Chronic kidney disease
Chronic kidney disease.
Position paper 2007
Mai Rosenberg 1, Ruth Kalda 1, Vytautas Kasiulevičius 2 , Aivars
Petersons 3, Margus Lember 1
1 University of Tartu, Estonia
2 University of Vilnius, Lithania
3 Stradins Medical Academy, Riga, Latvia
Table of contents:
Introduction
Chronic kidney disease (CKD) is a worldwide public health
problem that is often under-diagnosed and under-treated.
Definitions and classification
Chronic kidney disease represents a progressive, irreversible
decline in glomerular filtration rate (1). Most chronic
nephropathies unfortunately lack a specific treatment and progress
relentlessly to end stage renal disease. Progressive renal function
loss is a common phenomenon in renal failure irrespectively of the
underlying cause of the kidney disease (2).
In recent years the concept of chronic kidney disease has gained
more attention instead of chronic renal failure which is used to
describe the more advanced stages of CKD. This is especially
important for primary health care where the role of primary care
providers is very important in handling the early phases of CKD to
prevent or postpone chronic renal failure. In the current
literature the terms CKD, renal insufficiency and renal failure are
sometimes used without precisely defining these conditions.
Chronic renal failure indicates to chronically (at least 3
months' duration) reduced kidney function (clearance, glomerular
filtration rate [GFR]). Renal function declines normally with age,
and exact level of decline at a given age that should be considered
pathological is not known.The Kidney Disease Improving Global
Outcomes (KDIGO) statement considers GFR less than 60 mL/minute
pathological at all ages. However, many elderly people have values
less than this (in the USA, about 7% of white people without
diabetes who are aged in their 60s and 15% of those aged in their
70s), and the extent to which low kidney function in the range of
30–60 mL/minute/1.73 m2 is pathological or progressive in all
people is a subject of some controversy. Though people with end
stage renal disease, by definition, have chronic failure of their
kidneys (which may have resulted from an acute or a chronic
process) they are generally not included in the term chronic renal
failure, which in most of the literature and in this chapter refers
exclusively to those with low kidney function who are not treated
with renal replacement therapy.
Chronic kidney disease defined by the Kidney Disease Improving
Global Outcomes (KDIGO) statement as either the presence of
abnormalities in urine or imaging that may lead to progressive
disease or creatinine clearance (or glomerular filtration rate)
less than 60 mL/minute/1.73 m2 . Chronic kidney disease includes
chronic renal failure, but also includes predictors of chronic
renal failure in people with normal kidney function (e.g.
proteinuria), and end stage renal disease.
The National Kidney Foundation - Kidney Disease Outcomes Quality
Initiative (NKF-K/DOQI) workgroup has defined CKD as the following
(10) which have been accepted internationally with some
clarifications (7,11):
· The presence of markers of kidney damage for
OR
· The presence of GFR <60 mL/min/1.73 m2 for 3 months, with
or without other signs of kidney damage as described above.
Based upon representative samples of the United States
population (12), the studies have estimated the prevalence of CKD
in the general population through measurement of markers of kidney
damage, such as elevated serum creatinine concentration, decreased
predicted GFR, and presence of albuminuria. The term “albuminuria”
should be substituted for terms “microalbuminuria” and
“macroalbuminuria”. Increased urinary albumin excretion of albumin
is the earliest manifestation of CKD due to diabetes, other
glomerular diseases and hypertensive nephrosclerosis. Albuminuria
may also accompany tubulointerstitial diaseases, polycysistic
kidney disease, and kidney disease in transplant recipients
(11).
According to the KD:IGO position statement (11) the use of the
term “disease” in CKD is consistent with: 1) the need for action to
improve outcomes through prevention, detection, evaluation and
treatment; 2) providing a message for public, physician and patient
education programs; 3) common usage; and 4) its use in other
conditions defined by findings and laboratory tests, such as
hypertension, diabetes, and hyperlipidemia (11).
Classification of CKD.
CKD classified according to the severity, diagnosis, treatment
and prognosis (11). Suffix “T” is used for all transplant
recipients, at any level of GFR and, “D” for dialysis, for CKD
stage 5 patients treated with dialysis. Clinical evaluation for CKD
should include elucidation of the cause of disease. However, cause
of the disease cannot be ascertained in all cases.
Table
Stage
Description
GFR (mL/min per 1.73 m2)
Related terms
1
Kidney damage with normal or ↑ GFR
≥ 90
Albuminuria
Proteinuria
Hematuria
2
Kidney damage with mild ↓ GFR
60-89
Albuminuria
Proteinuria
Hematuria
“T” if kidney transplant recipient
3
Moderate ↓ GFR
30-59
Chronic renal insufficiencyEarly renal insufficiency
4
Severe ↓ GFR
15-29
Chronic renal insufficiencyLate renal insufficiency
Pre-ESRD
5
Kidney failure
< 15
Renal failure
Uremia
End-stage renal disease
“D” if dialysis (HD, PD)
References
1. Anderson, Brenner
2. Ots M, Pechter U, Tamm A: Characteristics of progressive
renal disease. Clin Chim Acta 2000;2971-2:29-41.
3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global
overview of patients, treatment modalities and development trends.
Nephrol Dial Transplant 2002;1712:2071-2076.
4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal
replacement therapy in developed countries come to an end? Nephrol
Dial Transplant 2007;22:678-680
5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas
of End-Stage Renal Disease in the United States, National
Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD, 2006. Am J Kidney Dis 2006;
47(Suppl 1):S1.
6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M,
Luman M, Ots M, Ritz E: The epidemiology of end-stage renal disease
in the Baltic countries: an evolving picture. Nephrol Dial
Transplant 2001;167:1338-1342.
7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic
kidney disease and screening recommendations. UpToDate 2007; 15
8. http://www.musili.fi/fin/munuaistautirekisteri/
9. K. Kõlvald,…. Renal replacement therapy trends in Estonia.
Transplant Int 2007:
10. K/DOQI clinical practice guidelines for chronic kidney
disease: evaluation, classification, and stratification. Am J
Kidney Dis 2002; 39:S1.),
11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and
classification of chronic kidney disease: A position statement from
Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;
67:2089.
12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular
disease in chronic renal failure. Lancet 2000;3569224:147-152.
13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of
chronic kidney disease and decreased kidney function in the adult
US population: Third National Health and Nutrition Examination
survey. Am J Kidney Dis 2003; 41:1.
14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of
cardiovascular disease in chronic renal disease. Am J Kidney Dis
1998;325 Suppl 3:S112-119.
15. Pereira, BJG. Optimization of pre-ESRD care: The key to
improved dialysis outcomes. Kidney Int 2000; 57:351.
16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr
Opin Nephrol Hypertens 2002;115:483-488.
17. Ritz E, Orth SR: Nephropathy in patients with type 2
diabetes mellitus. N Engl J Med 1999;34115:1127-1133.
18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD:
Renal insufficiency and cardiovascular events in postmenopausal
women with coronary heart disease. J Am Coll Cardiol
2001;383:705-711.
19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak
A, Szabo A, Ritz E: Hyperphosphatemia aggravates cardiac fibrosis
and microvascular disease in experimental uremia. Kidney Int
2003;634:1296-1301.
20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national
epidemic of chronic kidney disease. What we know and what we can
do. Postgrad Med 2001;1103:23-29: quiz 28
21. Meyer KB, Levey AS: Controlling the epidemic of
cardiovascular disease in chronic renal disease: report from the
National Kidney Foundation Task Force on cardiovascular disease. J
Am Soc Nephrol 1998;912 Suppl:S31-42.
22. Holley, JL, Nespor, SL. Nephrologist-directed primary health
care in chronic dialysis patients. Am J Kidney Dis 1993; 21:628
23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists'
practice in health promotion and disease prevention: A survey. Ann
Intern Med 1991; 114:46.
24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC.
Attitudes of Canadian nephrologists, family physicians and patients
with kidney failure toward primary care delivery for chronic
dialysis patients. Nephrol Dial Transplant 2003; 18:305.)
25. Jean L Holley. The nephrologist as primary care physician in
patients with end-stage renal disease. UpToDate 2007; 15
26. Inglismaal tehtud töö NDT, 2007
www.clinicalevidence.org
Epidemiology and causes of CKD
Very few of the causes of chronic renal failure are completely
curable. It is often not necessary to do extensive tests to find a
cause, however, for determining the stage and specific
characteristics of the underlying disese follow-up of patients and
thorough diagnostic work-up is needed. The three major groups of
diseases leading to chronic kidney failure are diabetes,
hypertension and renal diseases (mostly glomerulonephritides,
tubulointerstitial nephritides and hereditary nephropathies, in
particular autosomal dominant polycystic kidney disease ADPKD). In
different countries the proportions of these diseases as a cause of
renal failure are different. However, in the western world the
share of diabetes is steadily increasing.
Out of the advanced or end-stage renal failure (Siegenthaler) in
the UK diabetic nephropathy constitues 19%, hypertension 15%,
chronic glomerulonephrits 10%, chronic tubulointerstitial nephritis
6%, ADPKD 6%.
In the US diabetic nephropathy is the cause of chronic renal
failuer even in 45%, hypertension in 27%, chronic
glomerulonephritis in 11% of cases while chronic tubulointerstitial
nephritis only in 3% and ADPKD in 2%. In Japan chronic
glomerulonephritis is the main reason (47%), diabetic nephropathy
30%, hypertension 10%, chronic tubulointerstitial nephritis 2% and
ADPKD in 2% of cases.
Diabetes is one of the commonest causes of kidney failure in
many countries (3,4,5). However, in Baltic countries diabetes
epidemic has not been yet seen and patients with chronic
glomerulonephritis usually form the main contingent of the
end-stage renal disease (ESRD) population (6). In many countries
there is a rising incidence and prevalence of kidney failure
(3,4,5,6). Although the exact reasons for the growth of the ESRD
patients are unknown, it is postulated that changes in the
demographics of the population, differences in disease burden among
racial groups and under-recognition of earlier stages of CKD and of
risk factors for CKD, may partially explain this growth (7).
However, recent trends show that the rate of increase of new cases
of both diabetic and all-cause ESRD has progressively flattened in
many countries (4,8) but this tendency is not universal and not
seen in other populations (9). However, it is currently impossible
to predict the long-term trend in the incidence rates of RRT in
Europe. Therefore, secondary prevention should be organized as
effective as possible at the population level.
The prevalence and incidence of kidney failure treated by
dialysis and transplantation in the United States have increased
from 1988 to 2004. Whether there have been changes in the
prevalence of earlier stages of chronic kidney disease (CKD) during
this period is uncertain. The prevalence of CKD in the United
States in 1999-2004 is higher than it was in 1988-1994. This
increase is partly explained by the increasing prevalence of
diabetes and hypertension and raises concerns about future
increased incidence of kidney failure and other complications of
CKD. / Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P,
Van Lente F, Levey AS. Prevalence of chronic kidney disease in the
United States. JAMA. 2007;298:2038-47/
The prevalence of CKD in the US adult population was 11% (19.2
million). By stage, an estimated 5.9 million individuals (3.3%) had
stage 1 (persistent albuminuria with a normal GFR), 5.3 million
(3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89
mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59
mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15
to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage
5, or kidney failure. Aside from hypertension and diabetes, age is
a key predictor of CKD, and 11% of individuals older than 65 years
without hypertension or diabetes had stage 3 or worse CKD. / Coresh
J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic
kidney disease and decreased kidney function in the adult US
population: Third National Health and Nutrition Examination Survey.
Am J Kidney Dis. 2003;41:1-12./
References:
Siegenthaler W. Differential diagnosis in internal medicine.
Thieme. Stuttgart New York 2007
1. Anderson, Brenner
2. Ots M, Pechter U, Tamm A: Characteristics of progressive
renal disease. Clin Chim Acta 2000;2971-2:29-41.
3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global
overview of patients, treatment modalities and development trends.
Nephrol Dial Transplant 2002;1712:2071-2076.
4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal
replacement therapy in developed countries come to an end? Nephrol
Dial Transplant 2007;22:678-680
5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas
of End-Stage Renal Disease in the United States, National
Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD, 2006. Am J Kidney Dis 2006;
47(Suppl 1):S1.
6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M,
Luman M, Ots M, Ritz E: The epidemiology of end-stage renal disease
in the Baltic countries: an evolving picture. Nephrol Dial
Transplant 2001;167:1338-1342.
7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic
kidney disease and screening recommendations. UpToDate 2007; 15
8. http://www.musili.fi/fin/munuaistautirekisteri/
9. K. Kõlvald,…. Renal replacement therapy trends in Estonia.
Transplant Int 2007:
10. K/DOQI clinical practice guidelines for chronic kidney
disease: evaluation, classification, and stratification. Am J
Kidney Dis 2002; 39:S1.),
11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and
classification of chronic kidney disease: A position statement from
Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;
67:2089.
12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular
disease in chronic renal failure. Lancet 2000;3569224:147-152.
13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of
chronic kidney disease and decreased kidney function in the adult
US population: Third National Health and Nutrition Examination
survey. Am J Kidney Dis 2003; 41:1.
14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of
cardiovascular disease in chronic renal disease. Am J Kidney Dis
1998;325 Suppl 3:S112-119.
15. Pereira, BJG. Optimization of pre-ESRD care: The key to
improved dialysis outcomes. Kidney Int 2000; 57:351.
16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr
Opin Nephrol Hypertens 2002;115:483-488.
17. Ritz E, Orth SR: Nephropathy in patients with type 2
diabetes mellitus. N Engl J Med 1999;34115:1127-1133.
18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD:
Renal insufficiency and cardiovascular events in postmenopausal
women with coronary heart disease. J Am Coll Cardiol
2001;383:705-711.
19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak
A, Szabo A, Ritz E: Hyperphosphatemia aggravates cardiac fibrosis
and microvascular disease in experimental uremia. Kidney Int
2003;634:1296-1301.
20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national
epidemic of chronic kidney disease. What we know and what we can
do. Postgrad Med 2001;1103:23-29: quiz 28
21. Meyer KB, Levey AS: Controlling the epidemic of
cardiovascular disease in chronic renal disease: report from the
National Kidney Foundation Task Force on cardiovascular disease. J
Am Soc Nephrol 1998;912 Suppl:S31-42.
22. Holley, JL, Nespor, SL. Nephrologist-directed primary health
care in chronic dialysis patients. Am J Kidney Dis 1993; 21:628
23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists'
practice in health promotion and disease prevention: A survey. Ann
Intern Med 1991; 114:46.
24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC.
Attitudes of Canadian nephrologists, family physicians and patients
with kidney failure toward primary care delivery for chronic
dialysis patients. Nephrol Dial Transplant 2003; 18:305.)
25. Jean L Holley. The nephrologist as primary care physician in
patients with end-stage renal disease. UpToDate 2007; 15
26. Inglismaal tehtud töö NDT, 2007
Screening
Early treatment of chronic kidney disease and its complications
may delay or prevent the development of end-stage renal disease,
therefore detection of chronic kidney disease is believed to be a
priority for primary care. (Snyder S, Pendergraph B 2005) There are
reports suggesting that chronic kidney disease often is not
detected, even when patients have access to primary care. (National
Kidney Foundation. 2003; McClellan WM et al 2003)
Which patients to screen? There is overwhelming consensus that
screening for chronic renal disease should include high-risk
groups. These include patients who have a family history of the
disese, patients who have diabetes, hypertension, recurrent urinary
tract infections, urinary obstruction or a systemic illness that
affects the kidneys (National Kidney Foundation. 2002). Screening
for asymptomatic persons beyond the above-mentioned patient groups
has not found justification. The only exception are pregnant women:
screening for bacteriuria is justified and its effect proven as the
treatment of asymptomatic bacteriuria has been found to be
effective in benefit of newborns /US Task Force..../
How to screen? The most widely used methods for screening for
kidney disease are an analysis of a random urine sample for
albuminuria and a serum creatinine measurement to calculate an
estimated glomerular filtration rate (GFR). It is recommendable to
use both of these methods as significant kidney disease can present
with diminished GFR or proteinuria, or both. (Garg AX et al
2002)
GFR is an indication of functioning kidney mass, the stages of
chronic renal failure are based on an estimated GFR:
Stage 1 GFR (ml per min per 1.73 m²) >89
Stage 2 60-89
Stage 3 30-59
Stage 4 15-29
Stage 5 <15 or dialysis
Significant kidney dysfunction may be present despite a normal
serum creatinine level. An estimated GFR based on serum creatinine
level correlates better with direct measures of the GFR and detects
more cases of chronic kidney disease than does the serum creatinine
level alone.
Clinically useful GFR estimates are calculated from the measured
serum creatinine level after ajustments for age, sex and race.
(Levey AS et al 1999; Cockcroft DW, Gault MH 1976) The two most
commonly used formulas for GFR estimation are the MDRD
(Modification of Diet in Renal Sisease) study equation and the
Cockcroft-Gault equation. Validation studies in middle-aged
patients with chronic kidney disease showed MDRD study equation to
be more accurate. (Levey AS et al 1999). However, the MDRD study
equation was found to systematically underestimate the GFR in
patients without chronic kidney disease.( Rule AD et al 2004)
FORMULAS:
Abbreviated MDRD study equation12†
GFR (mL per minute per 1.73 m2) = 186 X (SCr)-1.154 X
(age)-0.203 X (0.742, if female) X (1.210, if black)
Cockcroft-Gault equation13
CCr (mL per minute) =
(140 - age) X weight
X (0.85, if female)
72 X SCr
GFR = glomerular filtration rate; MDRD = Modification of Diet in
Renal Disease; SCr = serum creatinine concentration; CCr =
creatinine clearance.
*-For each equation, SCr is in milligrams per deciliter, age is
in years, and weight is in kilograms.
†-In validation studies,14-17 the MDRD study equation performed
as well as versions with more variables; however, a recent study18
found that the equation underestimated the GFR in patients who did
not have chronic kidney disease.
CCr (mL per minute) =(140 - age) X weight X (0.85, if
female)
0,81 X SCr
SCr Micromol/L
In most situations and as long as kidney function is stable, a
calculated GFR can replace measurement of a 24-hour urine
collection for creatinine clearance. Determination of creatinine
clearance using 24-hour urine collection is still required in
pregnant women, patients with extremes of age and weight, patients
with malnutrition, patients with skeletal muscle diseases,
paraplegia or quadripülegia, patients with a vegetarian diet and
rapidly changuing kidney function. (Snyder S, Pendergraph B
2005)
Detecting and quantitation of proteinuria are essential to the
diagnosis and treatment of chronic kidney disease. Albumin, the
predominant protein excreted by the kidney in most types of renal
diseases, can be detected by urine dipstick testing. The
protein-creatinine ratio in an early-morning random urine sample
correlates well with 24-hour urine protein excretion and is much
easier to obtain. (National Kidney Foundation 2002).
Microalbuminuria often heralds the onset of diabetic nephropathy,
therefore screening for microalbuminuria is recommended for all
patients at risk for kidney disese. Screening can be performed
using a microalbumin-sensitive dipstick or analysis of a random
morning urine sample to determine the microalbumin-creatinine
ratio.
Screening for the diseases that may lead to chronic kidney
failure. The most important reasons of chronic renal failure are
diabetes and hypertension. Therefore early detection of these
diseases and appropriate treatment is a method of avoiding or
postponing complications, incl. chronic kidney failure. However,
population-based screening for diabetes has not been found as an
effective approache for improving diabetes outcomes. Screening of
hypertension by measurement of blood pressure at the office visits
has found support in many guidelines.
Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria
and renal insufficiency prevalence guides population screening:
results from the NHANES III. Kidney Int 2002; 61:2165-75
Snyder S, Pendergraph B. Detection and evaluation of chronic
kidney disease. Am Fam Physician 2005;72:1723-34
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more
accurate method to estimate glomerular filtration rate from serum
creatinine: a new prediction equation. Modification of Diet in
Renal Disease Study Group. Ann Intern Med 1999; 130:461-70.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from
serum creatinine. Nephron 1976; 16:31-41
National Kidney Foundation. KEEP: Kidney Early Evaluation
Program. Annual data report. Program introduction. Am J Kidney Dis
2003; 42(5 suppl 4): S5-15;
McClellan WM, Ramirez SP, Jurkovitz C. Screening for chronic
kidney disease: unresolved issues. J Am Soc Nephrol 2003; 14 (7
suppl 2):S81-7.
Rule AD, Larson TS, Bergstrahl EJ, Slezak JM, Jacobsen SJ, Cosio
FG. Using serum creatinine to estimate glomerular filtration rate:
accuracy in good health and in chronic kidney disease. Ann Intern
Med 2004; 141:929-37
National Kidney Foundation. K/DOQI, clinical practice guidelines
for chronic kidney disease: evaluation, classification and
stratification. Am J Kidney Dis 2002; 39 (2 suppl 1): S1-266.
US Task Force….
Prevention
Main part of the total medical cost budget involves the
treatment of CVD. Primary and secondary prevention of
cardiovascular and kidney disease remain the main purpose in modern
medicine as cardiovascular morality represents the main reason of
death in the world. The main cause of death in patients with CKD is
cardiovascular catastrophe and the risk to die is in ESRD patients
even 10-20 times higher compared with general population (13,14).
Despite the magnitude of the resources committed to the treatment
of ESRD and the substantial improvements in the quality of dialysis
therapy, these patients continue to experience significant
mortality and morbidity, and a reduced quality of life. Therefore,
CKD should be recognized as early as possible and all prevention
interventions that may arrest the kidney disease progression should
be used. Earlier stages of CKD can be detected through laboratory
testing, and that therapeutic interventions implemented early in
the course of CKD
are effective in slowing or preventing the progression toward
kidney failure and its associated complications (15).
When kidney disease progresses CKD patients become hypertensive,
have acquired combined hyperlipidemia and hyperhomocysteinemia,
increased oxidative stress, and decreased physical activity and
psychosocial stress. If patients choose to smoke, the additive risk
is profound (16). Diabetes mellitus is a major risk factor for both
cardiovascular disease and CKD progression (17). Moreover, CKD
patients are becoming older and are often menopausal if female
(18). Finally, renal patients have a dramatic tendency for vascular
and cardiac calcification that is related with hyperphosphatemia
and secondary hyperparathyroidism (19). Also, the risk of
atherosclerotic cardiovascular diseases (CVD) in patients with CRF,
especially in patients on renal replacement therapy, has shown to
be 10-20 times greater than in the general population (14, 20).
The management of several renal and CVD risk factors as
hypertension, overweight, hypercholesterolemia,
hypertriglyceridemia, and others should begin early in the course
of chronic renal insufficiency with reno- and vasoprotective
medications (21). In addition to classical risk factors such as
age, male gender, smoking, hypertension, diabetes and dyslipidemia,
physical inactivity, which also exist in the general population,
patients with chronic renal failure have specific risk factors.
Additional specific risk factors for advanced CKD are various
uraemic toxines, hyperphosphatemia, severe prolonged oxidative
stress, malnutrition, and hyperuricemia and immunosupressive
treatment. Psychosocial factors, such as environmental stress and
responsiveness to stress should not be unmentioned. The approach to
the risk factors should be guided by the principle that chronic
renal disease patients belong into the highest risk group for
subsequent atherosclerotic complications.
References
1. Anderson, Brenner
2. Ots M, Pechter U, Tamm A: Characteristics of progressive
renal disease. Clin Chim Acta 2000;2971-2:29-41.
3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global
overview of patients, treatment modalities and development trends.
Nephrol Dial Transplant 2002;1712:2071-2076.
4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal
replacement therapy in developed countries come to an end? Nephrol
Dial Transplant 2007;22:678-680
5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas
of End-Stage Renal Disease in the United States, National
Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD, 2006. Am J Kidney Dis 2006;
47(Suppl 1):S1.
6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M,
Luman M, Ots M, Ritz E: The epidemiology of end-stage renal disease
in the Baltic countries: an evolving picture. Nephrol Dial
Transplant 2001;167:1338-1342.
7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic
kidney disease and screening recommendations. UpToDate 2007; 15
8. http://www.musili.fi/fin/munuaistautirekisteri/
9. K. Kõlvald,…. Renal replacement therapy trends in Estonia.
Transplant Int 2007:
10. K/DOQI clinical practice guidelines for chronic kidney
disease: evaluation, classification, and stratification. Am J
Kidney Dis 2002; 39:S1.),
11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and
classification of chronic kidney disease: A position statement from
Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;
67:2089.
12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular
disease in chronic renal failure. Lancet 2000;3569224:147-152.
13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of
chronic kidney disease and decreased kidney function in the adult
US population: Third National Health and Nutrition Examination
survey. Am J Kidney Dis 2003; 41:1.
14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of
cardiovascular disease in chronic renal disease. Am J Kidney Dis
1998;325 Suppl 3:S112-119.
15. Pereira, BJG. Optimization of pre-ESRD care: The key to
improved dialysis outcomes. Kidney Int 2000; 57:351.
16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr
Opin Nephrol Hypertens 2002;115:483-488.
17. Ritz E, Orth SR: Nephropathy in patients with type 2
diabetes mellitus. N Engl J Med 1999;34115:1127-1133.
18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD:
Renal insufficiency and cardiovascular events in postmenopausal
women with coronary heart disease. J Am Coll Cardiol
2001;383:705-711.
19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak
A, Szabo A, Ritz E: Hyperphosphatemia aggravates cardiac fibrosis
and microvascular disease in experimental uremia. Kidney Int
2003;634:1296-1301.
20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national
epidemic of chronic kidney disease. What we know and what we can
do. Postgrad Med 2001;1103:23-29: quiz 28
21. Meyer KB, Levey AS: Controlling the epidemic of
cardiovascular disease in chronic renal disease: report from the
National Kidney Foundation Task Force on cardiovascular disease. J
Am Soc Nephrol 1998;912 Suppl:S31-42.
22. Holley, JL, Nespor, SL. Nephrologist-directed primary health
care in chronic dialysis patients. Am J Kidney Dis 1993; 21:628
23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists'
practice in health promotion and disease prevention: A survey. Ann
Intern Med 1991; 114:46.
24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC.
Attitudes of Canadian nephrologists, family physicians and patients
with kidney failure toward primary care delivery for chronic
dialysis patients. Nephrol Dial Transplant 2003; 18:305.)
25. Jean L Holley. The nephrologist as primary care physician in
patients with end-stage renal disease. UpToDate 2007; 15
26. Inglismaal tehtud töö NDT, 2007
Predialysis
Renal replacement therapy- role of primary care , internists and
nephrologists
Availability of renal replacement therapy (RRT) forces the
nephrologist to consider its application in every patient in whom
it might be indicated. As kidney disease progresses patients cannot
get help from family physician because of predialysis activities
and preparations to RRT. Patients can feel even that the
nephrologist is the only doctor who should manage all medical
problems. Ideally, RRT is planned early and each patient and
clinical setting judged individually. Usually, specific predialysis
program takes several months and during this time CKD patients
often visit dialysis center.
There are many clinical problems in patients with CKD during
predialysis and RRT period that can be associated with CKD but not
always. Therefore, nephrologists often provide primary care or
nonrenal related medical care to predialysis or to patients
undergoing chronic haemodialysis because patient visits the center
often. The nephrologist is the first who makes diagnose for
instance of acute illness. Evidence shows that many patients do not
have even family physician and patients often feel also that the
nephrologist should manage their acute illness. On the other hand,
comparison of HD and CAPD patients PD patients less depended upon
their nephrologists (22).
A paucity of objective data exists concerning the nephrologist's
role as a primary care provider. Several studies suggest that the
volume and type of practice provided by the nephrologist for
patients with ESRD may be similar to that of the primary care
practitioner (23,24,25). The problem is that if CKD patient numbers
increases then in many places may be lack of nephrologists who have
time and also experience to manage all medical problems in their
RRT patients. It is probably true that patient outcome may be
influenced by the expertise of the physician but no studies have
been focused on the topic to compare outcome data of CKD
populations managed only with specialist and both with specialist
together with internist
References
1. Anderson, Brenner
2. Ots M, Pechter U, Tamm A: Characteristics of progressive
renal disease. Clin Chim Acta 2000;2971-2:29-41.
3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global
overview of patients, treatment modalities and development trends.
Nephrol Dial Transplant 2002;1712:2071-2076.
4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal
replacement therapy in developed countries come to an end? Nephrol
Dial Transplant 2007;22:678-680
5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas
of End-Stage Renal Disease in the United States, National
Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD, 2006. Am J Kidney Dis 2006;
47(Suppl 1):S1.
6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M,
Luman M, Ots M, Ritz E: The epidemiology of end-stage renal disease
in the Baltic countries: an evolving picture. Nephrol Dial
Transplant 2001;167:1338-1342.
7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic
kidney disease and screening recommendations. UpToDate 2007; 15
8. http://www.musili.fi/fin/munuaistautirekisteri/
9. K. Kõlvald,…. Renal replacement therapy trends in Estonia.
Transplant Int 2007:
10. K/DOQI clinical practice guidelines for chronic kidney
disease: evaluation, classification, and stratification. Am J
Kidney Dis 2002; 39:S1.),
11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and
classification of chronic kidney disease: A position statement from
Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;
67:2089.
12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular
disease in chronic renal failure. Lancet 2000;3569224:147-152.
13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of
chronic kidney disease and decreased kidney function in the adult
US population: Third National Health and Nutrition Examination
survey. Am J Kidney Dis 2003; 41:1.
14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of
cardiovascular disease in chronic renal disease. Am J Kidney Dis
1998;325 Suppl 3:S112-119.
15. Pereira, BJG. Optimization of pre-ESRD care: The key to
improved dialysis outcomes. Kidney Int 2000; 57:351.
16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr
Opin Nephrol Hypertens 2002;115:483-488.
17. Ritz E, Orth SR: Nephropathy in patients with type 2
diabetes mellitus. N Engl J Med 1999;34115:1127-1133.
18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD:
Renal insufficiency and cardiovascular events in postmenopausal
women with coronary heart disease. J Am Coll Cardiol
2001;383:705-711.
19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak
A, Szabo A, Ritz E: Hyperphosphatemia aggravates cardiac fibrosis
and microvascular disease in experimental uremia. Kidney Int
2003;634:1296-1301.
20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national
epidemic of chronic kidney disease. What we know and what we can
do. Postgrad Med 2001;1103:23-29: quiz 28
21. Meyer KB, Levey AS: Controlling the epidemic of
cardiovascular disease in chronic renal disease: report from the
National Kidney Foundation Task Force on cardiovascular disease. J
Am Soc Nephrol 1998;912 Suppl:S31-42.
22. Holley, JL, Nespor, SL. Nephrologist-directed primary health
care in chronic dialysis patients. Am J Kidney Dis 1993; 21:628
23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists'
practice in health promotion and disease prevention: A survey. Ann
Intern Med 1991; 114:46.
24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC.
Attitudes of Canadian nephrologists, family physicians and patients
with kidney failure toward primary care delivery for chronic
dialysis patients. Nephrol Dial Transplant 2003; 18:305.)
25. Jean L Holley. The nephrologist as primary care physician in
patients with end-stage renal disease. UpToDate 2007; 15
26. Inglismaal tehtud töö NDT, 2007
Concomitant major health problems in CKD patients (infections,
nutrition, anaemia)
Infection
The more common pathogenic viral infections in chronic kidney
disease (CKD) are cytomegalovirus, HIV-1, hepatitis C virus and
parvovirus B19. Infectious diseases are the second most common
cause of death in end-stage renal disease (ESRD) patients.
(1,2)
Among a representative sample of the US population, hepatitis C
is independently associated with albuminuria among adults over the
age of 40; however, it does not seem to be significantly associated
with a low eGFR in this population-based cross-sectional analysis.
(3) Hepatitis C also is a complicating factor among patients with
end-stage renal disease and renal transplants. The source of HCV
infection in these patients can be nosocomial. Screening and
careful attention to infection control precautions are mandatory
for dialysis units to prevent the spread of hepatitis C (12).
Infection with parvovirus B19 causes several clinical syndromes
(fifth disease, transient aplastic crisis, pure red cell aplasia,
and hydrops fetalis) and may contribute to other illnesses. (4)
Human immunodeficiency virus (HIV)-infected patients can develop
different types of chronic kidney disease (CKD). The most common
histological finding of renal biopsy is HIV-associated nephropathy
(HIVAN). HIVAN is now the third most common cause of end stage
renal failure (ESRF) (after diabetes mellitus and hypertension) in
African-Americans aged 20–64 years. With the improved survival
after the use of highly active antiretroviral therapy (HAART) in
HIV-infected patients, there are increasing reports of development
of CKD and ESRF in this population. (5) All patients at the time of
human immunodeficiency virus (HIV) diagnosis should be assessed for
existing kidney disease with a screening urine analysis for
proteinuria and a calculated estimate of renal function. Additional
evaluations (including quantification of proteinuria, renal
ultrasound, and potentially renal biopsy) and referral to a
nephrologist are recommended for patients with proteinuria of grade
>1+ by dipstick analysis or glomerular filtration rate (GFR)
<60 mL/min per 1.73 m2 (6)
Regardless of age and the presence of other comorbid illnesses,
it is recommended that patients with chronic kidney disease receive
regular vaccination. Hepatitis B is one of the most serious
infectious diseases in the world. The virus can be transmitted
among high-risk groups including CKD patients. HBV vaccination in
patients with kidney disease remains highly recommendable.
Hepatitis A virus vaccination among the general population has been
used for decades. HAV vaccination in ESRD patients is well
tolerated and immunogenic. Varicella may be severe and fatal
infection in immunocompromised ESRD children. Varicella vaccination
is safe and effective in ESRD patients and is thus recommended in
these patients. Influenza is a common infection among CKD patients.
Several studies showed that influenza vaccination was safe and
effective in patients with CKD despite an impaired antibody
response. In conclusion, influenza vaccination is highly
recommended among ESRD patients. ESRD patients should thus receive
Haemophilus influenza type B vaccine at the same doses as for
healthy subjects. All children should be treated with measles,
mumps and rubella vaccines (MMR), including dialysis patients.
Diphtheria and tetanus infections can be prevented by using
vaccines in ESRD patients. Pneumococcal vaccination is thus
recommended in CKD patients with standard doses of 23-valent
pneumococcal polysaccharide vaccine, but revaccination should be
performed within 3–5 years. Live vaccines (yellow fever, polio,
varicella and MMR vaccines) are generally avoided because they
present a theoretical risk of vaccine-induced infection. (7)
Infection after transplantation
Infections remain the second most common cause of death in
kidney transplant recipients. The risk for infection in these
patients is determined primarily by the intensity of exposure to
potential pathogens and the net state of immunosuppression. (8)
Overall, the most prevalent opportunistic infections are viral, and
CMV is the primary virus involved. CMV is the most common viral
infection in the transplant population. CMV causes 2 major types of
problems: direct effects, such as CMV syndrome and tissue invasive
disease; and indirect effects, such as acute and chronic rejection,
super-infections, cardiac complications, diabetes, and lymphoma.
CMV infection and disease have been reported to be independent risk
factors for acute renal allograft rejection. (9) Drugs that prevent
CMV, either valacyclovir (10) or ganciclovir (11) or both, decrease
the incidence of acute rejection. However, a host of
community-acquired and opportunistic bacterial, viral, and fungal
infections may occur at different rates depending on the period
after transplantation. To reduce the burden of infection-related
morbidity and mortality, patient vaccination status should be
reviewed at the first clinic visit, and a vaccination strategy
should be developed, keeping in mind that live vaccines are not
given after transplantation and that patients, close contacts, and
family members should receive injectable influenza vaccine yearly
(inhaled influenza vaccine should not be given to transplant
recipients or family members). Pneumococcal polysaccharide vaccine
should be administered before transplantation and repeated every 3
to 5 yr after initial vaccination. Vaccination series should be
restarted approximately 6 mo after transplantation, and efficacy
should be documented by serologic assays when available. Finally,
adult travelers after kidney transplantation need appropriate
counseling and vaccinations before their tri). (8)
References:
1. LeslieA.Bruggeman // Viral Subversion Mechanisms in Chronic
Kidney Disease Pathogenesis // Clin. J. Am. Soc. Nephrol., Jul
2007; 2: S13 - S19.
2. Foley RN. // Infections in patients with chronic kidney
disease // Infect Dis Clin North Am. 2007 Sep;21(3):659-72.
3. Judith I. Tsui, Eric Vittinghoff, Michael G. Shlipak, and Ann
M. O’Hare // Relationship between Hepatitis C and Chronic Kidney
Disease: Results from the Third National Health and Nutrition
Examination Survey // J. Am. Soc. Nephrol., Apr 2006; 17: 1168 -
1174.
4. Meryl Waldman and Jeffrey B. Kopp // Parvovirus B19 and the
Kidney // Clin. J. Am. Soc. Nephrol., Jul 2007; 2: S47 - S56.
5. Chi Yuen Cheung, Kim Ming Wong, Man Po Lee, Yan Lun Liu,
Heidi Kwok, Rita Chung, Ka Foon Chau, Chung Ki Li, and Chun Sang Li
// Prevalence of chronic kidney disease in Chinese HIV-infected
patients // Nephrol. Dial. Transplant., Nov 2007; 22: 3186 -
3190.
6. Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS,
Rodriguez RA, Tashima KT, Roland M, Franceschini N, Palella FJ,
Lennox JL, Klotman PE, Nachman SA, Hall SD, Szczech LA. Guidelines
for the management of chronic kidney disease in HIV-infected
patients: recommendations of the HIV Medicine Association of the
Infectious Diseases Society of America. Clin Infect Dis 2005
Jun 1;40(11):1559-85.
7. Nicolas Janus, Launay-Vincent Vacher, Svetlana Karie, Elena
Ledneva, and Gilbert Deray // Vaccination and Chronic Kidney
Disease// Nephrol. Dial. Transplant., Dec 2007;
10.1093/ndt/gfm851.
8. Arjang Djamali, Millie Samaniego, Brenda Muth, Rebecca
Muehrer, R. Michael Hofmann, John Pirsch, Andrew Howard, Georges
Mourad, and Bryan N. Becker // Medical Care of Kidney Transplant
Recipients after the First Posttransplant Year // Clin. J. Am. Soc.
Nephrol., Jul 2006; 1: 623 - 640.
9. Sageda S, Nordal KP, Hartmann A, et al. The impact of
cytomegalovirus infection and disease on rejection episodes in
renal allograft recipients. Am J Transplant. 2002;2:850-856.
10. Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for
the prevention of cytomegalovirus disease after renal
transplantation. N Engl J Med. 1999;340:1462-1470.
11. Ricart MJ, Malaise J, Moreno A, Crespo M, Fernandez-Cruz L.
Cytomegalovirus: occurrence, severity, and effect on graft survival
in simultaneous pancreas-kidney transplantation. Nephrol Dial
Transplant. 2005;20(suppl 2):ii25-ii32, ii62.
12. CM Meyers, LB Seeff, CO Stehman-Breen // Hepatitis C and
renal disease: an update. // Am J Kidney Dis. 2003
Oct;42(4):631-57
Nutrition
Dietary recommendation is important in management of CKD and the
maintenance of broader health in CKD patients. Malnutrition is a
frequent finding in ESRF, affecting 30-40% of patients. About 10%
of patients on maintenance dialysis show signs of severe
malnutrition. (1). Family physicians will be mostly efficient at
the stage of malnutrition prevention, by implementing an early,
interactive dietary and nutritional care programs in close
collaboration with specialized dietitians.
Extensive European (2,3) and US (4,11) guidelines on the
assessment of nutrition in renal patients are available. All
patients with stage 4-5 CKD should undergo regular nutritional
screening. Nutritional assessment should include a minimum of a
record of body weight prior to onset of ill health (well weight),
current body weight and ideal body weight; body mass index
(weight/height2); subjective global assessment, based on either a
3- or 7-point scale. Other measures of nutritional state are: serum
creatinine, serum lipids, serum albumin and handgrip strength. If a
patient has GFR < 30 ml/min per 1.73 m2, then his/her
nutritional status should be monitored by measuring body weight and
serum albumin every three months. (9) There is no single ‘gold
standard’ measure of nutritional state. Therefore a panel of
measurements should be used, reflecting the various aspects of
protein-calorie nutrition.
The dietary recommendations are different in all countries, but
all guidelines agree that the energy intake in CKD patients is 35
kcal/kg/day and 30 kcal/kg/day may be sufficient in those over
the age of 60. Sodium, total fat, cholesterol, carbohydrate,
protein, phosphorus, potassium are restricted for CKD patients (1
table).
Table 1. Macronutrient Composition and Mineral Content of the
Dietary Approaches to Stop Hypertension (DASH) Diet Recommended by
JNC 7, with Modification for Stages 3–4 of CKD (11)
Nutrient
Stage 1 – 2 of CKD
Stage 3 – 4 of CKD
Sodium (g/d)*
< 2,4
< 2,4
Total fat (% of calories)
< 30
< 30
Saturated fat (% of calories)
< 10
< 10
Cholesterol (mg/d)
< 200
< 200
Carbohydrate (% of calories)**
50 – 60
50 – 60
Protein (g/kg/d, % of calories)
1,4 (18)
0,6 – 0,8 (10)
Phosphorus (g/d)
1,7
0,8 – 1,0
Potassium (g/d)
>4
2 - 4
*Not recommended for patients with “salt-wasting”
**Adjust so total calories from protein, fat and carbohydrate is
100 %
The effects of dietary protein restriction are controversial. A
meta-analysis in 1996 concluded that this intervention reduces
proteinuria and slows the rate of the progression by reducing the
rate of decline of GFR.(5) A later meta-analysis concluded that
effects were less in RCTs than in non-RCT studies, that the effect
was relatively greater in patients with diabetes, and that the
magnitude of the effect was relatively weak. A Cochrane review,
last updated in 1997 and not confined to RCTs, concluded that
reducing protein intake does appear to slow progression of
nephropathy in type 1 diabetes, but identified several unanswered
questions: the level of protein restriction that should be used,
whether compliance could be expected in routine care, and whether
improvement in intermediate outcomes (eg creatinine clearance)
would translate into improved clinical outcomes.(6) Since those
reports an RCT confined to patients with type 2 diabetes and
nephropathy has reported negative effects,(7) but an RCT in type 1
patients suggested a reduction in mortality.(8)
Accordingly, the K/DOQI guidelines have recommended that CKD
patients (GFR < 25 ml/min) receive a diet providing 0.6 g/kg of
desirable body weight (DBW) per day of proteins (11), while others
suggest that the protein content of the diet should not be lower
than 0.75 g/kg/day, and should not exceed 0.8–1.0 g/kg/day (12–16).
Diets with <0.55 g/kg/day of proteins are strongly discouraged,
for the risk of protein malnutrition (17). Some studies advocate
that the reduction in protein intake below 0.8 g/kg/day in patients
with advanced renal failure should be considered a criterion for
starting dialysis therapy (16).
Data of the last good quality study suggest that the 0.55 g/day
diet guarantees a better metabolic control, as mirrored by the less
frequent use of drugs, and it is not associated with a risk of
malnutrition. (17)
1. D Fouque and F Guebre-Egziabher // An update on nutrition in
chronic kidney disease. // Int Urol Nephrol, January 1, 2007;
39(1): 239-46.
2. Clinical Practice Guidelines for the Care of Patients with
Chronic Kidney Disease // UK Renal Association Clinical Practice
Gudelines 4th Edition 2007 //www.renal.org/guidelines
3. Denis Fouque, Marianne Vennegoor, Piet Ter Wee // EBPG
Guideline on Nutrition // Nephrol. Dial. Transplant., May 2007; 22:
ii45 - ii87.
4. American Dietetic Association. Chronic kidney disease
(non-dialysis) medical nutrition therapy protocol. Chicago (IL):
American Dietetic Association; 2002 May.
5. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect
of dietary protein restriction on the progression of diabetic and
nondiabetic renal diseases: a meta-analysis. Ann Intern Med
1996;124: 627–32.
6. Waugh NR, Robertson AM. Protein restriction for diabetic
renal disease. Cochrane Database Syst Rev 2000;(2):CD002181.
7. Pijls LT, de Vries H, van Eijk JT, Donker AJ. Protein
restriction, glomerular filtration rate and albuminuria in patients
with type 2 diabetes mellitus: a randomized trial. Eur J Clin Nutr
2002;56:1200–7.
8. Hansen HP, Tauber-Lassen E, Jensen BR, Parving HH. Effect of
dietary protein restriction on prognosis in patients with diabetic
nephropathy. Kidney Int 2002;62:220–8.
9. W. Kline Bolton // Renal Physicians Association Clinical
Practice Guideline: Appropriate Patient Preparation For Renal
Replacement Therapy: Guideline Number 3 // J Am Soc Nephrology, 14:
1406–1410, 2003
10. Chronic Kidney Disease 2006: A Guide to Select NKF-KDOQI
Gudelines and Recommendation
www.kidney.org/professionals/kls/pdf/Pharmacist_CPG.pdf
11. National Kidney Foundation. K/DOQI Clinical Practice
Guidelines for nutrition in chronic renal failure. Am J Kidney Dis
(2000) 35:S56–S57.
12. CARI. Caring for Australian with Kidney Impairment. In:
Chronic Kidney Disease. Nutrition and Growth in Kidney Disease
Guidelines.
http://www.cari.org.au/ckd_nutrition_list_updating.php.
13. Prichard S. Clinical Practice Guidelines of the Canadian
Society of Nephrology for the treatment of patients with chronic
renal failure: a re-examination. Contrib Nephrol (2003)
140:163–169.
14. Cianciaruso B, Barsotti G, Oldrizzi L, Gentile MG, Del
Vecchio L. Italian Society of Nephrology. Conservative therapy
Guidelines for chronic renal failure. G Ital Nefrol (2003) 20(Suppl
24):48–60.
15. The UK CKD Guidelines (2005) on the Renal Association
website: http://www.renal.org/CKDguide/ckd.html.
16. Churchill DN, Blake PG, Jindal KK, Toffelmire EB, Goldstein
MB. Guidelines for Treating Patients with CRF. Chapter 1: Clinical
Practice Guidelines for Initiation of Dalysis. J Am Soc Nephrol
(1999) 10:S287–S321.
17. Bruno Cianciaruso, Andrea Pota, Antonio Pisani, Serena
Torraca, Roberta Annecchini, Patrizia Lombardi, Alfredo Capuano,
Paola Nazzaro, Vincenzo Bellizzi, and Massimo Sabbatini //
Metabolic effects of two low protein diets in chronic kidney
disease stage 4–5—a randomized controlled trial //Nephrol. Dial.
Transplant., doi:10.1093/ndt/gfm576
Anaemia
Anemia is an early and common complication of chronic kidney
disease. (1) The prevalence of anemia varies with the degree of
renal impairment in predialysis patients with CKD, but once
end-stage kidney failure occurs, all patients are eventually
affected. In the NHANES III (the Third National Health and
Nutrition Examination Survey) study (2), only 1% of participants
with a glomerular filtration rate (GFR) > 60 ml/min were found
to suffer from anaemia [as defined in this study as a haemoglobin
(Hb) concentration <12 g/dl in men or <11 g/dl in women].
However, in a cohort of patients with CKD, 25% of patients with a
GFR >50 ml/min had Hb <12 g/dl (2). CKD patient categories
with diabetes mellitus, congestive heart failure, diseases e.g.
vasculitis, lupus erythematosus, advanced age, kidney
transplantation are at high risk for anaemia development and should
receive a greater level of attention. (3)
According representative meta-analysis compared with Hb values
of >130 g/L or more in the CKD population with cardiovascular
disease, Hb values of <120 g/L were associated with lower
all-cause mortality. Hb values of 100 g/L or less reduced the risk
of hypertension, but increased the risk of seizures. From the
available trial evidence, in CKD patients with cardiovascular
disease, the benefits associated with higher Hb targets (reduced
seizures) are outweighed by the harms (increased risk of
hypertension and death). (4) Because anaemia is an early
complication of CKD, patients with a GFR <60 ml/min/1.73 m2
should have their Hb level checked, and if found to be low then
their anaemia should be further investigated and treated, as
recommended by international guidelines (European Best Practice
Guidelines (EBPG) or K/DOQI clinical practice guidelines)
(5,7).
Family physician role in assessment of anaemia should involve
laboratory measurement of the following parameters: haemoglobin
(Hb) concentration (to assess the degree of anaemia), mean
corpuscular volume (MCV) and mean corpuscular Hb (MCH) (to assess
the type of anaemia), absolute reticulocyte count (to assess
erythropoietic activity), plasma/serum ferritin concentration (to
assess iron stores), plasma/serum C-reactive protein (CRP) (to
assess inflammation), assessment of occult gastrointestinal blood
loss (to assess possibility of gastrointestinal bleeding). This is
the basic patient evaluation and family physician usually can treat
of most causes of anaemia. Fuller investigations can be done by
specialist (hematologist or nephrologists).
The Hb levels at which therapy with erythropoiesis-stimulating
agents (ESAs) should be initiated, as well as its target Hb level,
remain controversial (6). The EBPG recommend Hb values >11 g/dl
(5), while the K/DOQI clinical practice guidelines and clinical
practice recommendations suggest Hb levels between 11 and 13 g/dl
(7). The use of a target hemoglobin level of 13.5 g per deciliter
(as compared with 11.3 g per deciliter) was associated with
increased risk and no incremental improvement in the quality of
life.(8) Recent trials recommend a target Hb level between 11 and
12 g/dl in CKD patients. (8,9)
1. Kazmi WH, Kausz AT, Khan S, et al. Anemia: An Early
Complication of Chronic Renal Insufficiency. Am J Kidney Dis (2001)
38:803–812.
2. Hsu CY, McCulloch CE, Curhan GC. Epidemiology of anemia
associated with chronic renal insufficiency among adults in the
United States: results from the third national health and nutrition
examination survey. J Am Soc Nephrol (2002) 13:504–510.
3. W. H. Hörl, Y. Vanrenterghem, P. Aljama, P. Brunet, R.
Brunkhorst, L. Gesualdo, I. Macdougall, C. Wanner, and B. Wikström
// OPTA: Optimal treatment of anaemia in patients with chronic
kidney disease (CKD) // Nephrol. Dial. Transplant., June 2007; 22:
iii20 - iii26
4. G. F.M. Strippoli, J. C. Craig, C. Manno, and F. P.
SchenaHemoglobin Targets for the Anemia of Chronic Kidney Disease:
A Meta-analysis of Randomized, Controlled Trials // J. Am. Soc.
Nephrol., December 1, 2004; 15(12): 3154 - 3165.
5. Locatelli F, Aljama P, Barany P, et al. Revised European best
practice guidelines for the management of anaemia in patients with
chronic renal failure. Nephrol Dial Transplant (2004) 19(Suppl
2):ii1–47.
6. Remuzzi G, Ingelfinger JR. Correction of anaemia – payoffs
and problems. N Engl J Med (2006) 355:2141–2146.
7. K/DOQI clinical practice guidelines and clinical practice
recommendations for anemia in chronic kidney disease in adults: Am
J Kidney Dis. (2006) 47([Suppl 3]):S11–S145.
8. Singh AK, Szczech L, Tang KL, et al. Correction of anemia
with epoetin alfa in chronic kidney disease. N Engl J Med (2006)
16:2085–2098.
9. Drueke TB, Locatelli F, Clyne N, et al. Normalization of
hemoglobin level in patients with chronic kidney disease and
anemia. N Engl J Med (2006) 16:2071–2084.
Education and guidelines
Quality of care in CKD
Shared care, referrals
Recommendations, issues for policy makers
Topics for discussion
Best practice examples
References
Appendices