbidities, and social,

familial and psychological issues that make them ill-disposed to follow dietary restrictions.

Innovative means for providing dietary phosphorus education, and the provision of more

frequent dietary instruction, have been demonstrated to improve management of

hyperphosphatemia (18,24,74,75).

The usual dietary education provided by renal dietitians to patients with

hyperphosphatemia includes a standard one page handout. The handout typically lists food items

that are high in phosphorus to avoid and substitution food items low in phosphorus to choose

more often. This tool along, with the limited time that patients are given with the dietitian,

37

may not provide the patients with enough knowledge and understanding of the diet to

successfully achieve adequate phosphorus control.

The Phosphorus Point System tool© (PPS) was developed at St. Michael’s Hospital and

is based on a system that allocates points for the amount of phosphorus in foods; it was designed

to allow for greater dietary flexibility, or an “all foods fit” philosophy. Patients are prescribed a

daily point total to strive towards (32 - 40 points or 800-1000 mg phosphorus), as well as the

tool which includes over 1,347 foods from the Canadian Nutrient File that are listed in

alphabetical order within food groups and given descriptive and common food measures. Points

are allocated based on the phosphorus content in the foods; 0.5 points for 12.5 milligrams

phosphorus or 1 point for 25 milligrams. Additionally, high potassium foods are highlighted

within the tool. Patients track their daily points, and along with more intensive support and

follow-up from the dietitian, are expected to have better knowledge, understanding and

motivation, and be better equipped to adhere to their diet.

The Phosphorus Point System© Tool was assessed through a focus group consisting of

peritoneal dialysis (PD) patients who were asked to evaluate the tool. The patients felt the tool

was a comprehensive educational tool that could be useful in increasing dietary flexibility. The

PPS was thereafter evaluated in a before-and-after study within a group of 10 peritoneal dialysis

patients, and the tool was found to significantly reduce serum phosphorus and calcium

phosphate product after one month of use. The tool has yet to be evaluated via a randomized

controlled trial, or within the pre-dialysis population. It was speculated that we would find same

effect of the PPS within the pre-dialysis population. Studies involving dietary phosphorus

interventions have yet to be completed within the pre-dialysis CKD population. It was also

thought that it would be helpful to initiate more intensive education in the earlier stages of

kidney disease, thus supporting the intention to investigate the effect of this tool within this

population.

38

Thus, the rationale for the current study is that, in the pre-dialysis population: 1) dietary

phosphorus restriction is prescribed to hyperphosphatemic pre-dialysis patients in order to

reduce serum phosphorus levels and possibly reduce health-related complications, 2) studies

have shown that more intensive follow-up and approaches in dialysis patients can lead to

improvement in dietary adherence and satisfaction 3) studies involving intensive, innovative

patient education interventions have not been previously conducted in the pre-dialysis patient

population to our knowledge, and the evaluation of the PPS within this population has also not

been completed.

Our primary objective is to determine the effect of intensive dietary phosphorus teaching using

the PPS versus standard teaching with the Choose/Avoid list over a 12 week period on:

! Serum phosphorus levels

!

Secondary objectives include determining the effects of the PPS versus standard teaching over

a 12 week period on:

! Dietary intake and satisfaction

! Knowledge of dietary phosphorus content in patients with pre-dialysis chronic kidney

disease

Our primary hypothesis is that in patients educated by the PPS:

! Serum phosphorus levels will be lower than those of patients receiving the standard

education.

39

Secondary hypotheses include:

! Dietary intake of phosphorus will be reduced and satisfaction will be improved by

providing patients with the more intensive and tangible educational principles of the PPS

tool

! Knowledge-level of phosphorus-containing foods and the importance of compliance to

phosphorus restriction will be greater in patients using the PPS versus the standard

education.

40

4.0 Methods 4.1 Study design

The study was a randomized controlled clinical trial that involved pre-dialysis kidney

disease patients at St. Michael’s Hospital and Sunnybrook Hospital in Toronto. Participants

were followed for 12 weeks, and measures were collected at 3 time points: week 0, week 6 and

week 12. Dietary education using the innovative Phosphorus Point System Tool© was provided

to the intervention group; dietary compliance was measured via serum phosphorus levels and

dietary recall, and dietary satisfaction and phosphorus knowledge-level were measured via tools.

Ethics approval was obtained from the Research Ethics Boards at both St. Michael’s Hospital

and Sunnybrook Hospital. Informed consent was obtained from patients in-person before the

onset of the study (Appendix, Forms 1 & 2).

4.2 Eligibility and recruitment

4.2.1. Eligibility

Patients who were eligible were adults greater than 18 years of age. Patients had to be

attending a pre-dialysis outpatient clinic at St. Michael’s Hospital or Sunnybrook Hospital, or

attending a nephrologists’ private clinic at one of these site, as these were the locations from

which participant recruitment was conducted. Prevalent clinic patients were required to have a

6-month mean serum phosphorus level greater than 1.35 mmol/L, to demonstrate persistent

hyperphosphatemia. Patients new to the clinics were required to have their most recent serum

phosphorus level greater than 1.35 mmol/L.

Patients were excluded if they were undergoing dialysis during the study period, as this

would indicate the patients were in end-stage renal disease, and could no longer remain

classified as being pre-dialysis patients. Patients with malignancy were excluded in an attempt

to avoid confounding variables. Those who were unable to read or write in English were

41

excluded, as the tool required these abilities for its use. If the patient was also deemed unable to

use the tool based on the experience of the health care team, the patient was excluded.

4.2.2 Recruitment method

All subjects receiving pre-dialysis renal care at St. Michael’s Hospital and Sunnybrook

during the recruitment period were identified. Patients were initially screened for their most

recent serum phosphorus levels, and those with levels greater then 1.35 mmol/L were identified.

Further investigation into whether they met the inclusion and exclusion criteria was completed

using information from the medical charts and electronic patient charting databases (Appendix,

Forms 3 & 4). Eligible patients were initially contacted by the clinic dietitian, the clinic nurse

practitioner, or the clinic nephrologists, and asked whether the investigator, who was also a

Registered Dietitian, could contact them to provide further information about the study and

inquire about their willingness to participate. If the patient agreed, the investigator then outlined

the study to the patient over the telephone or in-person, described the nature of the study and

voluntary participation was explained to ensure patients were aware that declining participation

would not affect their medical care at St. Michael’s Hospital or Sunnybrook Hospital.

4.3 Study procedures Pre-dialysis patients who met the eligibility criteria, and were willing to participate, were

either mailed or given in-person, a package containing a blood work requisition, a Food Portion

Visual guide and measuring cups and spoons. Patients then were either called on the telephone

or asked in-person for the first of the repeated 5-step multiple-pass 24-hour recalls (Appendix,

Form 5) and to book the first study visit. Patients were randomized to either the control

Standard Education (SE) group or the intervention Phosphorus Point System© Tool (PPS) group

at the onset of their first study visit. Concealed randomization was completed with the

assistance of a Biostatistician who completed random numbers generation and concealed group

42

assignments in individually labeled, sealed security-lined envelopes. Group assignments were

blinded to the investigator up until the beginning of the participant’s first study visit.

At baseline, all participants had serum measures collected (detailed in section 4.4),

completed repeated 5-step multiple-pass 24-hour dietary recalls and answered questions about

their intake of processed foods (Appendix, Form 6) (detailed in 4.5), completed a dietary

satisfaction questionnaire (Appendix, Form 7) and a phosphorus knowledge test (Appendix,

Form 8) (detailed in 4.6 & 4.7, respectively). Thereafter, dietary phosphorus education was

provided.

At week 6 and 12, the measures were repeated again with both groups; these included

serum measures, repeated 24-hour dietary recalls and processed food intake data collection,

dietary satisfaction questionnaire, and the phosphorus knowledge test. At week 6, the logbook

of phosphate points consumed by the participant was reviewed by the investigator with the

participant. Feedback was given based on accuracy of point assignment to food items and

participants were encouraged to remain within the 32-40 point total per day. Participants were

reimbursed in the quantity of $20 at each study visit for transportation costs. One of each set of

repeated dietary recalls were completed over the telephone at each time interval to minimize

patient burden by reducing the number of study visits. Patients randomized to the control group,

who desired to learn the PPS method, were provided with this education upon completion of the

study. Details of the study timeline are provided in Table 4.0 and Figure 4.0.

4.3.1 Standard Education

The control group received the standard Choose/Avoid (C/A) phosphorus education at

baseline from the investigator, who was also a Registered Dietitian. This dietary education was

provided via a one-page double-sided handout provided to patients which lists foods high in

phosphorus to avoid, and low phosphorus foods to consume more frequently (Appendix, Form

9).

43

Figure 4.0 – Twelve week Study Design

44

Table 4.0 – Schedule of Key Study Measurements

Timeline Week

0 Week

1 Week

2 Week

3 Week

4 Week

5 Week

6 Week

11 Week

12 Demographics X 24-hour dietary recall X X X X X X Phosphorus questionnaire X X X Satisfaction questionnaire X X X Processed food intake questionnaire X X X Phosphorus education X Follow-up phone call X X X X Height/Weight X X X Routine Blood Work Phosphorus X X X Calcium X X X Albumin X X X Alkaline Phosphatase X X X Parathyroid Hormone X X

45

4.3.2 Intervention PPS Education

The intervention group was also educated by the investigator to follow a phosphorus

restricted diet using the Phosphorus Point System© Tool (PPS) (Appendix, Form 10). Teaching

was performed via the introduction of the booklet to the participant, and the instruction to

consume no more than 40 phosphorus points per day, which is equal to 1000 mg of phosphorus.

Participants learned to assign points to food by practicing on the food they had previously

consumed that day, with the assistance of the dietitian. Discussion surrounding meal planning

and ensuring adequate protein consumption by allocating daily points to protein-rich foods as a

priority were discussed. Education also focused on explaining phosphorus metabolism, the risks

of hyperphosphatemia, and the use of phosphate binders to the participants. Participants were

given a copy of the PPS tool, tally sheets to track the points consumed daily (Appendix, Form

11), and were instructed to attempt to maintain routine phosphate binder consumption.

Participants in the intervention group also received weekly follow-up telephone calls for six

weeks to identify and address any questions or concerns about the tool and to assist with point

determination of foods not listed within the booklet (Appendix, Form 12). At the six-week

study visit, participants were given the option of continuing to track daily phosphorus points or

to use the tool as a reference with the intention that learning had occurred through 6 weeks of

recording intake, and participants would have become skilled in assigning points to their typical

eating pattern. At week 6 and 12, participant feedback on the tool was collected.

All study participants were taught about phosphorus additives via a handout which

outlined the names of these additives, as well as the foods in which they are most frequently

found (Appendix, Form 13). This handout was provided to all patients, as this was an essential

component to be included in routine care. Participants in the intervention PPS group received

more intensive phosphorus additive education through demonstration with food package labels.

46

4.3.3 Data collection

Comparative characteristics collected at baseline included: age, gender, cause of renal

disease, past medical history, medication regimen, body weight, height, and the existence of

previous dietary phosphorus instruction. Body mass index was calculated.

4.4 Serum measures

The following serum values were monitored: serum phosphate, serum calcium, serum

PTH, serum albumin, serum creatinine and serum alkaline phosphatase (ALP). Calcium

phosphate product was calculated by using the product of serum phosphate and corrected serum

calcium. Serum values were collected at baseline, week 6 and week 12. Serum PTH was only

collected at baseline and week 12, as a clinically meaningful change in this value would likely

not be evident after 6 weeks. Serum measures were collected to determine whether the

participants complied with the education and if this could be reflected within serum values, and

this satisfies level three of the four levels of evaluating the effectiveness of education.

Participants were permitted to have blood taken either at the hospital they attend or at an

outside lab, whichever was of greatest convenience for them. The majority of patients had

blood drawn at SMH, however there were some that did not.

Phosphorus, calcium, albumin, ALP and creatinine analyses were performed on

Beckman Coulter DxC/LX20 SYNCHRON Clinical Systems, and PTH assay was performed on

the Roche Elecsys 2010 analyzer in the patient phlebotomy laboratories at St. Michael’s

Hospital.

The serum phosphorus concentration is determined using phosphorus (PHS) reagent with

a timed endpoint method. The reaction involves inorganic phosphorus reacting with ammonium

molybdate within an acidic solution to form a coloured phosphomolybdate complex. The

SYNCHRON LX® System (Beckman Coulter) then proportions one part of sample to 67 parts

47

reagent in a cuvette. The SYNCHRON monitors the change in absorbance at 340 nanometers

(nm). The change in absorbance in directly proportional to the concentration of inorganic

phosphorus within the sample and thus the system calculates and expresses the phosphorus

concentration.

Analyses performed by a clinical chemist at SMH found that the precision of the

measurement of serum phosphorus in the Core Lab has a coefficient of variation of 3%. The

chemist then sent the same 20 serum samples to four other laboratories, using five different

machines for analysis throughout the city, as not all of the study patients were having their study

blood work drawn at the lab at SMH, and the mean CV was found to be 3%. It should also be

noted that the biological variation of phosphorus has a coefficient of variation of 0.10.

Calcium is measured by indirect potentiometry utilizing a calcium ion selective

electrode. High molar strength buffer is used to establish a constant activity coefficient for

calcium ions. Total calcium is able to be calculated from free calcium when the molar ratio

between free and total calcium concentrations is constant; which is achieved by a buffering

solution containing strong calcium complexing agents. One part of sample volume (62 uL) is

mixed with 21 parts buffered solution. When the electrode contacts the sample buffer mixture,

the calcium ions react with the ionophore resulting in changes in the electrode potential. These

changes in potential are referenced to the sodium reference electrode. This reference potential

then follows the Nernst equation and allows the calculation of calcium concentration. To

improve accuracy, the reference reagent containing calcium ions is introduced into the flow cell

following the sample cycle and the same reaction scheme takes place again. The calculation of

calcium involves the differential potential between sample and reference reagent cycles.

The SYNCHRON LX System is used to measure albumin, ALP and creatinine.

Bromcresol Purple (BCP) reagent is used to determine the concentration of albumin using a

bichromatic digital endpoint method. The reagent and albumin from the sample combine to

48

form a bromcresol purple albumin complex. The change in absorbance, which is monitored at

600 nanometers, is directly proportional to the concentration of albumin in the sample. ALP

activity is measure by a kinetic rate method using AMP buffer. ALP catalyzes the hydrolysis of

the colourless organic phosphate ester substrate, p-nitrophenylphosphate, to a yellow coloured

product, p-nitrophenol, and phosphate. Creatinine concentration is determined using the

SYNCHRON LX system via the Jaffe rate method.

PTH is measured via a sandwich test principle using the Elecsys assay from Roche on

the 2010 analyzer. This principle involves a biotinylated monoclonal antibody which reacts

with the N-terminal fragment (1-37) and a monoclonal antibody labeled with a ruthenium

complex reacts with the C-terminal fragment (38-84). The antibodies in this assay are reactive

with the epitopes in the amino acids regions 26-32 and 27-42.

4.5 Estimated dietary intake

To evaluate the dietary intake of the participants, and to estimate the amount of

phosphorus being consumed, repeated 24-hour recalls were performed following the United

States Department of Agriculture (USDA) 5-pass multiple recall method (84,85). Mean 2-day

24-hour recall intake data was used to estimate dietary intake of the patients at each of the three

study time points.

24-hour recalls are considered to be the method of choice for assessing dietary intakes of

groups (86). The 5-pass recall method was developed in 2002, and is currently the preferred

method for collecting intake information used in national surveys in the United States and

Canada (87). This method consists of five steps: the quick list which allows respondents to list

foods consumed in past 24 hours in any desired order, the forgotten foods list which has

respondents answer questions about 9 food categories for additional foods, the time and

occasion of foods consumed are recalled, the detail cycle which asks respondents to provide

49

descriptions and amounts of each of the foods reported and the final probe which asks for any

other items that may have been consumed during the 24-hour time period (84). The 5-step

multiple pass 24-hour dietary recall method was adapted for use in the Canadian Community

Health Survey, Cycle 2.2 in 2004 (86). The preliminary testing group found that the questions

about where the food item or beverage was obtained and where the food item was consumed to

be too repetitive when asked along with the question about where the meal or snack was

prepared, and thus these two questions were not included (86) . This was also done in the

current study.

Numerous studies have been involved in determining the effectiveness and accuracy of

the 5-step multiple pass method, and have found this to be a valid and reliable method for

determining dietary intake (84,85,88-90).

In the current study the 5-step 24-hour recall method was completed with participants on

two separate occasions, once in person and once over the telephone, by a trained interviewer at

baseline, week 6 and week 12. A study comparing information collected by 24-hour recalls

using a three-step multiple pass method over the telephone to in-person recall information

collected in the Continuing Survey of Food Intakes by Individuals (CSFII), found that collecting

dietary intake information over the telephone is a practical and feasible method; however, the

use of 2–dimensional visuals to assist with portion size determination may have improved recall

accuracy (91), therefore supporting the use of a food portion visual guide within the current

study.

Participants were also asked about their phosphate binder regimen on the day of the

dietary recall, and thus an effort was made to determine whether the participants were adherent

to their binder regimen.

50

Dietary recalls were analyzed via ESHA Food Processor Software SQL Edition, Version

10.2 using the Canadian Nutrient File 2007b, and the dietary intake of phosphorus is therefore

based upon the content of phosphorus as indicated in the database.

Participants also answered questions about the frequency of their processed food dietary

intake at each of the three time points. Specifically, they were asked to quantify the frequency

and serving size of their consumption of fast food, deli meats, processed cheeses, boxed or

frozen meat products, canned fish, instant pudding, muffins, cake, cookies and cola (Appendix,

Form 6).

By assessing dietary intake and determining whether the participants incorporated their

learning into a behavioral change to their dietary intake, we attempted to satisfy level three of

the four levels of evaluating the effectiveness of education.

4.6 Dietary satisfaction measurement

Preliminary studies conducted with the PPS tool measured dietary satisfaction using a

modified questionnaire adapted from the validated questionnaire developed for the Modification

of Diet in Renal Disease Study (MDRD); this tool was also used in the current study to assess

dietary satisfaction (Appendix, Form 7). The concepts covered within this questionnaire

included thoughts on food choices such as satisfaction with intake, perceived challenges and

barriers, and food consumption during social events. This questionnaire was administered at

week 0, week 6 and week 12 to identify if participants’ dietary satisfaction changed over the

course of the study period. The assessment of dietary satisfaction aligns itself with level one of

evaluating the effectiveness of education, as this concept is related to the perception and opinion

of data.

51

4.7 Renal disease concept comprehension measurement

Several studies have evaluated the effectiveness of providing additional diet education to

patients with renal disease in improving knowledge about dietary phosphorus management

(18,34). The researchers used multiple choice questionnaires that addressed areas including

sources of phosphorus, consequences and causes of high phosphorus, and phosphate binders

(18,34). The questionnaire published by Ford et al (2004) was used to assess phosphorus

knowledge in the current study (Appendix, Form 8). Once again, this questionnaire was

administered at baseline, week 6 and week 12 to determine if phosphorus knowledge changed

over the course of the study period. The assessment of knowledge gained during the study

corresponds to the second level of evaluating the effectiveness of education which pertains to

knowledge, skills and attitudes.

4.8 Statistical analysis and sample size estimation

The target sample size for the study was 34 participants; 17 per group. This sample size

is based on calculation using power of 80%, standard deviation of 0.35 mmol/L, a meaningful

difference in serum phosphorus of 0.35 mmol/L, with a two-sided alpha of 5%, and was

determined using the assistance of a statistician from St. Michael’s Hospital (SMH) Li Ka Shing

Knowledge Institute.

These numbers are based upon significant studies of a similar nature. The PPS study

involving 10 peritoneal dialysis participants resulted in a difference in serum phosphorus of 0.20

mmol/L (p=0.019). The RCT study by Ford et al. (2004) used a sample size of 63 patients,

serum phosphorus of experimental group decreased from 2.21±0.17 to 1.70±0.28 mmol/L

(difference of 0.48) (p=0.0001). The RCT study by DeBrito Ashurst et al. (2004) with a sample

size of 58 total patients found the mean phosphorus level in the experimental group decreased

from 1.96 to 1.60 (difference of 0.36), p=0.02. Thus the mean statistically significant difference

52

in serum phosphorus levels in the literature was 0.35 mmol/L. Additionally, Block et al (2006)

found that an increase in serum phosphorus levels of 0.32 mmol/L increases the risk of mortality

by 6% in hemodialysis patients. Thus a significant difference of 0.35 mmol/L was selected for

the sample size calculation.

To determine the standard deviation (SD) of 0.35 mmol/L, the SDs from the preliminary

study with the PPS in the peritoneal dialysis population was used. At baseline the SD of

phosphorus levels in this group was 0.40, and at study conclusion was 0.34. As well, the SD of

hyperphosphatemic CKD patients in the clinic at SMH before the study began was 0.3390.

Thus the mean of 0.35 was chosen by the statistician for the determination of the sample size.

Analysis was completed using Statistical Package for the Social Sciences (SPSS)

Version 17.0 for Windows (Statistical Package for the Social Sciences, SPSS Inc., Chicago,

Illinois). Means and standard deviations were used to describe data. Results of noncontinuous

variables were expressed as numbers and percentage. Paired t-tests were used to compare the

laboratory results, dietary recall data, satisfaction survey results and knowledge test results from

baseline to study conclusion in both groups, and independent samples t-test were used to look at

differences between the intervention and control group. Continuous variables, which were not

normally distributed, were compared using the Mann Whitney U test for intergroup tests, and

the Wilcoxon Signed Ranked Test for intragroup tests. Linear regression was used to determine

intergroup differences at week 6 and week 12 adjusted for differences in the measures at

baseline. The chi-square test was used to examine associations between categorical

noncontinuous variables (eg. education level, income, and CKD etiology). Dietary intake

analyses of dietary protein intake in grams with respect to kilograms body weight in the patients,

was completed with adjusted body weight, as is typically done in clinical practice. If BMI was

between 27 and 30, body weight was adjusted for a BMI of 25. If the BMI was greater than

30.1, body weight was adjusted for a BMI of 27. Adjusted body weight is used to determine

53

protein requirements to avoid overfeeding the overweight or obese patient and to avoid over

consumption of protein, as CKD protein requirements are 0.80g/kg/day (92). It is potentially

hazardous to ignore the effects of body size on dietary requirements in those who are

overweight, as high protein intake can increase albuminuria and could accelerate the loss of

kidney function (93). Differences of analyses were considered significant when p < 0.05.

54

5.0 Results

5.1 Participant Recruitment

Over the period of one year, 160 (36%) patients with documented hyperphosphatemia,

out of a total of 448 patients who were screened at St. Michael’s Hospital, were considered for

possible inclusion in the study. The remaining 228 screened patients were not considered for

inclusion in the study due to insufficiently high levels of serum phosphorus. Twenty-four

patients (9%) at Sunnybrook Hospital with hyperphosphatemia, out of 264 screened, were

considered for inclusion; those not considered also had insufficiently high levels of serum

phosphorus. In total, of these 184 patients there were 103 who were not eligible, for reasons

such as the mean six-month serum phosphorus level was not greater than 1.35 mmol/L (n=51),

the patients were deemed unable to use the tool due to cognition levels or instability of the

patients (n=25), insufficient English literacy skills (n=13), dialysis initiation was imminent

(n=8), they resided in a nursing home wherein a set meal is provided (n=3), malignancy (n=2),

or the patient was deemed palliative (n=1) (Figure 5.0). 50 people declined to participate, and

24 people were enrolled. Although a large number of patients were ineligible for inclusion in

the study due to insufficiently high levels of serum phosphorus, this is secondary to a need to

include study participants with persistent hyperphosphatemia, to enable us to show a change in

serum phosphorus levels. Patients in a clinical setting who are hyperphosphatemic on one

occasion, receive dietary education to follow a low phosphorus diet and asked to adhere to this

diet even when normal phosphorus levels are seen upon subsequent measures. Patient

screening, recruitment and data collection at SMH and at Sunnybrook Hospital commenced

upon receipt of ethics approval at each site.

Eleven patients were randomized to the Phosphorus Point System Tool (PPS) group, and

13 were randomized to receive Standard Education (SE). At week 6, 1 person in the PPS group

55

94 Ineligible patients 51 Six-month mean phosphorus not elevated 20 Deemed unable to use tool (cognition level/instability) 9 Language barrier 8 Dialysis imminent 3 Reside in nursing home 2 Cancer 1 Palliative

448 screened pre-dialysis CKD patients at St. Michael’s Hospital over 1 year period

160 patients with hyperphosphatemia in past 6 months of their chart review

66 eligible SMH patients

44 Declined 22 Enrolled

264 screened pre-dialysis CKD patients at Sunnybrook Hospital over 2 month period

24 patients with hyperphosphatemia in past 6 months of their chart review

9 Ineligible patients 5 Deemed unable to use tool (cognition level/instability) 4 Language barrier

8 eligible Sunnybrook patients

6 Declined2 Enrolled

24 Enrolled

Randomization

11 Phosphorus Point System Education 13 Standard Education

7 completed week 12 of trial

9* completed week 12 of trial

* pt at wk 6 who failed to attend, returned at wk 12

10 completed week 6 of trial 11 completed week 6 of trial

Withdrawn due to transplant n=1

Withdrawn due to dialysis start n=2 Failed to attend appointment n=1

Withdrawn due to dialysis start n=1 Failed to attend appointment n=1

Withdrawn due to dialysis start n=1 Withdrawn due to transplant n=1 Blood work at wk 12 incomplete n=1

Figure 5.0 - Profile of Subject Recruitment and Study Completion

56

was withdrawn as they received a kidney transplant, and 2 people in the SE group were

withdrawn (1 started dialysis and 1 failed to attend the study visit). At week 12, 3 people in the

PPS group were withdrawn (2 started dialysis, 1 failed to attend the study visit), and 2 were

withdrawn from the SE group (1 received transplant, 1 started dialysis). One participant in the

SE group did not complete blood work at week 12 but completed the other measures, and the

participant who was unable to attend the visit at week 6 did attend at week 12. Thus in total, 7

participants in the PPS group completed the 12-week study, and 9 participants in the SE group

completed the 12-week study.

5.2 Characteristics of Participants

Characteristics of participants at baseline are summarized in Table 5.0. There was a

significantly higher number of males in the control group, compared to the PPS group at

baseline, despite using concealed randomization techniques. Forty-six percent of total

participants were classified as obese (BMI >30), and 33% of participants were classified as

overweight (BMI 25.0 – 29.9). No significant differences were seen between groups in terms of

age, ethnicity, etiology of CKD, GFR, stage of CKD, prescribed phosphate binders, prescribed

vitamin D medication, months receiving CKD dietary education, education level, income, and

nutritional parameters. The majority of participants were prescribed a phosphate binder.

5.3 Serum Phosphorus and Other Biochemical Measures

Within-group and between-group analyses of serum phosphorus and biochemical

measures were completed at week 6 and also at week 12, table 5.1 & 5.2. There were no

significant differences at baseline between groups, other than a significant difference in serum

calcium; however both mean values were within serum target level.

The Phosphorus Point System Tool reduced 12 week serum phosphorus levels by 0.16

mmol/L (95% CI 0.37 to -0.05, p=0.130) when controlling for serum phosphorus at baseline.

57

Table 5.0 Clinical and Demographic Characteristics of Participants

Characteristics PPS Group SE Group p value n = 11 n = 13 Age, mean (SD), y 56 (10) 53 (13) 0.590 Sex, n (%) Male 3 (27%) 10 (77%) 0.015a Female 8 (73%) 3 (23%) Ethnicity, n (%) Aboriginal 0 (0%) 1 (8%) 0.380 Africans/Black 2 (19%) 1 (8%) East Asian 1 (9%) 1 (8%) European/White 8 (73%) 7 (54%) Latin American 0 (0%) 1 (8%) South Asian 0 (0%) 2 (15%) Etiology of Chronic Kidney Disease, n (%) Diabetic Nephropathy 5 (45%) 6 (46%) 0.501 Glomerulonephropathy 0 (0%) 1 (8%) Ischemic/renovascular Disease 2 (18%) 3 (23%) Autoimmune Disease 2 (18%) 0 (0%) Other 2 (18%) 3 (23%) GFR (mL/min/1.73 m2)* 12 (8-66) 14 (5-32) 0.642 Stages of Chronic Kidney Disease, n (%) Stage 3 0 (0%) 1 (7.7%) 0.503 Stage 4 3 (27.3%) 5 (38.5%) Stage 5 7 (63.6%) 7 (53.8%) Prescribed Phosphate Binder, n (%) No binder 3 (27%) 4 (31%) 0.539 Calcium carbonate 7 (64%) 9 (69%) Aluminum hydroxide 30 mg/d 1 (9%) 0 (0%) Months receiving CKD dietary education, n (%) No previous diet education 1 (9%) 1 (8%) 0.530 < 6 months 3 (27%) 2 (15%) 6-24 months 2 (18%) 5 (38%) ! 25 months 5 (45%) 5 (38%) Education level, n (%) Elementary school 1 (9%) 0 (0%) 0.459 Some high school 2 (18%) 0 (0%) High school diploma 2 (18%) 4 (31%) Some college/university 3 (27%) 4 (31%) College/University degree 3 (27%) 5 (45%) Household Income, n (%) Greater than $80,000 2 (18%) 2 (15%) 0.778 $40,000 - less than $80,000 3 (27%) 3 (23%) $20,000 - less than $40,000 1 (9%) 2 (15%) Less than $20,000 2 (18%) 4 (31%) No income 1 (9%) 0 (0%) Unknown 2 (18%) 2 (2%) Nutrition, mean (SD) Weight (kg) 87.7 (26) 85.4 (15) 0.800 Height (cm) 163 (7) 170 (8.5) 0.060 BMI (kg/m2) 33.6 (10.5) 30.3 (4.9) 0.380 Values are means (SD) or n (%), analyzed by Independent samples t-tests or Pearsons Chi-square test * GFR values are median (min-max), analyzed by Mann Whitney U test. a Significant when p<0.05

Table 5.1 Effect of Standard Education (SE) and Phosphorus Point System Tool (PPS) on Biochemical Variables in Participants at Week 6 SE PPS n=11 n=10

Baseline Week 6 Intragroup

p-value Baseline Week 6 Intragroup

p-value

Intergroup p-value Baseline

Adjusted Intergroup Difference (95% CI)

Week 6

Adjusted Intergroup

p-value Week 6

Serum Phosphate (mmol/L) 1.47 (0.28) 1.56 (0.30) 0.448 1.50 (0.22) 1.54 (0.30) 0.658 0.766 -0.03 (0.30 to -0.24) 0.811 Corrected calcium (mmol/L) 2.31 (0.16) 2.29 (0.19) 0.453 2.43 (0.11) 2.40 (0.12) 0.106 0.025a -0.02 (0.09 to -0.05) 0.587 Calcium phosphate product (mmol/L) 3.40 (0.69) 3.42 (0.70) 0.929 3.66 (0.56) 3.70 (0.76) 0.823 0.514 0.20 (0.88 to -0.48) 0.539 Albumin 35.55 (8.9) 35.55 (9.1) 1.000 36.34 (4.3) 38.12 (5.0) 0.113 0.639 1.91 (4.71 to -1.07) 0.202 iPTH (pmol/L)** Alkaline phosphatase 100 (78) 105 (66) 0.706 93 (36) 87 (23) 0.460 0.521 -12.32 (39.5 to -14.8) 0.352

Creatinine 404 (162) 433 (208) 0.146 365 (175) 376 (192) 0.610 0.599 -12.51 (70.10 to -

45.09) 0.654 GFR 14 (5-32) 15 (5-31) 0.952 13 (8-66) 12.5 (6-51) 0.719 0.642 -0.80 (3.38 to -1.79) 0.527 Values are mean (SD) and analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusting for differences at baseline GFR values are medians (min-max) and analyzed by non-parametric Wilcoxon, Mann Whitney U ** no PTH measurement at wk 6

a - statistically significant at p<0.05

58

Table 5.2 Effect of Standard Education (SE) and Phosphorus Point System Tool (PPS) on Biochemical Variables in Participants at Week 12 SE PPS n=9 n=7

Baseline Week 12 Intragroup

p-value Baseline Week 12 Intragroup

p-value

Intergroup p-value Baseline

Adjusted Intergroup Difference (95% CI)

Week 12

Adjusted Intergroup

p-value Week 12

Serum Phosphate (mmol/L) 1.43 (0.31)**

1.57 (0.29)** 0.117 1.42 (0.13) 1.40 (0.17) 0.821 0.766 -0.16 (0.37 to -0.05) 0.130

Corrected calcium (mmol/L) 2.31 (0.16) 2.31 (0.17) 0.860 2.43 (0.14) 2.40 (0.13) 0.111 0.025a -0.01 (0.10 to -0.80) 0.744 Calcium phosphate product (mmol/L) 3.35 (0.73) 3.61 (0.64) 0.233 3.46 (0.39) 3.36 (0.42) 0.617 0.514 -0.30 (0.82 to -0.22) 0.236 Albumin 35.11 (9.8) 34.33 (9.0) 0.469 36.06 (4) 37.59 (4) 0.197 0.639 2.38 (5.59 to -0.73) 0.121

iPTH (pmol/L) 18.8 (5.2-

50.5)** 19.8 (2.4-

52)** 0.889 8.10 (3.8-

131.6)* 11.5 (4.9-

144.7)* 0.249 0.278 3.42 (11.39 to -4.55) 0.365 Alkaline phosphatase 105 (86) 93 (49) 0.862 95 (36) 93 (26) 0.862 0.521 5.24 (30.10 to -19.62) 0.657 Creatinine 396 (180) 441 (252) 0.206 354 (202) 351 (200) 0.791 0.599 -41.77(122.54 to -39.0) 0.284 GFR 16 (5-32) 16 (4-29) 0.223 12 (10-66) 14 (10-48) 0.832 0.642 0.36 (3.28 to -2.55) 0.793 Values are mean (SD) and analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusting for differences at baseline GFR and PTH values are medians (min-max) and analyzed by non-parametric Wilcoxon, Mann Whitney U * - n=6 ** - n=8 a - statistically significant at p<0.05

59

60

Linear regression analyses were also completed while adjusting for differences in GFR at

baseline and these results did not differ from those where we only adjusted for differences in the

measure itself at baseline. Therefore we did not complete these adjustments, as we did not want

to over adjust our data which was based on a low sample size.

Other serum measures did not differ significantly between groups at week 6 or week

12. There were also no significant changes in serum phosphorus or other serum measures

within groups from baseline to week 6, or baseline to week 12,

As seen in figures 5.0 and 5.1, there is a significant negative correlation between serum

phosphorus levels and GFR, which is to be expected as when renal function declines, the ability

of the kidneys to excrete phosphate worsens thus resulting in increased phosphate retention (12).

With regards to the stages of CKD within which the participants were classified, there

were no significant differences between groups at the three time points.

Of the participants who completed the 12-week study, the proportion of participants with

serum phosphorus levels less than 1.50 mmol/L at baseline were 6 (75%) participants in the SE

group and 5 (71%) in the PPS group; these participants could be classified as having levels

below the KDOQI target for serum phosphorus. At week 12, 3 (38%) in the SE group and 5

(71%) in the PPS group had serum phosphorus levels less than 1.50 mmol/L. These differences

were not significant as measured by McNemar’s test.

5.4 Dietary Outcomes

5.4.1 Dietary and Phosphate Binder Intake

Within-group and between-group analyses of dietary intake were completed at week 6

and also at week 12; see Table 5.3 and 5.4. Dietary phosphorus intake was significantly lower

at week 6 in the PPS group compared to the control group. The phosphorus intake, expressed as

milligrams per gram of protein, in the SE group was significantly higher at week 6 compared to

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Figure 5.1 Relationship between Serum Phosphate concentration and Kidney Function as measured by Glomerular Filtration rate (GFR, mL/min/1.73 m2) in participants with Chronic Kidney Disease (n=24) at Baseline. (---- indicates cut-off point for hyperphosphatemia as determined by the Kidney Disease Outcomes Quality Initiative KDOQI)

Figure 5.2 Relationship between Serum Phosphate concentration and Kidney Function as measured by Glomerular Filtration rate (GFR, mL/min/1.73 m2) in participants with Chronic Kidney Disease (n= 15) at Week 12. (---- indicates cut-off point for hyperphosphatemia as determined by the Kidney Disease Outcomes Quality Initiative)

r = -0.404 p = 0.050

r = -0.564 p = 0.028

Table 5.3 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Estimated Mean 2-Day Dietary Intake of Phosphorus, and Selected Nutrients and Phosphate Binders in Participants at Week 6

SE PPS Baseline Week 6 Change Baseline Week 6 Change

Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Inter-group

p-value Baseline

Adjusted Intergroup

p-value Week 6

Mean 2-Day Dietary Intake

Parameters

n = 11 n = 11

p

n = 10 n = 10

p

p p Phosphorous (mg/day) 936 (271) 952 (231) 15 (348) 0.877 824 (376) 675 (276) -150 (255) 0.097 0.692 0.026a Phosphorous/ Protein (mg/g) 15.3 (2.9) 13.7 (2.6) -1.6 (2.1) 0.014a 12.9 (3.3) 14.2 (4.4) 1.3 (3.5) 0.277 0.130 0.083 Protein (g/day)

64 (25) 73 (24) 9 (20) 0.152 64 (27) 53 (34) -11 (27) 0.219 0.855 0.050a Protein/Adjusted Body Weight (g/kg) 0.88 (0.4) 0.97 (0.3) 0.09 (0.3) 0.329 0.95 (0.4) 0.76 (0.4) -0.2 (0.4) 0.166 0.538 0.087 Calcium (mg/day) 546 (254) 507 (226) 40 (258) 0.698 445 (187) 444 (171) -1.3 (210) 0.985 0.696 0.505 Potassium (mg/day) 2161 (645) 1925 (564) -236 (510) 0.122 1816 (656) 1301 (591) -515 (407) 0.003a 0.431 0.036a Sodium (mg/day) 1644 (703) 1941 (1075) 297 (1193) 0.387 2027 (1829) 1846 (822) -181 (1839) 0.762 0.292 0.741 Energy (Kcal/day) 1377 (400) 1450 (355) 73 (508) 0.616 1459 (651) 1167 (416) -292 (549) 0.127 0.501 0.063 Energy (Kcal/Kg/day) 16.5 (5.4) 17.1 (4.7) 0.6 (6.0) 0.756 16.6 (6.4) 13.8 (5.3) -2.8 (5.8) 0.163 0.614 0.124 Phosphate binder - Calcium carbonate (mg/day) 1675 (1007)* 1772 (1213) 97 (1812) 0.876

1713 (1119)** 1659 (1195) -54 (1468) 0.893 0.914 0.622

Weight (kg) 86.0 (13) 87.8 (13) 1.81 (2.4) 0.034a 88.7 (27.5) 87.2 (26.9) -1.48 (1.83) 0.031a 0.802 0.003a BMI 29.7 (4.7) 30.3 (4.7) 0.65 (0.99) 0.056a 34.5 (10.7) 33.9 (10.4) -0.57 (0.74) 0.051a 0.379 0.018a Values are mean (SD), analyzed by Paired samples t-tests, Independent samples t–tests, Linear regression adjusted for differences at baseline a statistically significant at p<0.05

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Table 5.4 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Estimated Mean 2-Day Dietary Intake of Phosphorus, and Selected Nutrients and Phosphate Binders in Participants at Week 12

SE PPS Baseline Week 12 Change Baseline Week 12 Change

Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Inter-group

p-value Baseline

Adjusted Intergroup

p-value Week 12

Mean 2-Day Dietary Intake

Parameters

n = 10 n = 10

p

n = 8 n = 8

p

p p Phosphorous (mg/day) 966 (298) 863 (251) -103 (235) 0.198 867 (348) 721 (302) -145 (259) 0.156 0.692 0.415 Phosphorous/ Protein (mg/g) 14.8 (2.7) 12.8 (4.6) -2.0 (3.4) 0.096 13.2 (2.2) 15.1 (1.8) 1.9 (2.2) 0.041a 0.130 0.026a Protein (g/day) 68 (27) 77 (237) 9 (32) 0.385 67 (29) 50 (25) -17 (23) 0.067 0.855 0.057 Protein/Adjusted Body Weight (g/kg) 0.93 (0.3) 1.03 (0.5) 0.10 (0.4) 0.493 1.01 (0.5) 0.75 (0.4) -0.25 (0.4) 0.115 0.538 0.120 Calcium (mg/day) 541 (270) 493 (202) -49 (172) 0.395 473 (197) 431 (173) -42 (227) 0.620 0.696 0.705 Potassium (mg/day) 2234 (623) 1971 (776) -263 (879) 0.369 1824 (686) 1337 (427) -487 (312) 0.003a 0.431 0.149 Sodium (mg/day) 1425 (560) 1433 (677) 7 (510) 0.964 2160 (2019) 2053 (1034) -108 (1928) 0.879 0.292 0.280 Energy (Kcal/day) 1354 (426) 1441 (373) 87 (367) 0.470 1486 (672) 1249 (349) -237 (529) 0.246 0.501 0.114 Energy (Kcal/Kg/day) 15.1 (4.7) 15.6 (4.6) 0.5 (3.4) 0.678 15.4 (6.2) 13.8 (5.7) -1.6 (5.0) 0.416 0.614 0.317 Phosphate binder - Calcium carbonate (mg/day) 1825 (979)* 2079 (531) 254 (625) 0.365

1835 (1195)** 1963 (972) 128 (499) 0.440 0.914 0.277

Weight (kg) 90.2 (12.9) 90.6 (12.9) 0.44 (2.4) 0.589 98.5 (27.0) 96.9 (25.8) -1.5 (2.7) 0.185 0.802 0.219 BMI 31.5 (4.8) 31.7 (5.1) 0.14 (0.88) 0.636 37.3 (10.3) 36.8 (9.7) -0.61 (1) 0.157 0.379 0.301 Values are mean (SD), analyzed by Paired samples t-tests, Independent samples t–tests, Linear regression adjusted for differences at baseline a - significant when p<0.05

63

64

baseline. Phosphorus intake, expressed as milligrams per gram of protein, recommendations for

patients with GFR<60 are 8-12 mg/g. Protein intake was significantly lower at week 6 in the

PPS group compared to the SE group. At week 12, the phosphorus intake, expressed as

milligrams per gram of protein, in the PPS group was significantly higher compared to baseline,

and also significantly higher at week 12 in the PPS group compared to SE. At week 12, the

difference in protein intake between the SE and PPS group was nearing significance, intake was

higher in the SE than PPS group.

Based upon mean 2-day intake within the SE group, 23%, 55% and 10% of participants

consumed more than 1000 mg phosphorus per day at baseline, week 6, and week 12,

respectively. Within the PPS group, 55%, 0%, and 25% of participants consumed more than

1000mg phosphorus per day at baseline, week 6, and week 12, respectively.

Potassium intake within the PPS group was significantly lower at week 6 compared to

baseline. Potassium intake was also significantly lower in the PPS group compared to the SE

group at week 6. At week 12, potassium intake was significant lower compared to baseline in

the PPS group.

Based upon mean 2-day dietary intake via repeated 24-hour recalls, there were no

significant differences with respect to energy intake. Weight and BMI significantly decreased in

the PPS group at week 6 compared to baseline. Alternatively, weight and BMI significantly

increased in the SE group at week 6 compared to baseline. Weight and BMI were significantly

different from PPS group versus SE group at week 6.

There were no significant differences in reported intake of calcium carbonate phosphate

binders. Nine participants in the SE group were taking binders, and 6 participants in the PPS

group. As well, participants who were not taking binders at the study onset continued with this

regimen; 4 participants in the SE group and 3 in the PPS group. Another participant in the PPS

65

group was assigned to take aluminum hydroxide as a phosphate binder, and was consistent in

taking this as prescribed.

5.4.2 Phosphorus Knowledge Scores

With regards to mean total phosphorus knowledge test scores, there were no significant

differences between or within groups at week 6 or week 12, as seen in Table 5.5 & 5.6.

Phosphorus knowledge test scores were also grouped based upon category. The four categories

include general phosphorus knowledge, knowledge of food content of phosphorus, knowledge

surrounding phosphate binders and knowledge of phosphorus metabolism. Knowledge of

phosphate binders and their role in CKD management was significantly higher in the PPS group

compared to SE at week 12. There were no other significant differences between or within

groups based upon these categories at week 6 or week 12. The improvement in both the total

knowledge score and the score on questions related to general phosphorus management in the

PPS group did not reach statistical significance.

5.4.3 Dietary Satisfaction Scores

The mean total dietary satisfaction score was significantly higher at week 12 compared

to baseline in the SE group. There were no significant changes with respect to the PPS

intervention in dietary satisfaction scores. There were no significant differences when

considering satisfaction with regards to the key concepts of satisfaction with food choices, or

social aspects of food, as indicated in Table 5.7 & 5.8.

5.4.4 Qualitative Satisfaction data

Comments and thoughts about the PPS tool were collected at week 6, week 12 and

during the weekly follow-up phone calls in the PPS group. These were noted and recorded

(Table 5.9).

Table 5.5 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Knowledge Test Scores of the Participants at Week 6 SE (n=11) PPS (n=10)

Topic Baseline score

Week 6 score Change p-value

Baseline score

Week 6 score Change p-value

Intergroup baseline p-value

Adjusted Intergroup

week 6 p-value

General (5 points) 2.4 (1.2) 2.8 (1.0) 0.4 (1.4) 0.296 2.4 (1.4) 2.7 (1.6) 0.3 (1.3) 0.496 0.584 0.797 Food content (6 points) 3.0 (1.8) 3.4 (2.1) 0.4 (1.4) 0.397 3.2 (1.7) 4.1 (1.4) 0.9 (1.6) 0.108 0.320 0.328 Phosphate binders (5 points) 3.5 (1.4) 2.3 (1.1) 0.2 (1.3) 0.640 2.2 (1.5) 2.9 (1.1) 0.7 (1.3) 0.111 0.267 0.756 Phosphate metabolism (4 points) 2.6 (1.0) 2.9 (0.8) 0.3 (1.2) 0.465 1.9 (1.2) 2.5 (1.0) 0.6 (1.2) 0.140 0.438 0.600 Total Score (20 points) 11.5 (5) 12.1 (3) 0.6 (3) 0.499 9.8 (5) 11.9 (4) 2.1 (5) 0.189 0.992 0.666 Values are means (SE), analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusted for differences at baseline a – statistically significant at p<0.05 Table 5.6 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Knowledge Test Scores of the Participants at Week 12 SE (n=10) PPS (n=7)

Topic Baseline score

Week 12 score Change p-value

Baseline score

Week 12 score Change p-value

Intergroup baseline p-value

Adjusted Intergroup

week 12 p-value

General (5 points) 2.0 (1.4) 3.0 (1.2) 1.0 (1.4) 0.085 1.9 (1.4) 3.1 (1.4) 1.3 (1.5) 0.063 0.584 0.773 Food content (6 points) 2.8 (2.0) 3.5 (1.3) 0.7 (1.2) 0.089 3.0 (2.0) 4.4 (1.8) 1.4 (2.4) 0.162 0.320 0.215 Phosphate binders (5 points) 3.1 (1.5) 2.9 (1.3) -0.2 (1.0) 0.555 2.0 (1.7) 3.0 (1.4) 1.0 (0.8) 0.018a 0.267 0.071 Phosphate metabolism (4 points) 2.3 (1.3) 2.6 (1.2) 0.3 (1.5) 0.541 1.7 (1.3) 2.6 (0.8) 0.9 (1.2) 0.111 0.438 0.824 Total Score (20 points) 10.2 (5.5) 11.5 (3.8) 1.3 (4) 0.331 8.9 (5.7) 12.9 (4.1) 4 (4.6) 0.060 0.992 0.215 Values are means (SE), analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusted for differences at baseline a – statistically significant at p<0.05

66

Table 5.7 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Satisfaction of the Participants at Week 6 SE (n=11) PPS (n=10) Baseline

score Week 6 score

Change p-value Baseline score

Week 6 score

Change p-value Intergroup Baseline

Adjusted Intergroup

Week 6

My thoughts on food choices (out of 45)

30.1 (4.2) 31.3 (4.4) 1.2 (4.0) 0.355 29.7 (6.5) 29.2 (4.5) -0.50 (4.3)

0.722 0.967 0.230

My thoughts on social aspects of food (out of 20)

13.5 (3.7) 13.3 (4.1) -0.22 (3.4)

0.831 13.0 (4.8) 11.5 (2.7) -1.50 (3.6)

0.224 0.815 0.232

Total Score (out of 65) 43.6 (7) 44.6 (7) 1.0 (7) 0.650 42.7 (11) 40.7 (7) -2 (7) 0.386 0.930 0.169 Values are means (SD), analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusting for differences at baseline a - significant at p<0.05 Table 5.8 Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Satisfaction of the Participants at Week 12 SE (n=11) PPS (n=10) Baseline

score Week 12

score Change p-value Baseline

score Week 12

score Change p-value

Intergroup Baseline

Adjusted Intergroup Week 12

My thoughts on food choices (out of 45)

30.5 (4.5) 33.0 (4.5) 2.5 (4.7) 0.130 31.6 (6.9) 33.5 (7.8) 1.93 (5.8) 0.410 0.967 0.938

My thoughts on social aspects of food (out of 20)

13.7 (3.7) 14.8 (3.3) 1.1 (3.1) 0.287 14.6 (4.7) 13.4 (2.8) -1.1 (3.3) 0.400 0.815 0.163

Total Score (out of 65) 44.2 (7) 48.8 (6) 4.6 (6.3) 0.045a 46.1 (11) 48.4 (11) 2.2 (11) 0.615 0.930 0.715 Values are means (SD), analyzed by Paired t-tests, Independent samples t-tests, Linear regression adjusting for differences at baseline a - significant at p<0.05

67

68

Table 5.9 - Summary of Qualitative Data from Dietary Satisfaction Questionnaires and Follow-up Telephone Calls (n=10) Paraphrased Comments General comments

Positive ! Enjoyed weekly follow-up phone calls ! Appreciated more intensive support

PPS Thoughts Positive ! Enjoyed using, helpful (n=6)

! Finds more freedom with food choices ! Less likely to binge on high phosphorus foods ! Now has a better understanding of what foods are best (n=2) ! Helpful in quantifying phosphorus intake (n=2)

Neutral ! Patient developed own list of food commonly consuming (x2) Negative ! 40 points is too low, difficult target

! Booklet too large ! Hard to find time to record foods and assign points (n=5) ! Processed/ready-to-eat foods hard to use with booklet (n=2) ! Challenging when eating out

Suggestions ! Alphabetical order instead of by food group ! All chicken items have skin-on ! Lacks ethnic and fast food items

69

Table 5.10 - Effect of Standard Education (SE) and the Phosphorus Point System Tool (PPS) on Dietary Intake of Processed Foods Over Time (servings per week)

Servings per week Intergroup differences

SE (mean, SD) PPS (mean, SD) p-value Fast food Baseline 0.52 (1.4) 1.05 (1.8) 0.435 Week 6 0.42 (1.4) 1.19 (1.9) 0.276 Week 12 0.50 (1.6) 1.00 (1.1) 0.508Deli meat Baseline 1.12 (2.0) 0.82 (1.3) 0.369 Week 6 0.69 (1.0) 0.43 (0.5) 0.419 Week 12 0.05 (0.1)* 0.28 (0.5) 0.347Processed cheese Baseline 1.47 (3.2) 0.08 (0.2) 0.141 Week 6 0 0.09 (0.2) 0.247 Week 12 0 0 Boxed/frozen meats Baseline 0.15 (0.4) 0.37 (0.7) 0.383 Week 6 0.21 (0.7) 0.33 (0.5) 0.663 Week 12 0.06 (0.2) 0.20 (0.4) 0.322Canned fish Baseline 0.14 (0.3) 0.24 (0.4) 0.504 Week 6 0.10 (0.3) 0.33 (0.4) 0.186 Week 12 0.15 (0.3) 0.36 (0.6)* 0.373Pudding Baseline 0 0.02 (0.1) 0.343 Week 6 0 0 0 Week 12 0.13 (0.3) 0 0.358Muffins Baseline 0.42 (1.4) 1.03 (2.8) 0.509 Week 6 0 1.72 (2.7) 0.088 Week 12 0.10 (0.3) 2.17 (3.5) 0.207Cake Baseline 0.33 (1.1) 0.08 (0.2) 0.478 Week 6 0.21 (0.6) 0.36 (0.7) 0.567 Week 12 0.15 (0.5) 0.63 (1.0) 0.206Cookies Baseline 0.46 (0.9) 2.33 (5.6) 0.324 Week 6 0.79 (2.2) 0.89 (1.6) 0.910 Week 12 0.33 (1.0) 1.08 (2.2) 0.382Cola Baseline 0.48 (1.1) 1.75 (4.4) 0.327 Week 6 0.25 (0.6) 0.83 (2.3) 0.392 Week 12 0.30 (0.7) 0.42 (0.8) 0.759TOTAL SERVINGS PER WEEK

Baseline 7.79 (8.6) 8.89 (7.8) 0.757 Week 6 4.65 (4.2) 6.76 (4.5) 0.282 Week 12 2.00 (2.3)* 6.01 (4.3) 0.034a

Values are means (SD), analyzed by Independent samples t-test, Paired t-tests a - significant when p<0.05 * - indicates a trend approaching significance, within group, when p<0.10

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5.4.5 Processed food intake

Weekly servings of processed foods reported at each of the three time points indicated

that at week 12, the mean number of total servings of processed food was significantly higher in

the PPS group compared to the control group, Table 5.10. The SE group consumed

approximately 8 servings of processed foods per week, and the PPS group consumed 9 servings

per week at baseline. At week 12, the SE group had reduced this intake to 2 servings per week,

with the PPS group consuming 6 servings per week. These results were unintended. When

looking at differences between groups and within groups based on individual processed food

items there were no significant differences.

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6.0 Discussion

6.1 Serum Phosphorus Levels

The primary objective of this study was to determine the effectiveness of the Phosphorus

Point System© Tool (PPS) in reducing serum phosphorus levels in hyperphosphatemic

participants with CKD. In patients with CKD, serum phosphorus is affected by renal function,

consumption of phosphate binders and dietary intake of phosphorus.

Although the PPS did not have a significant effect on reducing serum phosphorus levels

over time, or when compared to the Standard Education (SE) group; there was a trend indicating

that the PPS may have an effect on reducing serum phosphorus, based on linear regression and

adjusting for serum phosphorus at baseline. We set out with the intention of reducing serum

phosphorus by 0.35 mmol/L, and based upon the linear regression confidence interval of (-0.366

to 0.053) it appears as though we have not excluded our planned size effect. No conclusions

can be made on whether the same results would be seen with a larger sample size. When a

sample size calculation was completed based upon the serum phosphorus results seen in this

study, a sample size of 31 participants per group, a total of 62, would be required.

Other studies involving a dietary intervention to reduce serum phosphorus levels in

patients with pre-dialysis chronic kidney disease have not been completed to our knowledge.

Thus we do not have comparable research to which we can relate whether a dietary intervention

study would show significant changes in serum phosphorus within this population.

Various studies conducted in dialysis patients with educational strategies to reduce

dietary phosphate intake have been completed; and mixed effects of these strategies have been

seen. Morey et al. (2008) found that advanced monthly counseling aimed at reducing dietary

phosphate intake and improving binder compliance reduced serum phosphorus significantly

from baseline to 3-months in the intervention hemodialysis group (2.05±0.48 to 1.80±0.48

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mmol/L, p=0.003, n=30), however these lower levels were not sustained at 6-months (1.90±0.43

mmol/L, p=0.081). A study involving education focused on reducing phosphorus intake while

maintaining protein intake, thus lowering phosphorus-protein ratios, found there was a trend for

reducing serum phosphorus levels but this was not statistically significant (2.29±0.34 to

2.13±0.52 mmol/L, n=20) (23). Schlatter and Estwing Ferrans (1998) found that providing a

one-time innovative dietary phosphorus educational intervention to the study group did not

significantly reduce serum phosphorus levels 3 months after the teaching intervention

(2.06±0.40 to 2.00±0.36 mmol/L, p=0.50, n=29). Alternatively, Ford et al (2003) found

improved serum phosphorus and calcium phosphate product after 6 months within the

experimental group with additional monthly dietary phosphorus education (Phosphorus:

2.20±0.23 to 1.68±0.39, p=0.0001, n=32). Sun et al. (2008) saw significant reductions in serum

phosphorus levels one month after receiving more intensive education pertaining to dietary

phosphorus where participants were provided a test related to phosphorus and had to complete

the test as many times as necessary until a perfect score was achieved (2.38±0.39 to 2.16±0.63,

p=0.034, n=50). Significant reductions in serum phosphorus within the intervention group was

seen 3 months after more intensive dietary phosphorus education was provided on one occasion

(1.96 to 1.60 mmol/L, p=0.02, n=29) (24). As well, the preliminary study completed with the

PPS in peritoneal dialysis outpatients found that after one month of using the PPS tool, serum

phosphorus levels decreased significantly (1.65 to 1.45 mmol/L, p=0.019, n=10) (77).

We speculate that decreased dietary phosphorus intake would have a greater impact on

serum phosphorus levels in patients with end stage renal disease requiring dialysis versus CKD

patients with residual renal function, as serum phosphorus may be more sensitive to dietary

changes in those on dialysis. There have yet to be studies looking at the effect of dietary

phosphorus restriction on serum phosphorus levels in the pre-dialysis population. We attempted

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to answer this question, however were unable to reach a sufficient sample size to show whether

an effect existed or not.

Thus, further research is required to determine if dietary modulation has an effect on

improving phosphorus levels and long-term outcomes in patients with pre-dialysis CKD as well

as in dialysis patients as the results are, as of yet, inconclusive.

6.2 Renal function

There were no significant changes in renal function within the participants at each of the

three time points. Thus, we can state that there was no effect on serum phosphorus levels that

could be attributed to changes in renal function. The patients were all at varying stages of renal

function when they started the study, and thus they may have had differing levels of renal

phosphorus excretion which in turn affects serum phosphorus levels. Thus, this could relate to

an underlying challenge of studying this population, compared to the dialysis patient population

who do not have residual renal function to affect their renal excretion of phosphorus. However,

we did not measure the rate of renal phosphorus excretion in this study.

6.3 Phosphate binders

Phosphate binder consumption data collected from the repeat 24-hour recalls indicated

there were no significant differences over time within the groups, or between the groups at any

time points. Thus, we can conclude that the phosphate binders did not appear to have an effect

on serum phosphorus levels during the study period. If binder consumption had increased, this

could have been thought to be the cause of the trend of decreasing serum phosphorus, however

this was not apparent.

6.4 Dietary Intake

We found that based upon mean 2-day 24-hour dietary recalls using the 5-step multiple

pass repeat 24-hour recall method, the participants in the PPS group appeared to have

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significantly decreased their intake of phosphorus at week 6. This same finding was not seen at

week 12. We speculate that since the participants were told they were no longer required to

track the number of daily phosphorus points consumed after week 6, that participants may have

become more lenient in their intake of phosphorus and not adhered as strictly to the point system

diet. Although there was no significant change in dietary phosphorus intake between week 6

and week 12 in the PPS group, it was seen that 25% of the PPS participants had mean

phosphorus intakes greater than 1000mg at week 12, compared to 0% at week 6. The reason for

allowing participants the option of no longer tracking daily point intake is that we hoped

learning would occur and participants would have established a dietary intake pattern by week 6

that had been adopted based on their use of the tool.

The decrease in dietary phosphorus intake at week 6 appears to be linked to a decreased

consumption of phosphorus-rich protein foods, as there is also a significant decrease in dietary

protein intake at week 6 in the PPS group compared to the SE group. This however, does not

seem to have a significant effect on serum phosphorus levels at week 6. We speculate that

serum phosphorus levels of pre-dialysis CKD patients may not be as sensitive to changes in

dietary phosphorus intake compared to hemodialysis patients; however, no research has been

done to support this. Metabolic studies looking into the effect of restricting dietary phosphorus

intake on serum phosphorus levels have yet to be completed in predialysis patients, and would

provide valuable insight into the results of the current study.

At week 12, it was seen that the phosphorus-protein ratio was significantly higher in the

PPS group compared to baseline, and also in the PPS group at week 12 compared to SE group.

This could be attributed to the higher weekly intake of processed foods, which are higher in

phosphorus compared to non-processed foods. This may be a possible explanation for the

reason we do not see a significant decrease in serum phosphorus in the PPS group at week 12, as

there continues to be a trend of both decreasing intake of phosphorus and protein in the PPS

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group at week 12. When looking at the reported dietary intakes from the repeated 24-hour

recalls at week 12, the PPS group consumed an average of 1.6 servings of processed foods over

the 2 days, compared to the SE group who consumed an average of 0.9 servings. Processed

foods, however, were not consumed more frequently than foods known to be the main sources

of dietary phosphorus such as meats, dairy, cheese. However, as stated by Calvo (2000) there is

no way for us to know the magnitude of phosphorus within the processed food items, despite

that they were consumed in lower amounts than foods naturally occurring in phosphorus, and

their contribution to total dietary phosphorus load consumed is unknown (62).

The cessation of the intensive dietary education and support at week 6, may have had an

impact on the dietary intake and thus may explain the lack of significant dietary results at week

12. The reason for allowing participants to no longer record daily intake, is that we had hoped

learning would have occurred and that daily point tracking would no longer be required.

Intensive support via weekly phone calls past week 6 would not be feasible in a clinical setting.

Dietary intake of potassium was significantly lower at week 6 and week 12 compared to

baseline in the PPS group. We speculate that this could be related to the fact that foods high in

potassium are highlighted within the PPS tool, and learning may have occurred where patients

may have become more knowledgeable about foods that are high in potassium, and

subsequently avoided them. Additionally, it was seen in a study by Pollock & Jaffery (2007)

that when hemodialysis and peritoneal dialysis patients receiving routine renal dietary education

are administered a questionnaire testing their knowledge of nutrients specific to the renal diet,

patients were found to have increased scores on the questions pertaining to potassium, sodium

and protein compared to questions surrounding phosphorus. Thus the patients may have a

greater aptitude for retaining knowledge of foods rich in dietary potassium versus foods rich in

phosphorus. It is also possible that the patients may have been more willing to avoid potassium-

76

rich foods over those rich in phosphorus, as phosphorus is more wide-spread throughout the

diet, and thus this is reflected in the dietary intake.

Weight and BMI both decreased in the PPS group at week 6, and this could be attributed

to the fact that 46% of the group was categorized as obese and many had expressed an interest in

weight loss when the study was initiated. Although the patients were informed the study was

not intended for achieving weight loss, the effect of being asked to record one’s daily intake for

6-weeks could have resulted in a reduction of energy intake. However, there were no significant

differences evident with respect to energy intake.

Despite both a significant decrease in dietary phosphorus intake and a significant

decrease in weight in the PPS group compared to SE at week 6, there was not a significant

decrease in serum phosphorus levels at week 6. The previously mentioned speculation of

whether the pre-dialysis population has the same level of sensitivity as the hemodialysis

population to show changes in serum phosphorus levels is once again raised here.

Additionally, serum levels of alkaline phosphatase (ALP) were measured, as a reflection

of the release of calcium from bone. ALP was not significantly influenced by the education

provided and did not appear to be influenced by diet. ALP levels in both groups were within

normal limits, indicating that the release of calcium from the bone was not occurring at a level

of concern in this group.

6.5 Phosphorus Knowledge

There were no significant differences in overall knowledge score or knowledge scores

related to food sources of phosphorus within or between groups. The improvements within the

PPS group in total score and scores related to general phosphate management did not reach

significance. The phosphorus knowledge scores were still quite low, despite receiving intensive

education. Mean total scores at week 6 and week 12 in the PPS group were 11.9 (SD=4) out of

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20 and 12.9 (SD=4) out of 20, respectively. This is comparable to the study by Ford et al (2003)

in which this questionnaire was developed, as 6-months after receiving monthly dietary

phosphorus education the participants answered 68.7% of the questions correctly. The mean

score at week 12 in our study corresponds to having 64.5% correct answers. This could be

related to the idea that phosphorus knowledge is poor despite receiving regular dietary teaching,

as also seen by Pollock (2007). Patients with hyperphosphatemia may require even more

frequent education from the dietitian to grasp the concepts related to hyperphosphatemia

management.

6.6 Dietary Satisfaction

Satisfaction scores were higher at week 12 compared to baseline in the SE group, which

is not aligned with our hypothesis. However, there were no significant differences between the

PPS group and the SE group in satisfaction scores. The improvements seen in the SE group

were higher than those in the PPS group, as the SE group had lower scores at baseline. We

intended for the PPS group to have higher satisfaction, as the PPS tool allows greater dietary

flexibility. We speculate that possibly the participants in the PPS group were more aware of the

need for following the dietary modification more intensely, since they had to record daily intake

to track the points, and thus felt more pressure to adhere to the diet than those in the SE group,

leading to less of an improvement in satisfaction.

The Modification of Diet in Renal Disease (MDRD) study found that as participants

were assigned to either a low-protein diet or very low-protein diet, the participants’ satisfaction

declined. They stated that the differences in satisfaction could be related to the difference of the

diet compared to the usual eating pattern of typical Americans. This idea could also be

transferred to our study population. Since the participants are of a mean age of 56 in the PPS

group and 53 in the SE group, participants have been eating a certain dietary pattern for most of

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their adult lives, and any change to this pattern may be perceived as a disruption in their typical

habits, thus leading to poorer satisfaction. Although the PPS group was permitted to include

more food items, as long as they met the point limit, the participants may not have been as

satisfied as compared to if they were permitted to consume their ‘regular’ diet.

6.7 Qualitative data

Participants were found to have both positive and negative remarks surrounding the PPS

tool. The main positive remarks state that the users enjoyed the tool and felt as though they had

learned from the tool and would use again. Negative remarks indicated that the tool was time-

consuming to use, and required the inclusion of more ready-to-eat, processed food items as well

as ethnic food items. Suggestions included organizing the food items via alphabetical name

versus food group.

Since half of the participants’ remarks indicated the tool was time consuming to use, this

raises interest surrounding the applicability and feasibility of the PPS tool. Although six of ten

comments indicated the participants enjoyed the tool and found it helpful, it may not be used to

its intended effect if participants aren’t taking the time to records points daily. If the tool was

tested with a larger sample size and an effect on serum phosphorus levels not seen, this would

raise the question of whether its use should be continued.

6.8 Processed Foods

Despite receiving education regarding limiting the intake of processed foods, we found

that the PPS group consumed significantly more servings of processed foods per week at the 12-

week data collection point. The decrease in the number of servings of processed food from

baseline to week 12 was not as large in the PPS group as compared to the SE group. It is

thought that perhaps, since all of the participants who enrolled in the study were eager to learn a

new form of dietary modulation, those who were in the SE group and received the new

79

education about avoiding processed foods, took the advice readily and modified that behaviour

more than those in the PPS group who had a different priority for dietary modulation, focusing

more specifically on tracking phosphorus points. Both groups received education about

avoiding processed foods due to the high bio-availability of phosphorus additives, via a handout

developed for the study, as excluding the SE group from this education was thought to be

unethical. The current version of the PPS tool does not discourage the consumption of

processed foods.

Additionally, the point values for the phosphorus content of foods within the PPS tool

are based upon the nutrient composition tables of the USDA database and the Canadian Nutrient

File (CNF). A study done by Sullivan (2007) indicates that there are discrepancies between the

actual content of phosphorus in chicken products containing phosphorus additives based on

laboratory analyses versus those values in the ESHA Food Processor Software, which obtains

it’s values from the USDA database (59). Studies of this nature have not been completed in

Canada, however when our study group looked into the phosphorus content of foods within the

CNF, it was found that many of the phosphorus values in the CNF did not differ from those in

the USDA database, and thus similar issues related to phosphorus additives likely exist in

Canada.

It was found via chemical analyses in 1988, that routine methodology underestimated

actual daily phosphorus intake by 272 mg, and if the diet contained more restaurant or

convenience foods than average, the value increase to 387 mg per day (94). This has likely

expanded with the increase in convenience foods currently on the market.

Thus, participants following the PPS tool and adhering to the recommendation of 40

points may in fact be consuming more phosphorus than we are aware of, as it is not known

whether other foods containing phosphorus additives are accurately represented within the

nutrient composition tables.

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A study by Sullivan et al. (2009) found that providing dietary education specifically

focused on food additives resulted in a significant improvement in the change in serum

phosphorus levels between the groups, in participants on hemodialysis (95). The education

provided focused on a one-time teaching where 30 minutes of education was provided focusing

on additives, and a handout on fast-food restaurants was given listing specific items to avoid as

they contained additives. Thus, this may account for the reason why we do not see a difference

in serum phosphorus levels between the groups, as both groups in our study were given the

education related to phosphorus additives.

There is a need to quantify the phosphorus content of processed and fast food items

which contain phosphorus additives, in order to better evaluate the dietary intake of phosphorus

and put this method of assessing compliance to a low-phosphorus diet to better use within this

population. It may be beneficial if the phosphorus content of foods was presented on the food

label, so that all consumers could be aware. The National Kidney Foundation Council on Renal

Nutrition and the American Dietetic Association Renal Practice Group began advocating in

2006 for the reinstatement of phosphorus content of the nutrition label of foods in the United

States (61). Among the challenges that presented itself was the question about how organic and

inorganic phosphate content would be differentiated, considering they are absorbed differently;

and requiring food companies to perform this analysis was considered too great of a request

(61). It appears as though the addition of the phosphate content on food labels is far from being

integrated into current practice.

6.9 Limitations

We were unable to meet the study’s intended sample size, despite including a second site

into our recruitment strategy. There may be a greater effect of the tool evident with a larger

sample size, or the tool may appear ineffective with a larger sample.

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The possibility of a discrepancy between the actual phosphorus content of foods

containing phosphorus additives and the content listed within food composition tables, as

demonstrated by Sullivan et al. (2007) could result in an unintended increased consumption of

dietary phosphorus. This could in turn affect serum phosphorus levels, as phosphorus additives

are highly bio-available (11,54,62). This could have affected our ability to see significant

decreases in serum phosphorus , as dietary intakes of phosphorus may not have been within the

target range as previously thought.

We also speculate whether this population may be challenging to study, as the

participants had various levels of renal function at study onset, which in turn affects renal

phosphate excretion. Since renal function varied across the participants, and the rate at which

renal function declines is individual in nature, the effect the intervention may have had on

reducing serum phosphorus levels could have been affected by an unmeasured difference in the

participants’ ability to excrete phosphorus in the urine. This issue could possibly be resolved

with a change in the study design to involve end-stage renal disease patients on hemodialysis

instead of pre-dialysis CKD patients.

The tool itself may have limitations for its integration into clinical practice. As was

seen, 50% of participants found it challenging to find time to track phosphorus points daily, and

this is an essential component that is required for the tool to function as intended. The

qualitative reviews of the tool fuel speculations whether the tool can be simplified in any way to

improve its usability. However, it appears as though the tool was useful for reducing the intake

of potassium. Since those foods high in potassium are shaded, a concept similar to this may be

effective for phosphorus-rich foods. The tool may be more effective if foods were colour-

coded, possibly through a traffic light colour-coding system, to further simplify its use.

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We also cannot rule out the possibility of participant underreporting of dietary intake,

despite using the 5-pass multiple measures repeated 24-hour recall. Patients with CKD often

experience uremia symptoms which impact the quantity and types of foods consumed, and

therefore if the patients were feeling unwell on some occasions this may have affected their

mean 2-day dietary data. However, the 2-day mean energy intakes were not significantly

different, and thus it is unlikely that an effect of selective underreporting would be affecting our

results. Collecting weighed dietary records from the participants may have been more

satisfactory in gaining a true representation of phosphorus intake, over collecting repeat 24-hour

dietary recalls. However the burden of having study participant weigh and record their food

consumed was deemed too large in addition to recording intake for the tool, and thus the

collection of dietary recalls was completed. Twenty-four hour dietary recalls were also used to

collect dietary intake information in Health Canada’s Canadian Community Health Survey in

2002.

6.10 Future Directions

Metabolic studies in predialysis patients looking at serum phosphorus levels and the

response of these levels to dietary phosphorus restriction are necessary. It may be beneficial to

have a better understand of the metabolic response of these patients to dietary restriction before

continuing investigations of effectiveness of dietary education with this stage of disease.

Changing the study design to involve hemodialysis or peritoneal dialysis patients rather than

CKD patients, may be more effective for evaluating the effects of the tool. Hemodialysis

patients are in renal failure, and therefore have very little, if at all, residual renal function. By

using this population we may have a greater ability to ascertain the effects of the tool and

remove the possible confounding effects of renal phosphorus excretion.

83

The integration of collecting urinary phosphorus excretion and correcting for creatinine,

may be beneficial in future studies to be able to verify dietary intake. Additionally, collecting

urinary phosphorus would be useful to determine renal phosphorus excretion within the

participants. Collecting urinary protein and urinary creatinine excretion may also be

informative to identify the effect of the residual renal function on these parameters along with

urinary phosphorus.

Despite the more intensive and frequent education provided to the PPS group,

knowledge scores did not improve significantly. Perhaps more frequent in-person education

with the dietitian would result in improvements in phosphorus knowledge of this group, rather

than over the telephone as done in this study.

Another possible use for the tool would involve the titration of phosphate binder to the

point values for non-processed foods within the tool, of which the accuracy of the point values

we can be quite certain. Patients would then be able to adjust their intake of phosphate binders

according to the phosphorus load of their meals.

If the tool was found effective in a larger sample size within this population, or in the

hemodialysis population, the effects of the tool in long-term studies on other outcomes besides

serum phosphorus levels would be recommended. Longer term studies involving the tool could

also measure the effect of the PPS on reducing complications of hyperphosphatemia, such as

cardiovascular calcification and metastatic calcification, measured via CT-scans. Additionally,

as it is stated that serum phosphorus levels impact the flux of calcium in and out of bone, a long-

term study looking at the effects of the PPS on reducing dietary phosphorus intake and it’s effect

on bone density could be completed with the use of dual energy x-ray absorptiometry.

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7.0 Conclusions

Further research is required to determine whether the Phosphorus Point System© Tool is

effective at reducing serum phosphorus levels in patients with pre-dialysis CKD. Although

there was a trend indicating the PPS tool may reduce serum phosphorus levels, no conclusions

about its effectiveness can be drawn from this study. Our hypothesis of a reduction in serum

phosphorus in the group receiving the PPS education could not be supported by our research.

Whether a larger study with the Phosphorus Point System© Tool in the pre-dialysis

population is appropriate, is yet to be determined, as we question the ability of the intervention

to demonstrate significant results in a population that has residual renal function. Further

metabolic studies looking at the effects of dietary phosphorus restriction on serum phosphorus

levels in predialysis chronic kidney disease patients are required.

We hypothesized that adherence to the PPS tool would result in a decrease in dietary

phosphate intake. Dietary phosphate and protein intake were reduced at week 6 in the group

educated using the Phosphorus Point System Tool©. This did not result in a reduction in serum

phosphorus levels within this group at week 6, and this may be related to the fact that nutrient

composition tables used for dietary analyses likely do not accurately account for phosphorus

additives and the quantity of phosphorus within foods containing these additives. This in turn

would limit the effectiveness of the PPS tool, as the point values within the tool are based on

data from nutrient composition tables.

Phosphorus knowledge test scores remained low in the group that received more

intensive education, despite our hypothesis of improved knowledge surrounding dietary

phosphorus in the group receiving the PPS education. This lack of improvement in knowledge

85

seems to be common, as demonstrated in other studies, indicating that CKD patients may be less

able to retain knowledge pertaining to phosphorus compared to other nutrients.

Satisfaction levels were not improved in the participants using the PPS tool, despite our

hypothesis that the tool would allow for greater dietary flexibility and thus in turn improve

satisfaction. When comparing a low-phosphorus diet to a standard diet, it is logical that

satisfaction would be lower and thus it may not matter to what degree we modify the renal diet,

satisfaction may only be increased if the participants were able to consume their typical regular

diet that they consumed before a diagnosis with kidney disease.

We have not ruled out a possible effect of the PPS in reducing serum phosphorus levels,

and further study with a larger population and perhaps in a patient population with consistent

renal function, such as the hemodialysis population is warranted. It is yet to be demonstrated

whether the serum phosphorus levels of patients with pre-dialysis chronic kidney disease

respond to dietary phosphorus intervention. Metabolic studies investigating the effects of

dietary phosphorus restriction on serum phosphorus levels in predialysis patients are required.

However, the need for adequate phosphorus control in this population is known, as evidence

indicates pre-dialysis patients and patients new to dialysis appear to have coronary calcification

associated with hyperphosphatemia at earlier stages than previously thought, and this in turn

increases the risk of morbidity and mortality (39,41,96).

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8.0 References

(1) Knochel J. Chapter 8: Phosphorus. In: Shils ME, Olson JA, Shike M, Ross AC, editors. Modern nutrition in health and disease. 9th ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 1999. p. 157-167.

(2) Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. American Journal of Kidney Diseases 2000;35(6):1226-1237.

(3) Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney International 2007;71:438-441.

(4) Barsotti G, Cupisti A. The role of dietary phosphorus restriction in the conservative management of chronic renal disease. Journal of Renal Nutrition 2005;15(1):189-192.

(5) The Kidney Foundation of Canada. Living with Kidney Disease. 4th edition ed.; 2006.

(6) The Kidney Foundation of Canada. Facing the Facts - Winter 2009. Available at: http://www.kidney.ca/files/Kidney/aaFacing_the_Facts_Winter_2009_KRESCENT.pdf. Accessed Mar 20, 2009.

(7) Mushnick R. MedlinePlus Medical Encyclopedia: end-stage kidney disease. 2005; Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000500.htm. Accessed 07/04, 2007.

(8) Chauhan T. End-stage renal disease patients up nearly 19%. Canadian Medical Association Journal 2004;170(7):1087.

(9) Kopple JD. Chapter 89. Renal Disorders and Nutrition. In: Shils ME, Olson JA, Shike M, Ross AC, editors. Modern nutrition in health and disease. 9th ed. Philadelphia, Pennsylvania: Lippencott, Williams & Wilkins; 1999. p. 1439-1472.

(10) Kopple JD. Chapter 23: Nutritional management of nondialyzed patients with chronic renal failure. In: Kopple JD, Massry SG, editors. Nutritional management of renal disease. 2nd ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2003. p. 379.

(11) Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Seminars in Dialysis 2007;20(4):295-301.

(12) Albaaj F, Hutchison AJ. Hyperphosphatemia in Renal Failure: Causes, consequences, and current management. Drugs 2003;63(6):577-496.

(13) O'Callaghan CA, Brenner BM. Kidney at a glance. Williston, Vermont: Blackwell Publishing; 2000.

(14) Slatopolsky E, Bricker NS. The role of phosphorus restriction in the prevention of secondary hyperparathyroidism in chronic renal disease. Kidney International 1973;4(2):141-145.

(15) Uribarri J, Calvo MS. Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Seminars in Dialysis 2003;16(3):186-188.

(16) Statistics Canada. Canadian Community Health Survey, Cycle 2.2 (Nutrition). 2004.

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(17) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Institute of Medicine. Phosphorus. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride Washington, D.C.: National Academy Press; 1997. p. 174-176, 187.

(18) Ford J, Pope JF, Hunt AE, Gerald B. The effect of diet education on the laboratory values and knowledge of hemodialysis patients with hyperphosphatemia. Journal of Renal Nutrition 2004;14(1):36-44.

(19) Hsu C, Chertow GM. Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency. Nephrology Dialysis Transplantation 2002;17:1419-1425.

(20) Friedman EA. Consequences and management of hyperphosphatemia in patients with renal insufficiency. Kidney International 2005;67(S95):S1-S7.

(21) Goodman WG. Calcium and phosphorus metabolism in patients who have chronic kidney disease. Medical Clinics of North America 2005;89:631-647.

(22) Locatelli F, Cannata-Andia JB, Drueke TB, Horl WH, Fouque D, Heimburger O, et al. Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphatemia. Nephrology Dialysis Transplantation 2002;17:723-731.

(23) Cupisti A, D'Alessandro C, Baldi R, Barsotti G. Dietary habits and counseling focused on phosphate intake in hemodialysis patients with hyperphosphatemia. Journal of Renal Nutrition 2004;14(4):220-225.

(24) de Brito Ashurst I, Dobbie H. A randomized controlled trial of an educational intervention to improve phosphate levels in hemodialysis patients. Journal of Renal Nutrition 2003;13(4):267-274.

(25) Cupisti A, Morelli E, D'Alessandro C, Lupetti S, Barsotti G. Phosphate control in chronic uremia: don't forget diet. Journal of Nephrology 2003;16:29-33.

(26) Lumertgul D, Burke TJ, Gillum DM, Alfrey AC, Harris DC, Hammond WS, et al. Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Kidney International 1986;29:658-666.

(27) Coladonato JA. Control of hyperphosphatemia among patients with ESRD. Journal of the American Society of Nephrology 2005;16:S107-S114.

(28) Nakajima K, Umino K, Azuma Y:K, S., Takano K, Obara T, Sato K. Stimulating parathyroid cell proliferation and PTH release with phosphate in organ cultures obtained from patients with primary and secondary hyperparathyroidism for a prolonged period. Journal of Bone Mineralism and Metabolism 2009;27:224-233.

(29) Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium X phosphate product with mortality risk in chronic hemodialysis patients: a national study. American Journal of Kidney Diseases 1998;31(4):607-617.

(30) Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO4, CaxPO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis. Journal of the American Society of Nephrology 2001;12:2131-2138.

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(31) Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. Journal of the American Society of Nephrology 2005;16:520-528.

(32) Llach F, Forero FV. Secondary hyperparathyroidism in chronic renal failure: pathogenic and clinical aspects. American Journal of Kidney Diseases 2001;38(S5):S20-S33.

(33) Cupisti A, Aparicio M, Barsotti G. Potential benefits of renal diets on cardiovascular risk factors in chronic kidney disease patients. Renal Failure 2007;29:529-534.

(34) Poduval RD, Wolgemuth C, Ferell J, Hammes MS. Hyperphosphatemia in dialysis patients: is there a role for focused counseling? Journal of Renal Nutrition 2003;13(3):219-223.

(35) Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. American Journal of Kidney Diseases 1998;32(Supplement 3):S112-S119.

(36) Wexeler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddhai J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. Circulation 1996;94(1175-1192).

(37) Amann K, Gross ML, London GM, Ritz E. Hyperphosphatemia-a silent killer of patients with renal failure? Nephrology Dialysis Transplantation 1999;14:2085-2087.

(38) Ribeiro S, Ramos A, Brandao A, Rebelo JR, Guerra A, Resina C, et al. Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. Nephrology Dialysis Transplantation 1998;13:2037-2040.

(39) Spiegel DM, Raggi P, Mehta R, Lindberg JS, Chonchol M, Ehrlich J, et al. Coronary and aortic calcifications in patients new to dialysis. Hemodialysis International 2004;8:265-272.

(40) Russo D, Palmiero G, DeBlasio AP, Balletta MM, Andreucci VE. Coronary artery calcification in patients with CRF not undergoing dialysis. American Journal of Kidney Diseases 2004;44(6):1024-1030.

(41) Tomiyama C, Higa A, Dalboni MA, Cendoroglo M, Draibe SA, Cuppari L, et al. The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients. Nephrology Dialysis Transplantation 2006;21:2464-2471.

(42) Nishizawa Y, Shoji T, Kawagishi T, Morri H. Atherosclerosis in uremia: possible roles of hyperparathyroidism and intermediate density lipoprotein accumulation. Kidney International 1997;62:s90-s92.

(43) Jindal K, Chan CT, Deziel C, Hirsch D, Soroka SD, Tonelli M, et al. CSN Hemodialysis Clinical Practice Guidelines Chapter 3: Mineral Metabolism. Journal of the American Society of Nephrology 2006;17:S1-S27.

(44) National Kidney Foundation I. Guideline 4. Restriction of dietary phosphorus in patients with CKD. 2003.

(45) Bailie G, Massry SG. Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease: An Overview. Pharmacotherapy 2005;25(12):1687-1707.

(46) National Kidney Foundation I. Guideline 5. Use of phosphate binders in CKD. 2003.

(47) Malluche HH, Mawad H. Management of hyperphosphatemia of chronic kidney disease: lessons from the past and future directions. Nephrology Dialysis Transplantation 2002;17:1170-1175.

89

(48) Salusky IB. A new era in phosphate binder therapy: what are the options? Kidney International 2006;70:s10-s15.

(49) Nolan CR, Quinbi WY. Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Kidney International 2005;67(s95):s13-s20.

(50) Minutolo R, Bellizzi V, Cioffi M, Iodice C, Giannattasio P, Andreucci M, et al. Postdialytic rebound of serum phosphorus: pathogenetic and clinical insights. Journal of the American Society of Nephrology 2002;13:1046-1054.

(51) DeSoi CA, Umans JG. Phosphate kinetics during high-flux hemodialysis. Journal of the American Society of Nephrology 1993;4:1214-1218.

(52) Mucsi I, Hercz G, Uldall R, Ouwendyk M, Francoeur R, Pierratos A. Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis. Kidney International 1998;53:1399-1404.

(53) National Kidney Foundation I. Guideline 3. Evaluation of serum phosphorus levels. 2003.

(54) Calvo MS, Park YK. Changing phosphorus content of the U.S. diet: potential for adverse effects on bone. The Journal of Nutrition 1996;126(4S):1168S-1180S.

(55) Murphy-Gutekunst L. Hidden phosphorus in popular beverages: part 1. Journal of Renal Nutrition 2005;15(2):e1-e6.

(56) Karalis M, Murphy-Gutekunst L. Enhanced foods: hidden phosphorus and sodium in foods commonly eaten. Journal of Renal Nutrition 2006;16(1):79-81.

(57) Murphy-Gutekunst L, Barnes K. Hidden phosphorus at breakfast: part 2. Journal of Renal Nutrition 2005;15(3):e1-e6.

(58) Murphy-Gutekunst L, Uribarri J. Hidden phosphorus-enhanced meats: part 3. Journal of Renal Nutrition 2005;15(4):e1-e4.

(59) Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients. Journal of Renal Nutrition 2007;17(5):350-354.

(60) Sherman RA. Dietary phosphate restriction and protein intake in dialysis patients: a misdirected focus. Seminars in Dialysis 2007;20(1):16-18.

(61) Murphy-Gutekunst L. Hidden Phosphorus: Where do we go from here? Journal of Renal Nutrition 2007;17(4):e31-e36.

(62) Calvo MS. Dietary considerations to prevent loss of bone and renal function. Nutrition 2000;16(7/8):564-566.

(63) Sarathy S, Sullivan C, Leon JB, Sehgal AR. Fast food, phosphorus-containing additives, and the renal diet. Journal of Renal Nutrition 2008;18(5):466-470.

(64) Slatopolsky E, Finch J, Denda M, Ritter C, Zhong M, Dusso A, et al. Phosphate restriction prevents parathyroid gland growth. Journal of Clinical Investigation 1996;97(11):2534-2540.

(65) Kusano K, Segawa H, Ohnishi R, Fukushima N, Miyamoto K. Role of low protein and low phosphorus diet in the progression of chronic kidney disease in uremic rats. Journal of Nutritional Science and Vitaminology 2008;54:237-243.

90

(66) Marchais SJ, Metivier F, Guerin AP, London GM. Association of hyperphosphataemia with haemodynamic disturbances in end-stage renal disease. Nephrology Dialysis Transplantation 1999;14:2178-2183.

(67) Lowrie EG, Lew NL. Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. American Journal of Kidney Diseases 1990;15:458-482.

(68) Greene SV, Falciglia G, Rademacher R. Relationship between serum phosphorus levels and various outcome measures in adult hemodialysis patients. Journal of Renal Nutrition 1998;8:77-82.

(69) Gilles BP, Caggiula AW, Chiavacci AT, Coyne T, Doroshenko L, Milas NC, et al. Nutrition intervention program of the Modification of Diet in Renal Disease: a self-management approach. Journal of the American Dietetic Association 1995;95(11)(1288-1294).

(70) Cianciaruso B, Pota A, Pisani A, Torraca S, Annecchini R, Lombardi P, et al. Metabolic effects of two low protein diets in chronic kidney disease stage 4-5 -- a randomized controlled trial. Nephrology Dialysis Transplantation 2008;23:636-644.

(71) Kirkpatrick DL. Evaluating Training Programs. 2nd Edition ed. San Francisco: Berrett Koehler; 1959.

(72) Shaw-Stuart NJ, Stuart A. The effect of an educational patient compliance program on serum phosphate levels in patients receiving hemodialysis. Journal of Renal Nutrition 2000;10(2).

(73) Schlatter S, Estwing Ferrans C. Teaching program effects on high phosphorus levels in patients receiving hemodialysis. American Nephrology Nurses' Association 1998;25(1):31-36.

(74) Sun C, Chang K, Chen S, Chang C, Wu M. Patient education: An efficient adjuvant therapy for hyperphosphatemia in hemodialysis patients. Renal Failure 2008;30:57-62.

(75) Yokum D, Glass G, Cheung CF, Cunningham J, Fan S, Madden AM. Evaluation of a phosphate management protocol to achieve optimum serum phosphate levels in hemodialysis patients. Journal of Renal Nutrition 2008;18(6):521-529.

(76) Morey B, Walker R, Davenport A. More dietetic time, better outcome? Nephron Clinical Practice 2008;109:c173-c180.

(77) Nasih L, Huumo N, Darling P, McFarlane P, Huang C. Evaluation of a revised phosphorus point system as a teaching tool for improving dietary adherence and satisfaction in an outpatient peritoneal dialysis population. 2006.

(78) Pollock JB, Jaffery JB. Knowledge of phosphorus compared with other nutrients in maintenance dialysis patients. Journal of Renal Nutrition 2007;17(5):323-328.

(79) Thomas LK, Sargent RG, Michels PC, Richter DL, Valois RF, Moore CG. Identification of the factors associated with compliance to therapeutic diets in older adults with end-stage renal disease. Journal of Renal Nutrition 2001;11(2):80-89.

(80) Hollingdale R, Sutton D, Hart K. Facilitating dietary change in renal disease: investigating patients' perspectives. Journal of Renal Care 2008;34(3):136-142.

(81) Burrowes JD, Cockram DB. Achieving patient adherence to diet therapy. In: Kopple JD, Massry SG, editors. Nutritional Management of Renal Disease. 2nd ed. Philadelphia, Pennsylvania: Lippencott Williams & Wilkins; 2003. p. 629.

91

(82) Milas NC, Nowalk MP, Akpele L, Castaldo L, Coyne T, Doroshenko L, et al. Factors associated with adherence to the dietary protein intervention in the Modification of Diet in Renal Disease Study. Journal of the American Dietetic Association 1995;95:1295-1300.

(83) Kuhlmann MK. Management of hyperphosphatemia. Hemodialysis International 2006;10:338-345.

(84) Conway JM, Ingewersen LA, Vinyard BT, Moshfegh AJ. Effectiveness of the US Department of Agriculture 5-step multiple-pass method in assessing food intake in obese and non-obese women. American Journal of Clinical Nutrition 2003;77:1171-1178.

(85) Conway JM, Ingewersen LA, Moshfegh AJ. Accuracy of dietary recall using the USDA five-step multiple-pass method in men: an observational validation study. Journal of the American Dietetic Association 2004;104:595-603.

(86) Health Canada. Canadian Community Health Survey, Cycle 2.2, Nutrition (2004) A Guide to Accessing and Interpreting the Data. 2006.

(87) Bliss RM. Researchers produce innovation in dietary recall. Agricultural Research 2004;June:10-12.

(88) Rhodes DG, Moshfegh AJ, Cleveland LG, Murayi TG, Baer DG, Sebastian RG, et al. Accuracy of 24 hour dietary recalls: preliminary results from USDA AMPM validation study. American Society of Experimental Biology (FASEB) Journal 2004;18(A111).

(89) Blanton CA, Moshfegh AJ, Baer DG, Kretsch MJ. The USDA automated multiple-pass method accurately estimates group total energy and nutrient intake. The Journal of Nutrition 2006;136:2594-2599.

(90) Ard JD, Desmond RA, Allison DB, Conway JM. Dietary restraint and disinhibition do not affect accuracy of 24-hour recall in a multiethnic population. Journal of the American Dietetic Association 2006;106:434-437.

(91) Casey PH, Goolsby SLP, Lensing SY, Perloff BP, Bogle ML. The use of telephone interview methodology to obtain 24-hour dietary recalls. Journal of the American Dietetic Association 1999;99:1406-1411.

(92) National Kidney Foundation I. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Guideline 5: Nutritional Management In Diabetes and Chronic Kidney Disease. 2007.

(93) National Kidney Foundation I. Guideline 12. I. ADULT GUIDELINES, A. MAINTENANCE DIALYSIS 1. Evaluation of Protein-Energy Nutritional Status. 2000; .

(94) Oenning LL, Vogel J, Calvo MS. Accuracy of methods estimating calcium and phosphorus intake in daily diets. Journal of the American Dietetic Association 1988;88:1076-1078.

(95) Sullivan C, Sayre SS, Leon JB, Machekano R, Love TE, Porter D, et al. Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial. Journal of the American Medical Association 2009;301(6):629-635.

(96) Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, et al. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney International 2007;72:1255-1261.

9.0 Appendices Form 1 – St. Michael’s Hospital Consent Form (4 pages)

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Form 2 – Sunnybrook Hospital Consent Form (7 pages)

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Form 3 – Chart Data Collection Form (2 pages)

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Form 4 – Inclusion/Exclusion Form

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Form 5 – 24-hour Dietary Recall (3 pages)

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Form 6 – Processed Food Intake

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Form 7 – Dietary Satisfaction Questionnaire (5 pages)

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Form 8 – Phosphorus Knowledge Test (3 pages)

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Form 9 - Choose/Avoid Handout (2 pages)

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Form 10 – The Phosphorus Point System© Tool (9 pages)

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Form 11 – Phosphorus Point Food Tracker

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Form 12 – Qualitative Data Form

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Form 13 – Phosphorus Additives Handout (2 pages)

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