guidelines for the management

Volume 17 Number 1 Supplement 1; March 2006 Safar 1426

Guidelines for the Management of the Mineral Metabolism and Bone Disease

inChronic Kidney Disease Patients

inSaudi Arabia

2006

Preface

In the era of the evidence based medicine and the presence of guidelines for practice around the world, we started to formulate Saudi Guidelines for management of the important problems such as anemia and bone disease in the chronic kidney disease (CKD) patients. The feedback from the renal community on the publication of the guidelines for the management of anemia in the CKD has encouraged the Saudi Center for Organ transplantation to prepare the guidelines for the management of the bone disease and mineral metabolism for the kidney disease centers in the Kingdom of Saudi Arabia (KSA). In addition, the recent survey of attitudes of the physicians towards the management of bone diseases and mineral metabolism in the KSA has demonstrated deficiencies such as the unavailability of protocols that address the management of this important problem in the dialysis centers in the KSA. Currently, there are more than 7500 dialysis patients in the KSA who require attention in terms of the monitoring and management of mineral metabolism and bone disease. Our guidelines aim at having a baseline for the development of sound practices in the context of the local experiences. We intend to develop and maintain these guidelines in order to support the local protocols in each dialysis unit in the KSA. Such support may be fruitful in more quality care management by the providers of the CKD care such as the health planners, physicians and nursing staff.

Faissal A.M. Shaheen MD., & Muhammad Ziad Souqiyyeh MD., On behalf of the advisory committee for the management of mineral metabolism and bone disease in the CKD patients

Advisory Committee for the Management of Mineral Metabolism and Bone Disease in Chronic Kidney Disease

Patients

Dr. Othman AlfureyhDepartment of Medicine,King Faissal Specialist hospital & Research Center,Riyadh.

Dr. Saeed AlghamdiDivision of Nephrology,Department of Medicine,King Faisal Specialist Hospital,Jeddah

Dr. Ali AlharbiDivision of Nephrology,Department Of Medicine,Security Forces Hospital,Riyadh.

Dr. Khaled AlmeshariDepartment of Medicine,King Faissal Specialist hospital & Research Center,Riyadh.

Dr. Abdulla Alkhader AlsayyariDivision of Nephrology,Department of Medicine,King Fahd National Guard Hospital,

Riyadh

Dr. Mohammad AlsulaimanDepartment of Nephrology,Armed Forces HospitalRiyadh

Prof. Jamal Al-Wakeel Division of Nephrology,

Department of Medicine,King Khaled University Hospital,Riyadh.

Dr. Ayman KarkarDivision of Nephrology,Department of Medicine,Dammam Central Hospital,Dammam

Dr. Ali LehbiDivision of Nephrology,Department of Medicine,King Faissal Specialist hospital & Research Center,Riyadh.

Dr. Saadi TaherDepartment of Medicine,King Fahd National Guard hospital Riyadh.

Contents

Topic Page

Introduction …………………………………………………………………………………… S2

Mineral disturbances and bone diseasein the CKD patients in Saudi Arabia ……………………………………………………..... S4

Guidelines statements ………………………………………………………………………… S11 1. Evaluation of calcium and phosphorus metabolism …………………………………….. S12

2. Assessment of bone disease associated with CKD ………………………………………. S12

3. Evaluation of serum phosphorus levels…………………………………………………... S12

4. Restriction of dietary phosphorus in patients with CKD ……………………………… . S13

5. Use of phosphate binders in CKD ………………………………………………………… S13

6. Serum calcium and calcium-phosphorus product ……………………………………….. S137. Prevention and treatment of vitamin D insufficiency and vitamin D deficiency in CKD patients ……………………………………………….. S148. Vitamin D therapy in CKD patient ……………………………………………………….. S15

9. Dialysate concentrations …………………………………………………………………… S16

10. β2 microglobulin amyloidosis …………………………………………………………...... S16

11. Aluminum overload and toxicity in CKD ……………………………………………….. S17

12. Treatment of aluminum toxicity ………………………………………………………….. S17

13. Treatment of bone disease in CKD ……………………………………………………… S17

14. Parathyroidectomy in patients with CKD ………………………………………………. S18

15. Metabolic acidosis ………………………………………………………………………… S19

16. Bone disease in the kidney transplant recipient ……………………………………….. S19

References …………………………………………………………………………………….. S20

Disclaimer ……………………………………………………………………………………... S25

Introduction

There are disturbances of the mineral metabolism and the bone environment in CKD patients. There is increased mortality and morbidity from these abnormalities such as bone pain, increased incidence of bone fractures and deformity, myopathy, muscle pain, and ruptures of tendons and soft tissue calcifications. Hyperphospha-temia also appears to be associated with increased mortality, as well as the elevated blood levels of parathyroid hormone (PTH).1-12 The processes causing disordered mineral metabolism and bone disease

S2 Guidelines for management of bone and mineral metabolism in CKD

have their onset in the early stages of CKD.13 The stages of the CKD are shown in Table 1. Chronic kidney disease is defined as either kidney damage or GFR <60 mL/min/1.73 m2 for ≥ 3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies.14

Table 1. Stages of chronic kidney disease.

Stage

Description GFR(mL/min/1.73 m2 )

1 Kidney damagewith normal or

↑GFR

>90

2 Kidney damagewith mild ↓ GFR

60-89

3 Moderate↓ GFR 30-594 Severe↓ GFR 15-295 Kidney↓ failure <15 (or dialysis)

Patients with CKD almost always develop secondary hyperplasia of the parathyroid glands, resulting in elevated blood levels of parathyroid hormone (PTH). 15-19 This abnormality is due to the hypocalcemia 20,21 that develops during the course of kidney disease and/or to a deficiency of 1, 25-dihydroxycholecalci-ferol (1, 25(OH)2D3) 22-28 that may directly affect the function of the parathyroid glands. With progressive loss of kidney function, a decrease in the number of vitamin D receptors (VDR) and calcium-sensing receptors (CaR) in the parathyroid glands occurs, rendering them more resistant to the action of vitamin D and calcium.29 In addition, the development of hyperphos-phatemia directly affects the function and the growth of the parathyroid glands.30-32

These events will allow secondary hyper-parathyroidism to worsen. The integration of the following factors has been proposed to explain the pathogenesis of the hypo-calcemia; phosphate retention, skeletal resistance to the calcemic action of PTH, and altered vitamin D metabolism. There is a skeletal resistance to the calcium-mobilizing action of PTH, an abnormality that occurs early in the course of both acute and chronic kidney disease and is not reversed by hemodialysis.33-35 The PTH-PTHrP receptors are down regulated in many organs in uremia, including the kidney, liver, and heart, which is not due to the high blood levels of PTH but rather to the PTH-induced elevation in the basal levels of intra-cellular concentrations of calcium (cyto-solic calcium) in those organs. 36

Phosphate retention, which may develop with declining kidney function, plays a role in the disturbances in 1,25(OH)2D3 production. 37-40 The effect of dietary phosphate on kidney production of 1,25(OH)2D3 could be media-ted through changes in transcellular flux of phosphate and/or in the concentration of inorganic phosphorus in kidney cortical cells.41

1,25 (OH)2D3 may have a direct effect on the parathyroid glands. 42,43 The use of calcium compounds in patients with Stage 4 and 5 CKD results in the reduction in the serum levels of phosphorus due to the ability of these compounds to bind phosphate in the intestine. In addition, these calcium compounds cause a rise in serum calcium levels, which would inhibit the parathyroid gland and results in a fall in blood PTH levels. This would be followed by a reduction in serum levels of serum phosphorus. 44-46

Deficiency of 1,25 (OH)2D3 may initiate secondary hyperparathyroidism even in the absence of overt hypocalcemia. 1,25 (OH)2 D3 acts directly on the PTH gene, causing a decrease in its transcription and hence in the synthesis of PTH. The effect of calcium and phosphate on PTH synthesis is post-transcriptional.47 Administration of 1,25 (OH)2D3 to dialysis patients is associated with suppression of PTH secretion and with a shift of the set-point to the left in response to hypocalcemia. 48-51 Moreover, very high concentrations of 1,25 (OH)2D3 induce apo-ptosis of parathyroid gland cells. 52 These observations support the hypothesis that deficiency of this vitamin D metabolite plays an important role in the genesis of secondary hyperparathyroidism in CKD.

The two major types of bone disease that are commonly encountered in patients with CKD are enhanced bone resorption (osteitis fibrosa) and adynamic bone disease (ABD).53-55 This later entity is marked by increased rates of overt fractures and microfractures.56 Calcium uptake by the adynamic bone is reduced, and therefore patients with ABD may develop hypercalcemia if calcium intake is increased or if dialysate calcium is high. 55 Osteosclerosis and osteoporosis may also be contributing factors, while chronic acidosis of CKD may not play a major role in the pathogenesis of bone disease in adult patients with CKD.57,58

Soft-tissue calcification constitutes a serious problem in CKD patients. These extra skeletal calcification may be localized in the arteries (vascular calcification), 59-61 in the eyes (ocular calcification), 62,63 in the visceral organs (visceral calcification), 64-69 around the joints (periarticular calcification),70 and in the skin (cutaneous calcification). 71,72

The chemical nature of soft-tissue calci-fication may vary in different tissues. The calcification found in nonvisceral tissue (periarticular and vascular calcification) consists of hydroxyapatite, with a molar Ca: Mg: P ratio similar to that of bone. In contrast, the calcification found in visceral organs (skeletal and myocardial muscle) is made of amorphous (CaMg)3(PO4)2, which has a much higher magnesium content.73-75 Recent studies suggest that increased calcium intake including diet and calcium salts could increase the risk of the soft-tissue calcifications even without causing hypercalcemia. 76-80

The incidence of vascular calcification increased from 27% in those treated for less than 1 year to 83% in patients treated for more than 8 years.59-61 The vascular calci-fications may involve almost every artery and may be very extensive, rendering the artery so rigid that the pulse is not palpable and the Korotkoff sounds may be difficult to hear during the measurement of the blood pressure. Arterial calcification shows little tendency to regress; in some patients, improvement or disappearance of arterial calcification occurs within months to years after subtotal parathyroidectomy or renal transplantation.81-85

Calcification of the myocardium, coro-nary arteries, and cardiac valves result in congestive heart failure, cardiac arrhyth-mias, ischemic heart disease, and death. Vascular calcification leads to ischemic lesions, soft-tissue necrosis, and difficulties for kidney transplantation. 86,87

Prevention of the disturbances in mineral and bone metabolism and their management early in the course of chronic kidney disease are extremely important in improving patients' quality of life and longevity. These guidelines are intended to aid clinicians in developing an integrated appro-ach to their diagnosis and management of this complicated area, based on the best available evidence. Ongoing research may result in improvements in care. Updating of guide-lines would be a dynamic process that depends on the availability of new information about the subject.

Mineral disturbances and bone disease in the CKD patients in Saudi Arabia

Guidelines for management of bone and mineral metabolism in CKD S3


Over the past 20 years there were a reasonable body of research and reports related to this issue from the dialysis centers in Saudi Arabia. We summarize these reports in chronological sequence in order to stimulate more research in the future:

1. In 1990, Souqiyyeh et al 88 evaluated the effects of high doses calcium carbonate (CaC03) on serum phosphorus (P04--) and serum calcium (Ca ++) in chronic hemodialysis patients, 45 patients (24M, 21F) aged between 19-70 years on regular hemodialysis treatment (RDT) were selected for a four weeks prospe-ctive study. All the patients had been off aluminum hydroxide therapy for four weeks at least before receiving six grams of CaC03 as a standard dose in three divided doses after meals. All the patients had creatinine clearance below 10 ml/min and all were on dialysate calcium conce-ntration of 1.75 mmol/l. The patients were divided into three subgroups; group I renal dialysis treatment (RDT) three times per week and on Vitamin D3 (Vit D3); group II, RDT three times per week without Vit D3; and group III: RDT twice per week and on Vit D3. All the study groups had significant increases of the means of Ca ++ levels and significant decreases of the means of P04 - levels at the end of fourth week of the study. Patients who were on frequent dialysis three times a week and Vit. D3 supple-mentation developed hypercalcemia more frequently than other groups. They conc-luded that calcium carbonate could be used as a phosphate binder in hemodialysis patients. Serum Ca ++ levels need to be checked periodically and Vit D3 supplements may have to dis-continued.

2. In 1993, Huraib et al 89 studied the pattern of renal osteodystrophy in hemodialysis patients in Saudi Arabia. They conducted a multicenter study involving 209 patients. The mean age of the patients was 39.4 ± 14 (18-70) years, 128 were males and 81 females. All patients were on acetate dial-ysate and their mean duration on dialysis was 3.5 ± 1.5 years. The major symptom was bone and joint pain (25.8 %). The mean serum calcium was 2.1 ± 0.26 mmol/l, phosphorus 2.0 ± 0.36 mmol/l, alkaline phosphatase 19.7 ± 14.6 u/l and parathyroid hormone level was 8.9 ± 3.9 mg/ml. The mean serum aluminium (AL) level was 25.4 ± 17.7 µg/l, while that of 1,25 vitamin D3 was 8.1 ± 4.2 ng/l and of fluoride was 92.2 ± 31.4 micrograms/l. The major radiological finding was osteosclerosis (70%). Dual-photon absorp-tionnmetry (DPA) showed low bone mineral density (LBM) in 65% of the patients. Forty-one patients had bone biopsies with AL staining of the biopsies. Of this group, 92% had changes of hyperparathyroidism and 66% of them were pure hyperparathyroidism. Sixty percent of them had variable degrees of AL intoxication. The radiological skeletal survey of those patients could detect abnormalities in only 46% while 70% of them had abnormal bone mineral density (BMD). They concluded that osteosclerosis was the commonest radiological finding in the dialysis patients, while secondary hyperpara-thyroidism was the main histopathological diagnosis in bone biopsy, even in patients with normal skeletal survey. AL intoxication was a significant problem in their population. DPA was more sensitive in detecting bone abnormalities than X-radiography.

3. In 1994, Hussein et al 90 studied 325 patients in one dialysis centre over a 13-year period. There were 19 patients (5.8%) who had pericarditis, 38% radiographic signs of renal bone disease and eight patients required parathyroidectomy. Only two patients had carpal tunnel syndrome.


4. In 1994, George et al 91 described a 40-year-old patient with end-stage renal disease developed features of calci-phylaxis and tumoral calcification after four and half years on regular hemo-dialysis. The patient had hyperphos-phatemia, with high calcium-phosphate index and radiological evidence of hyper-parathyroidism before the onset of symptoms. Conservative management was without success and the patient developed florid symptoms. Parathy-roidectomy was delayed due to un-avoidable circumstances. When it was eventually performed there was a prompt regression of the calcific masses, but not of the vascular calcifications.

5. In 1995, Rassoul et al 92 studied the effect of intravenous calcitriol admini-stration on the PTH level in 14 patients on maintenance hemodialysis with serum PTH levels above 2,000 pmol/l over a 16-week period. There was a significant reduction in the PTH level (65%) and a rise of serum calcium to the normal range. There was a significant reduction in serum PTH levels before the serum calcium concentrations increased; suggesting that calcitriol directly inhibits PTH release with minimal side effects.

6. In 1995, Souqiyyeh et al 93 studied the extent of aluminum related bone disease in 41 patients on regular maintenance hemodialysis in two dialysis centers in Riyadh, Saudi Arabia. There were 22 males and 19 females aged 20 to 70 years (mean 35.5 11.2 years). Thirty eight of the patients were on aluminum based oral phosphate binders. Investi-gations performed included serum calcium, magnesium, aluminum and para-thormone and radiological investiga-tions including skeletal survey and dual photon absorptionmetry. All the patients underwent bone biopsy and the biopsy material was subjected to morphometric studies, including staining for aluminum deposits. The patients were divided into two groups: group 1, (16 patients, 39%) with negative aluminum staining. Bone pain and its distribution as well as fractures were similarly prevented in both groups. The levels of aluminum in the blood was significantly higher in group 2 (32.9 20.2 vs 17.9 11.2 µg/l P<0.05), though it was lower than the lowest accepted toxic level (40 µg/l). There was no significant difference between the two groups in the bio-chemical or hormonal data, frequency of abnormal radiological signs and pattern of bone histology. This study indicated that increased aluminum deposition in the bone was prevalent in patients on main-tenance hemodialysis using aluminum based phosphate binders, but adynamic bone disease was not prevalent. Further studies were recommended on a larger scale to assess the magnitude of the problem.

7. In 1997, Huraib et al 94 conducted this study on 15 chronic hemodialysis patients to evaluate the efficacy of i.v. calcitriol over a 1-year period in the treatment of severe secondary hyper-parathyroidism (HPT), in particular its effect on bone mineral density (BMD) and parathyroid gland mass. Mean age was 39 ± 11.9 (20-65) years and dialysis duration was 58 ± 3 (19-130) months. i.v. calcitriol was given at a dose of 1 µg post-dialysis 3 times/week for 3 weeks; the dose was then adjusted to maintain the total serum calcium at less than 2.88 mmol/l. The maximum dose was 3 μg 3 times/ week. Serum calcium (Ca) and phosphorus (P) were determined prior to treatment, then weekly for 6 weeks and every 2 weeks thereafter. Skeletal survey, dual photon densitometry and parathyroid ultrasound (US) were done prior to treatment and after 1 year. Bone biopsy was done in 10 patients at the beginning of treatment. There was a significant reduction (p < 0.01) in pre-treatment mid-region serum parathyroid hormone


(PTH) from 1,476 ± 895 to 489 ± 485 pmol/l, as well as alkaline phosphatase (p < 0.04) from 236.5 ± 221 to 116.3 ± 49 U/l. This was without a significant increase in serum Ca (2.15 ± 0.25 to 2.44 ± 0.26 mmol/l, p = 0.08). Three patients had recurrent hyper-calcemia which responded to reduction of Ca in dialysate. There was a significant increase in BMD over the spine from 1.071 ± 0.25 to 1.159 ± 0.22 g/cm2 (p < 0.003) with a percent increase of 9.3 - 8.9 % as well as over the femoral neck from 0.834 ± 0.002 to 0.89± 0.09 g/cm2 (p < 0.001) with a percent increase of 7.45-6.81 %. Five patients had enlarged parathyroid glands by US and in 3 of them there was a significant reduction to normal with treatment. Bone biopsy was done in 10 patients. Six patients had pre-dominant hyperparathyroid bone disease and 4 had mixed uremic osteodystrophy. They concluded that long-term i.v. treatment with calcitriol was effective in the treatment of severe secondary HPT. PTH decreased without a significant increase in serum Ca. BMD also increased during therapy.

8. In 1997, Al-Wakeel et al 95 evaluated the serum fluoride (F-) level in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD), which is asso-ciated with risk of renal osteodystrophy and other bone changes. Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 ± 3.28 μmol/l (range 44-51 μmol/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 ± 0.350 μmol /l. Males in control group showed slightly higher F- levels (1.15 ± 0.334, range 0.55-1.9 μmol/l) than females (0.92 ± 0.370, range 0.6-1.5 μmol/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such corre-lation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 ± 1.09, range 0.8-5.2 μmol/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 ±1.04, range 1.8-5.2 μmol/l) was significantly higher than females (2.38 ± 1.08, range 0.8-5.2 μmol/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 ± 1.05) than those with age group 13-20 years (1.42 ± 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 ± 1.97 vs 2.5± 1.137 μmol/l). Of the total 39 patients on dialysis 39% had their serum F-concentration above 3.0 μmol/l, posing risk of renal osteodystrophy.

9. In 1998, Mitwalli et al 96 evaluated renal osteodystrophy (ROD) by performing bone biopsies in 57 patients with end-stage renal failure (ESRF) on dialysis, 46 on hemodialysis (HD) and 11 on peritoneal dialysis (PD). There were 29 males (mean age of 42 years) and 28 females (mean age of 39 years). Relevant presenting clinical features were pruritis in 46 cases, bone pains in 32, acute pseudogout in three, bone deformities in two, conjunctival calci-fication in two, cutaneous calcification in two, and corneal calcification in one. The mean value of predialysis blood investi-gations were as follows: urea 33.9 mmol/L, creatinine 913 μmol/l, bicar-bonate 18 mmol/L, calcium 2.36 mmol/L, albumin 40 g/L, phosphorus 1.69 mmol/L, alkaline phosphatase 178 U/L, parathyroid hormone 543 pmol/L,


magnesium 1.06 mmol/L and aluminum 1.81 mmol/L. Skeletal survey showed no changes in 24 patients (42%), hyper-parathyroid cystic changes of bones in seven, osteoporosis as the predominant features in seven, mixed picture of ROD in 12, subperiosteal resorption of the meta-carpals in two, osteosclerosis (Rugger Jersey Spine) in two and osteomalacia in two patients. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). All patients had low BMD (both LS and FN). Bone biopsy (BBX) revealed mixed picture in 30 cases, predominantly secondary hyper-parathyroid changes in 10, mild hyper-parathyroid changes in five, predo-minant osteoporosis in three, osteo-malacia in four, aplastic (adynamic) bone in four, and aluminum deposition in one. All of the patients who showed evidence of bone involvement on BBX had abnormal BMD suggesting that BMD is a good non-invasive screening test for ROD but indiscriminative for the type of bone disease. They concluded that BBX was still the diagnostic tool to differentiate and classify different types of bone disease.

10. In 1998, al-Homrany et al 97 reported the rare occurrence of diffuse pulmonary calci-nosis in a patient who presented with a pathological femoral fracture during end-stage renal failure. Associated metastatic soft tissue calcification with parathyroid hyperplasia requiring parathyroidectomy was observed. Roentgenologic evidence of hyperparathyroidism with osteitis fibrosa cystica and a high product of the cal-cium and phosphate values were indications for the parathyroidectomy. Literature review of pulmonary calcinosis and multiple soft tissue calcifications was also presented.

11. In 1998, Huraib et al 98 studied the effect of alfacalcidol on lymphocyte phenol-type. There were 15 patients (10 males, 5 females) with a mean age of 54.3 ± 14.4 years who had been on chronic main-tenance hemodialysis for a mean period of 3.2 ± 1.5 years. Intravenous alfacalcidol was given three times weekly during dialysis for duration of 6 months. Our results show a significant increase in natural killer( NK) cells from 0.20 ± 0.12 to 0.27 ± 0.28 (P=0.001), without a significant change in CD2, CD19, CD4, CD8 population, and CD4/CD8 ratio.

12. In 2000, Mitwalli et al 99studied the effect of oral vs intravenous alfacalcidol on secondary hyperparathyroidism and renal osteodystrophy (ROD in 19 ESRD patients, who were on dialysis (13 on hemodialysis and six on peritoneal dia-lysis) for longer than six months and having serum parathormone levels at least four times normal and serum calcium less than 2.1 mmol/L, were randomly allocated to treatment with oral or intra-venous (i.v.) alfacalcidol for a period of 12 months. There were six patients on hemodialysis (HD) and three on peri-toneal dialysis (PD) in the oral treatment group while in the i.v. group there were seven patients on HD and three on PD. Clinical and serial biochemical assess-ments showed no statistically significant difference between the orally- and i.v.-treated patients in terms of suppressing secondary hyperparathyroidism and osteodystrophy. However, patients with features of mild ROD on bone histology had more satisfactory changes in bioche-mistry when compared to others. The results further supported the use of intermittent oral alfacalcidol in ESRD patients because of its cost effectiveness, ease of administration and convenience, especially for peritoneal dialysis patients.

13. Gacha et al 100 described a patient with periarticular calcifications that resolved spontaneously post transplantation.


14. In 2004, Shaheen et al 101 evaluated the use of a calcium- and metal-free phos-phate-binding polymer, sevelamer, in hemodialysis and compared it with the standard calcium-based phosphate binder in an open-label, randomized, cross-over study. After a 2-week phos-phate binder washout period, stable hemodialysis patients were given either sevelamer or calcium carbonate, and the dosages were titrated to achieve phos-phate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Twenty patients from the Dialysis Unit of King Fahd Hospital, Jeddah, Kingdom of Saudi Arabia, were recruited for the study between March 2003 and June 2003. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-3.3± 2.2 mg/dl) and calcium carbonate (-3.9± 2.8 mg/dl). Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/l (11.0 mg/dl) while receiving calcium carbonate versus 26% of patients receiving sevelamer (p<0.05). The incidence of hypercalcemia for sevel-amer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 13% mean decrease in serum cholesterol levels. They concluded that sevelamer was effective in contro-lling hyperphosphatemia without an increase in the incidence of hypercal-cemia seen with calcium carbonate. This agent appeared quite effective in the treatment of hyperphosphatemia in hemo-dialysis patients and its usage may be advantageous in the treatment of dialysis.

15. In 2006, Souqiyyeh et al 102 studied the attitude of the physicians in the Kingdom of Saudi Arabia (KSA) towards the treatment of the bone disease in the dialysis centers. They sent a question-naire to 168 physicians; the heads of the 146 active dialysis centers in the KSA and 34 more consultants working in them. This covered decision makers in 110 (75.3 %) centers in ministry of health (MOH), 14 (9.5%) centers in govern-mental (non-MOH) and 22 (15.2 %) centers in private sector for a population of more than 7214 chronic hemodialysis (HD) patients. The study was conducted from April-June 2005. There were 134 out of 168 (78.6%) physicians who answered the questionnaire from 134 (91.7%) of the dialysis centers that cover 7030 (97.6%) of the dialysis patients in the KSA. There were 133 (99.3%) of the respondents who believed that the bone disease and meta-static calcifications in the HD patients is an important problem, 71 (53.4%) had a protocol for management of bone disease at their centers, while 87(67.4%) believed that the current results of management of bone disease were satisfactory at their centers. There were 112 (84.2%) respondents who would check calcium once a month on the dialysis patients and 110 (82.7%) who would check phosphorus once a month, while only 33 (24.6%) would check PTH once every three months and 44(32.8%) did not have this latter test available in their centers. There were 63(47.4%) respon-dents who would check the bone X-rays of the hands and clavicles once every year, while 51(38.4%) would perform the X-rays as indicated by the clinical status. There were 125(94.7%) respon-dents who would never have a bone biopsy performed on HD patients, and 84(64.6%) would not do any more tests besides those mentioned above to evaluate the bone disease in their dialysis patients. There were 87 (64.9%) respondents who would aim by therapy at mid normal serum calcium level and 75(56.8 %) would target the mid normal serum phosphorus level, while only 36(29.3%) would target three times normal level of the PTH. There were 81(60.4) respondents who believed that continued abnormality of


these parameters carry more risk of morbidity and mortality in a larger percentage of chronic dialysis patients than anemia or inefficient dialysis. There were only 58(43.3%) respondents who believed that sevelamer would be a safer phosphate binder than calcium or metal based one, while the calcium based phosphate binder was still considered by 66 (49.3%) respondents as a safer binder. There were 68(51.5%) respondents who considered 1600 mg elemental calcium daily dose as a phosphate binder the maximum recommended dose for the dialysis patients and 69(52.3%) believed that this dose was adequate to control phosphorus in the dialysis patients. Almost all the respondents use vitamin D mostly by daily oral administration or a combi-nation with intravenous route (59% vs. 41% respectively). There were 59 (44.4%) respondents who believed that sevelamer plus vitamin D were a better regimen to control PTH than Calcium based phosphate binder plus vitamin D, While 51(38.3%) had no idea about this issue. There were 57(42.5%) respondents who believed that high intake of calcium would increase the risk of vascular and metastatic calcifications without hyper-calcemia in the dialysis patients, while 43(32.1%) had no idea. There were 58(43.9%) respondents who believed that the role of calcimmetics was well established in the management of bone disease in dialysis patients, while 48(36.4%) had no idea. In comparison to non-MOH and private dialysis centers, there was a significantly lower percentage of the MOH centers to have protocol for management of bone disease in the dialysis patients, higher percentage of unavailability of PTH assay, lower tendency of the physicians to target low normal level of phosphorus and higher percentage to target normal levels of PTH in the dialysis patients. In addition, MOH physicians had significantly less tendency to consider sevelamer the best phosphate binder for the dialysis patients and less believe that high intake of calcium can increase the risk of vascular and metastatic calcifications without hypercalcemia in the dialysis patients. They concluded that the current practices

concerning the bone disease management in the dialysis centers in the KSA require refinement in terms of the need to enforce the use of a protocol to guide evaluation and therapy in each dialysis unit. There was also a need to increase the awareness of physicians in those centers to the importance of the details of such treatment and the national guidelines in this regard.


G U I D E L I N E SG U I D E L I N E SS T A T E M E N T S


1. Evaluation of Calcium and Phosphorus Metabolism

1.1 Serum levels of calcium, phosphorus, and intact plasma parathyroid hormone (PTH) should be measured in all patients with CKD and GFR <60 mL/min/1.73 m2. The frequency of these measure-ments should be based on the stage of chronic kidney disease, (Table 2).

Table 2. Frequency of measurement of PTH and calcium/phosphorus by stage of CKDCKD Stag

e

GFR Range

(mL/min/

1.73 m2)

Measurement of PTH

Measurement of Calcium/ Phosphorus

3 30-59 Every 12months

Every 12 months

4 15-29 Every 3 months

Every 3 months

5 <15 or dialysis

Every 3 months

Every month

1.2 These measurements should be made more frequently if the patient is receiving concomitant therapy for the abnormalities in the serum levels of calcium, phosphor-rus or PTH.

1.3 Measurement of plasma PTH levels may be done less frequently for those with levels within the low end of the target levels (Table 3).

1.4 The target range of plasma levels of intact PTH in the various stages of CKD are denoted in Table 3.

Table 3. Target range of intact plasma PTH by stage of CKD

CKDStage

GFR Range(mL/min/1.73 m2)

Target intact" PTH pg/mL [pmol/L]

3 30-59 35-70 [3.85-7.7]

4 15-29 70-110 [7.7-12.1]

5 <15 or dialysis 150-300 [16.5-33.0]

2. Assessment of Bone Disease associated with CKD

2.1 The most accurate diagnostic test for determining the type of bone disease associated with CKD is iliac crest bone biopsy with double tetracycline labeling and bone histomorphometric analysis.

2.2 It is not necessary to perform bone biopsy for most situations in clinical practice. However, a bone biopsy should be considered in patients with kidney failure (Stage 5) who have:

2.2a Pathological fractures, which are fractu-res with minimal or no trauma.

2.2b Intact plasma PTH levels 100 - 500 pg/mL (11.0 - 55.0 mol/L) (in CKD Stage 5) with coexisting conditions such as unexplained hypercalcemia, severe bone pain, or unexplained increases in bone alkaline phosphatase activity.

2.2c Suspected aluminum bone disease, based upon clinical symptoms or history of aluminum exposure.

2.3 Bone radiographs are not indicated for the assessment of bone disease of CKD, but they are useful in detecting severe peripheral vascular calcification and bone disease due to β2-microglobulin amyloi-dosis.

2.4 Bone mineral density (BMD) should be measured by dual energy X-ray absorptio-metry (DEXA) in patients with fractures and in those with known risk factors for osteoporosis.

3. Evaluation of Serum Phosphorus levels

3.1 In CKD patients (Stages 3 and 4), the serum level of phosphorus should be maintained at or above 0.87 mmol/L and no higher than 1.48 mmol/L.

3.2 In CKD patients with kidney failure (Stage 5) and those treated with hemo-dialysis or peritoneal dialysis, the serum levels of phosphorus should be maintained


between 1.13 - 1.78 mmol/L. 4. Restriction of Dietary Phosphorus in

Patients with CKD

4.1 Dietary phosphorus should be restricted to 800 to 1,000 mg/day (adjusted for dietary protein needs) when the serum phosphorus levels are elevated > 1.49 mmol/L (Stages 3 and 4 of CKD) and >1.78 mmol/L in those with kidney failure (Stage 5).

4.2 Dietary phosphorus should be restricted to 800 to 1,000 mg/day (adjusted to die-tary protein needs) when the plasma levels of intact PTH are elevated above target range of the CKD stage.

4.3 The serum phosphorus levels should be monitored every month following the initiation of dietary phosphorus restriction.

5. Use of Phosphate Binders in CKD

In CKD Patients (Stages 3 and 4): 5.1 If phosphorus or intact PTH levels cannot

be controlled within the target range, despite dietary phosphorus restriction, phosphate binders should be prescribed.

5.2 Calcium-based phosphate binders are effective in lowering serum phosphorus levels and may be used as the initial binder therapy.

In CKD Patients with Kidney Failure (Stage 5):

5.3 Both calcium-based phosphate binders and other noncalcium-, non-metal phosphate-binding agents (such as sevelamer HCl) are effective in lowering serum phos-phorus levels and either may be used as the primary therapy.

5.4 In dialysis patients who remain hyper-phosphatemic (serum phosphorus >1.78 mmol/L) despite the use of either of calcium-based phosphate binders or other non-calcium-, nonaluminum-, nonmag-nesium-phosphate-binding agents, a combination of both should be used.

5.5 The total dose of elemental calcium

provided by the calcium-based phosphate binders should not exceed 1,500 mg/day, and the total intake of eleme-ntal calcium (including dietary calcium) should not exceed 2,000 mg/day.

5.6 Calcium-based phosphate binders should not be used in dialysis patients who are hypercalcemic (corrected serum calcium of >2.54 mmol/L), or whose plasma PTH levels are <150 pg/mL (16.5 pmol/L) on two consecutive measu-rements.

5.7 Noncalcium-containing phosphate bind-ers are preferred in dialysis patients with severe vascular and/or other soft tissue calcifications.

5.8 In patients with serum phosphorus levels >2.26 mmol/L, aluminum-based phosphate binders may be used as a short-term therapy (4 weeks), and for one course only, to be replaced there-after by other phosphate binders. In such patients, more frequent dialysis should also be considered.

6. Serum Calcium and Calcium-Phosphorus Product

In CKD Patients (Stages 3 and 4):

6.1 The serum levels of corrected total calcium should be maintained within the "normal" range for the laboratory used.

In CKD Patients with Kidney Failure (Stage 5):

6.2 Serum levels of corrected total calcium should be maintained within the normal range for the laboratory used, preferably toward the lower end 2.10 - 2.37 mmol/L.

6.3 In the event corrected total serum calcium level exceeds 2.54 m mol/L, therapies that cause serum calcium to rise should be adjusted as follows:

6.3a In patients taking calcium-based pho-sphate binders, the dose should be reduced or therapy switched to a non-


calcium-, non-aluminum-, non-magne-sium-containing phosphate binder.

6.3b In patients taking active vitamin D sterols, the dose should be reduced or therapy discontinued until the serum levels of corrected total calcium return to the target range (2.10 - 2.37 mmol/L).

6.3c If hypercalcemia (serum levels of corrected total calcium > 2.54 mmol/L) persists despite modification of therapy with vitamin D and/or discontinuation of calcium-based phosphate binders, dialysis using low dialysate calcium (1.25 - 1.5 mmol/L) may be used for 3 - 4 weeks.

In CKD Patients (Stages 3 to 5):

6.4 Total elemental calcium intake (including both dietary calcium intake and calcium-based phosphate binders) should not exceed 2,000 mg/day.

6.5 The serum calcium-phosphorus product should be maintained at < 4.5 mmol2L2. This is best achieved by controlling ser-um levels of phosphorus within the target range.

6.6 Patients whose serum levels of corrected total calcium are below the lower limit for the laboratory used (< 2.10 mmol/L) should receive therapy to increase serum calcium levels if:

6.6a There are clinical symptoms of hypocal-cemia such as paresthesia, Chvostek's and Trousseau's signs, bronchospasm, laryngospasm, tetany, and/or seizures.

6.6b The plasma intact PTH level is above the target range for the CKD Stage.

6.7 Therapy for hypocalcemia should include calcium salts such as calcium carbonate and/or oral vitamin D sterols.

7. Prevention and Treatment of Vitamin D insufficiency and Vitamin D

Deficiency in CKD Patients

In CKD Patients (Stages 3 and 4):

7.1 If plasma intact PTH is above the target range for the stage of CKD, serum 25-hydroxyvitamin D should be measured at first encounter. If it is normal, repeat annually.

7.2 If the serum level of 25-hydroxy vitamin D is <30 ng/mL, supplementa-tion with vitamin D2, (ergocalciferol) should be initiated, (Table 4).

7.3 Following initiation of vitamin D therapy:

7.3a The use of ergocalciferol therapy should be integrated with the serum calcium and phosphorus.

7.3b The serum levels of corrected total calcium and phosphorus should be mea-sured at least every 3 months.

7.3c If the serum levels of corrected total calcium exceeds 2.54 mmol/L, discontinue ergocalciferol therapy and all forms of vitamin D therapy.

7.3d If the serum phosphorus exceeds 1.49 mmol/L, add or increase the dose of phosphate binder. If hyperphosphatemia persists, discontinue vitamin D therapy.

Table 4. Recommended supplementation for vitamin D deficiency/insufficiency in patients with CKD stages 3 and 4Serum 25(OH) ng/mL

[nmol/L]Definition Ergo-calciferol Dose

(Vitamin D2)Comment

<5[12]

Severe vitamin Ddeficiency

50,000 lU/wk orally x 12 wks; then monthly

OR500,000 IU as single I.M.

dose

Duration x 6 months.Measure 25(OH)D levels

after 6 months

Assure patient adherence

5-15

[12-37]

Mild vitamin D deficiency orally 50,000 lU/wk x 4 weeks,

then 50,000 IU/month

Duration x 6 months.

measure 25(OH)D levels after 6 months

16-30 Vitamin D insufficiency 50,000 lU/month orally


[40-75]7.3d If the serum phosphorus exceeds 1.49

mmol/L, add or increase the dose of phosphate binder. If hyperphospha-temia persists, discontinue vitamin D therapy.

7.3e Once patients are replete with vitamin D, continued supplementation with a vitamin-D-containing multi-vitamin pre-paration should be used with annual reassessment of serum levels of 25-hydroxyvitamin D, and the continued assessment of corrected total calcium and phosphorus every 3 months.

In CKD Patients with Kidney Failure(Stage 5):

7.4 Therapy with an active vitamin D sterol (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) should be provided if the plasma levels of intact PTH is >300 pg/mL (300 ng/L).

8. Vitamin D Therapy in CKD Patients

8A Active Vitamin D Therapy in Patients with Stages 3 and 4 CKD

8A.1 In patients with CKD Stages 3 and 4, therapy with an active oral vitamin D sterol (calcitriol, alfacalcidol, or doxer-calciferol) is indicated when serum levels of 25(OH)-vitamin D are >30 ng/mL, and plasma levels of intact PTH are above the target range for the CKD stage.

8A.la Treatment with an active vitamin D sterol should be under taken only in patients with serum levels of corrected total calcium< 2.37 mmol/L and serum phosphorus<1.47 mmol/L.

8A.lb Vitamin D sterols should not be prescribed for patients with rapidly worsening kidney function or those who are noncompliant with medica-tions or follow-up.

8A.2 During therapy with vitamin D sterols, serum levels of calcium and phosphorus should be monitored at least every

month after initiation of therapy for the first 3 months, then every 3 months thereafter. Plasma PTH levels should be measured at least every 3 months for 6 months, and every 3 months thereafter.

8A.3 Dosage adjustments for patients receiving active vitamin D sterol therapy should be made as follows:

8A.3a If plasma levels of intact PTH fall below the target range for the CKD stage, hold active vitamin D sterol therapy until plasma levels of intact PTH rise to above the target range, then resume treatment with the dose of active vitamin D sterol reduced by half. If the lowest daily dose of the active vitamin D sterol is being used, reduce to alternate-day dosing.

8A.3b If serum levels of corrected total calcium exceed 2.37 mmol/L, hold active vitamin D sterol therapy until serum calcium returns to < 2.37 mmol/L, then resume treatment at half the previous dose. If the lowest daily dose of the active vitamin D sterol is being used, reduce to alternate-day dosing.

8A.3c If serum levels of phosphorus rise to >1.49 mmol/ L, hold active vitamin D therapy, initiate or increase dose of phosphate binder until the levels of serum phosphorus fall to < 1.49 mmol/L; then resume the prior dose of active vitamin D sterol.

8B. Vitamin D Therapy in Patients on Dialysis (CKD Stage 5)

8B.1 Patients treated with hemodialysis or peritoneal dialysis with serum levels of intact PTH levels >300 pg/mL (33.0 pmol/L) should receive an active vitamin D sterol (such as calcitriol, alfacalcidol, paricalcitol, or doxercalciferol; to reduce the serum levels of PTH to a target range of 150 - 300 pg/mL (16.5 - 33.0 pmol/L).

8B.la The intermittent, intravenous admini-stration of calcitriol is more effective


than daily oral calcitriol in lowering serum PTH levels.

8B.lb In patients with corrected serum calcium and/or phosphorus levels above the target range, a trial of alternative vitamin D analogs, such as paricalcitol or doxercalciferol may be warranted, (Table 5).

8B.2 When therapy with vitamin D sterols is initiated or the dose is increased, serum levels of calcium and phosphorus should be monitored at least every 2 weeks for 1 month and then monthly thereafter. The plasma PTH should be measured monthly for at least 3 months and then every 3 months once target levels of PTH are achieved.

8B.3 For patients treated with peritoneal dialysis, oral doses of calcitriol (0.5 - 1.0 µg) or doxercalciferol (2.5 - 5.0 µg) can be given 2 or 3 times weekly. Alternatively, a lower dose of calcitriol (0.25 µg) can be administered daily.

8B.4 When either hemodialysis or peritoneal dialysis patients are treated with active vitamin D sterols, management should integrate the changes in serum calcium, serum phosphorus, and plasma PTH.

9. Dialysate Concentrations

9.1 The dialysate calcium concentration in hemodialysis or peritoneal dialysis should be 1.25 mmol/L.

9.2 Higher or lower dialysate calcium levels are indicated in selected patients.

10. β 2-Microglobulin Amyloidosis

10.1 Screening for α2-microglobulin amyloi-dosis, including measurement of serum levels of β2-microglobuIin, is not recom-mended.

10.1a No currently available therapy (except kidney transplantation) can stop disease progression of β2-microglobulin amyloi-dosis or provide symptommatic relief.

10.1b Kidney transplant should be considered to stop disease progression or provide symptomatic relief in patients with β2-microgIobulin amyloidosis.

10.1c In patients with evidence of, or at risk for β2-microglobulin amyloidosis noncupro-phane, high-flux dialyzers should be used.

Table 5. Recommended initial dosing for vitamin D sterols by serum PTH, serum calcium and serum phosphorus

Plasma PTH pg/ml

or[pmol/L]

Serum calciummmol/L

SerumPhosphorus

mmol/L

Doseper HD

Calcitriol

Doseper HD

Paricalcitol

Doseper HD

Doxercalciferol

300-600[33-66]

<2.37 <1.78 IV:0.5-1.5 µgOral:0.5-1.5 µg

2.5-5.0 µg Oral: 5 µgIV: 2 µg

600-1000[66-110]

< 2.37 <1.78 IV:1.0-3.0 µgOral:1-4 µg

6.0-10 µg Oral: 5-10 µgIV: 2-4 µg

>1000[110]

<2.50 < 1.78 IV:3.0-5.0 µgOral:3-7µg

10-15 µg Oral: 10-20 µgIV: 4-8 µg


11. Aluminum overload and toxicity in CKD

11.1 To prevent aluminum toxicity, the regular administration of aluminum should be avoided and the dialysate concentration of aluminum should be maintained at<10 µg/L.

11.1a CKD patients ingesting aluminum should not receive citrate salts simulta-neously.

11.2 To assess aluminum exposure and the risk of aluminum toxicity, serum alumi-num levels should be measured at least yearly and every 3 months in those receiving aluminum-containing medications.

11.2a Baseline levels of serum aluminum should be <20 µg/L.

11.3 A deferoxamine (DFO) test should be performed if there are elevated serum aluminum levels (60 to 200 µg/L); clinical signs and symptoms of aluminum toxicity, or prior to parathyroid surgery if the patient has had aluminum exposure.

11.3a The test is done by infusing 5 mg/kg of DFO during the last hour of the dialysis session with a serum aluminum measured before DFO infusion and 2 days later, before the next dialysis session.

11.3b The test is considered positive if the increment of serum aluminum is > 50 µg/L.

11.3c A DFO test should not be performed if the serum levels of aluminum are >200 µg/L to avoid DFO-induced neurotoxicity.

11.4 The presence of aluminum bone disease can be predicted by a rise in serum aluminum of ≥ 50 µg/L following DFO challenge combined with plasma levels of intact PTH of < 150 pg/mL (16.5 pmol/L). However, the gold standard for the diagnosis of aluminum bone disease is a bone biopsy showing increased aluminum staining of the bone surface (> 15% to 25%) using aluminum stain and often adynamic bone or osteomalacia.

12. Treatment of Aluminum Toxicity

12.1 In all patients with baseline serum aluminum levels > 60 µg/L, a positive DFO test, or clinical symptoms consi-stent with aluminum toxicity, the source of aluminum should be identified and eliminated.

12.2 In symptomatic patients with serum aluminum levels > 60 µg/L but < 200 µg/L or a rise of aluminum after DFO >50 µg/L, DFO should be given to treat the aluminum overload.

12.3 To avoid DFO-induced neurotoxicity in patients with serum aluminum >200 µg/L, DFO should not be given until intensive dialysis (6 days per week) with high-flux dialysis membrane and a dialysate alumi-num level of < 5 µg/L and until the pre-dialysis serum aluminum level has been reduced to <200 µg/L.

13. Treatment of Bone Disease in CKD

The therapeutic approach to bone disease in CKD is based on its specific type i.e. high-turnover and mixed bone disease; osteomalacia; and adynamic bone disease.

13A. Hyperparathyroid (High-Turnover) and mixed (High-Turnover with

Mineralization Defect) Bone Disease

13A.1 In CKD patients who have plasma levels of intact PTH >70 pg/mL (7.7 pmol/L) in stage 3 or >110 pg/mL (12.1 pmol/L) in stage 4 on more than 2 consecutive measurements, dietary phos-phate intake should be restricted. If this is ineffective in lowering plasma PTH levels, calcitriol, or its analogs alfacal-cidol or doxercalciferol, should be given to prevent or ameliorate bone disease.

13A.2 In CKD patients who have elevated plasma levels of intact PTH (>300 pg/mL [33.0 pmol/L]) in stage 5, calci-triol or its analogs doxercalciferol, alfacalcidol or paricalcitol should be used to reverse the bone features of PTH


overactivity (i.e. high-turnover bone disease), and to treat defective mine-ralization.

13B. Osteomalacia

13B.1 Osteomalacia due to aluminum toxicity should be prevented in dialysis patients by maintaining aluminum concentration in dialysate fluid at <10 µg/L and avoiding the use of aluminum-containing compo-unds (including sucralfate).

13B.2 Aluminum overload leading to aluminum bone disease should be treated with deferoxamine (DFO).

13B.3 Osteomalacia due to vitamin D2 or D3 deficiency or phosphate depletion, though uncommon, should be treated with vita-min D2 or D3 supplementation and/or phosphate administration, respectively.

13B.3a If osteomalacia due to vitamin D deficiency fails to respond to ergo-calciferol or cholecalciferol, particu-larly in patients with kidney failure (Stage 5), treatment with an active vitamin D sterol may be given.

13B.3b Doses of phosphate supplementation should be adjusted upwards until normal serum level of phosphorus is achieved.

13C. Adynamic Bone Disease

13C.1 Adynamic bone disease in stage 5 CKD (as determined either by bone biopsy or intact PTH <100 pg/ml [11.0 pmol/L]) should be treated by allowing plasma levels of intact PTH to rise in order to increase bone turnover.

13C.la This can be accomplished by decreasing doses of calcium-based phosphate binders and vitamin D or eliminating such therapy.

14. Parathyroidectomy in patients with CKD

14.1 Parathyroidectomy should be recom-mended in patients with severe hyper-

parathyroidism (persistent serum levels of intact PTH >800 pg/mL [88.0 pmol/L]), associated with hypercalcemia and/or hyperphosphatemia that are refra-ctory to medical therapy.

14.2 Effective surgical therapy of severe hyperparathyroidism can be accompli-shed by subtotal parathyroidectomy, or total parathyroidectomy with parathy-roid tissue autotransplantation.

14.3 In patients who undergo parathyroid-ectomy the following should be done:

14.3a The blood level of ionized calcium should be measured every 4 to 6 hours for the first 48 to 72 hours after surgery, and then twice daily until stable.

14.3b If the blood levels of ionized or corrected total calcium fall below normal (<0.9 mmol/L or corres-ponding to corrected total calcium of 1.8 mmol/L), a calcium gluconate infusion should be initiated at a rate of 1 to 2 mg elemental calcium per kilogram body weight per hour and adjusted to maintain an ionized calcium in the normal range (1.15 to 1.36 mmol/L).

14.3c The calcium infusion should be gradually reduced when the level of ionized calcium attains the normal range and remains stable.

14.3d When oral intake is possible, the patient should receive calcium carbonate 1 to 2 g 3 times a day, as well as calcitriol of up to 2 µg/day, and these therapies should be adjusted as necessary to maintain the level of ionized calcium in the normal range.

14.3e If the patient was receiving phos-phate binders prior to surgery, this therapy may need to be disconti-nued or reduced as dictated by the levels of serum phosphorus, and some patients may require phosphate supplements.

14.4 Imaging of parathyroid glands with"Tc-Sestamibi scan, ultrasound, CTscan, or MRI should be done prior to re-exploration parathyroid surgery.


15. Metabolic Acidosis

15.1 In CKD Stages 3, 4 and 5, the serum level of total CO2 should be measured.

15.1a The frequency of these measurements should be based on the stage of CKD, (Table 6).

Table 6. Frequency for measurement of serum levels of total Co2CKD Stage GFR Range

ml/min/1.73m2Frequency of Measurement

(At least)3 30-59 every 12

months4 15-29 every 3 months

5 <15 every month

15.2 In these patients, serum levels of total CO2 should be maintained at > 22 mmol/L. If necessary, supplemental alkali salts (such as NaHCo3 300-600 orally three times daily) should be given to achieve this goal.

16. Bone Disease in the Kidney Transplant Recipient

16.1 Serum levels of calcium, phosphorus, total CO2 and plasma intact PTH should be monitored following kidney transplant-tation.

16.1a The frequency of these measure-ments should be based on the time following transplantation.

16.2 During the first week after kidney transplantation, serum levels of phos-phorus should be measured daily. Kidney transplant recipients who develop persi-stently low levels of serum phosphate (<0.81 mmol/L) should be treated with phosphate supplementation.

16.3 To minimize bone mass loss and oste-onecrosis, the immunosuppressive regimen should be adjusted to the lowest effective dose of glucocorticoids.

16.4 Kidney transplant recipients should have bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA) to assess the presence or development of osteoporosis.

16.4a DEXA scans should be obtained at time of transplant, 1 year, and 2 years post-transplant.

16.4b If BMD t-score is equal to or ≤ 2 at the time of the transplant or at subsequent evaluations, therapy with parenteral amino-bisphosphonates should be considered.

16.5 Treatment of disturbances in bone and mineral metabolism is deter-mined by the level of kidney function in the transplant recipient.

Table 7. Frequency of measurement of calcium, phosphorus, PTH and total CO2 after kidney transplantation

Parameter First 3 Months 3months to 1 year

Calcium Every 2 weeks MonthlyPhosphorus Every 2 weeks Monthly

PTH Monthly Every 3 monthsTotal CO2 Every 2 weeks Monthly


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Disclaimer

These Guidelines are based upon the best information available at the time of publication. They are designed to provide information and assist decision-making. They are not intended to define a standard of care, and should not be construed as one. Neither should they be interpreted as prescribing an exclusive course of management.

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Every health-care professional making use of these Guidelines is responsible for evaluating the appropriateness of applying them in the setting of any particular clinical situation.


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