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  • 1. Volume 17 Number 1 Supplement 1; March 2006 Safar 1426 Guidelines for the Management of the Mineral Metabolism and Bone Disease in Chronic Kidney Disease Patients in Saudi Arabia 2006
  • 2. 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
  • 3. Advisory Committee for the Management of Mineral Metabolism and Bone Disease in Chronic Kidney Disease Patients Dr. Othman Alfureyh Dr. Mohammad Alsulaiman Department of Medicine, Department of Nephrology, King Faissal Specialist hospital Armed Forces Hospital & Research Center, Riyadh Riyadh. Prof. Jamal Al-Wakeel Dr. Saeed Alghamdi Division of Nephrology, Division of Nephrology, Department of Medicine, Department of Medicine, King Khaled University Hospital, King Faisal Specialist Hospital, Riyadh. Jeddah Dr. Ayman Karkar Dr. Ali Alharbi Division of Nephrology, Division of Nephrology, Department of Medicine, Department Of Medicine, Dammam Central Hospital, Security Forces Hospital, Dammam Riyadh. Dr. Ali Lehbi Dr. Khaled Almeshari Division of Nephrology, Department of Medicine, Department of Medicine, King Faissal Specialist hospital King Faissal Specialist hospital & Research Center, & Research Center, Riyadh. Riyadh. Dr. Abdulla Alkhader Alsayyari Dr. Saadi Taher Division of Nephrology, Department of Medicine, Department of Medicine, King Fahd National Guard hospital King Fahd National Guard Hospital, Riyadh. Riyadh
  • 4. Contents Topic Page Introduction …………………………………………………………………………………… S2 Mineral disturbances and bone disease in 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 ……………………………………….. S13 7. Prevention and treatment of vitamin D insufficiency and vitamin D deficiency in CKD patients ……………………………………………….. S14 8. 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
  • 5. S2 Guidelines for management of bone and mineral metabolism in CKD Introduction affect the function of the parathyroid glands. With progressive loss of kidney There are disturbances of the mineral function, a decrease in the number of vitamin D receptors (VDR) and calcium- metabolism and the bone environment in sensing receptors (CaR) in the parathyroid CKD patients. There is increased mortality glands occurs, rendering them more resistant and morbidity from these abnormalities to the action of vitamin D and calcium. 29 such as bone pain, increased incidence of In addition, the development of hyperphos- bone fractures and deformity, myopathy, phatemia directly affects the function and muscle pain, and ruptures of tendons and the growth of the parathyroid glands.30-32 soft tissue calcifications. Hyperphospha- These events will allow secondary hyper- parathyroidism to worsen. The integration temia also appears to be associated with of the following factors has been proposed increased mortality, as well as the elevated to explain the pathogenesis of the hypo- blood levels of parathyroid hormone calcemia; phosphate retention, skeletal (PTH).1-12 The processes causing disordered resistance to the calcemic action of PTH, mineral metabolism and bone disease have and altered vitamin D metabolism. their onset in the early stages of CKD.13 The There is a skeletal resistance to the stages of the CKD are shown in Table 1. calcium-mobilizing action of PTH, an Chronic kidney disease is defined as either abnormality that occurs early in the course kidney damage or GFR <60 mL/min/1.73 m2 of both acute and chronic kidney disease for ≥ 3 months. Kidney damage is defined as and is not reversed by hemodialysis. 33-35 pathological abnormalities or markers of The PTH-PTHrP receptors are down regulated damage, including abnormalities in blood or in many organs in uremia, including the urine tests or imaging studies.14 kidney, liver, and heart, which is not due to the high blood levels of PTH but rather to the Table 1. Stages of chronic kidney disease. PTH-induced elevation in the basal levels of intra-cellular concentrations of calcium (cyto- Stag Description GFR solic calcium) in those organs. 36 e (mL/min/1.73 m2 ) Phosphate retention, which may develop 1 Kidney damage >90 with declining kidney function, plays a role with normal or in the disturbances in 1,25(OH)2D3 production. ↑GFR 37-40 The effect of dietary phosphate on kidney 2 Kidney damage 60-89 with mild ↓ GFR production of 1,25(OH)2D3 could be media- 3 Moderate↓ GFR 30-59 ted through changes in transcellular flux of 4 Severe↓ GFR 15-29 phosphate and/or in the concentration of 5 Kidney↓ failure <15 (or dialysis) inorganic phosphorus in kidney cortical cells.41 1,25 (OH)2D3 may have a direct Patients with CKD almost always effect on the parathyroid glands. 42,43 The use develop secondary hyperplasia of the of calcium compounds in patients with parathyroid glands, resulting in elevated Stage 4 and 5 CKD results in the reduction blood levels of parathyroid hormone in the serum levels of phosphorus due to the (PTH).15-19 This abnormality is due to the ability of these compounds to bind phosphate hypocalcemia 20,21 that develops during the course of kidney disease and/or to a in the intestine. In addition, these calcium deficiency of 1, 25-dihydroxycholecalci- compounds cause a rise in serum calcium ferol (1, 25(OH)2D3) 22-28 that may directly levels, which would inhibit the parathyroid
  • 6. Guidelines for management of bone and mineral metabolism in CKD S3 gland and results in a fall in blood PTH levels. consists of hydroxyapatite, with a molar Ca: This would be followed by a reduction in Mg: P ratio similar to that of bone. In serum levels of serum phosphorus. 44-46 contrast, the calcification found in visceral organs (skeletal and myocardial muscle) is Deficiency of 1,25 (OH)2D3 may initiate made of amorphous (CaMg)3(PO4)2, which secondary hyperparathyroidism even in the has a much higher magnesium content.73-75 absence of overt hypocalcemia. 1,25 (OH)2 Recent studies suggest that increased D3 acts directly on the PTH gene, causing a calcium intake including diet and calcium decrease in its transcription and hence in salts could increase the risk of the soft- the synthesis of PTH. The effect of calcium tissue calcifications even without causing and phosphate on PTH synthesis is post- hypercalcemia.76-80 transcriptional.47 Administration of 1,25 (OH)2D3 to dialysis patients is associated The incidence of vascular calcification with suppression of PTH secretion and with increased from 27% in those treated for less a shift of the set-point to the left in response than 1 year to 83% in patients treated for to hypocalcemia. 48-51 Moreover, very high more than 8 years.59-61 The vascular calci- concentrations of 1,25 (OH)2D3 induce apo- fications may involve almost every artery ptosis of parathyroid gland cells. 52 These and may be very extensive, rendering the observations support the hypothesis that artery so rigid that the pulse is not palpable deficiency of this vitamin D metabolite plays and the Korotkoff sounds may be difficult an important role in the genesis of secondary to hear during the measurement of the hyperparathyroidism in CKD. blood pressure. Arterial calcification shows little tendency to regress; in some patients, The two major types of bone disease that improvement or disappearance of arterial are commonly encountered in patients with calcification occurs within months to years CKD are enhanced bone resorption (osteitis after subtotal parathyroidectomy or renal fibrosa) and adynamic bone disease transplantation.81-85 (ABD).53-55 This later entity is marked by increased rates of overt fractures and Calcification of the myocardium, coro- microfractures.56 Calcium uptake by the nary arteries, and cardiac valves result in adynamic bone is reduced, and therefore congestive heart failure, cardiac arrhyth- patients with ABD may develop mias, ischemic heart disease, and death. hypercalcemia if calcium intake is Vascular calcification leads to ischemic increased or if dialysate calcium is high. 55 lesions, soft-tissue necrosis, and difficulties Osteosclerosis and osteoporosis may also be for kidney transplantation. 86,87 contributing factors, while chronic acidosis Prevention of the disturbances in mineral of CKD may not play a major role in the and bone metabolism and their management pathogenesis of bone disease in adult early in the course of chronic kidney disease patients with CKD.57,58 are extremely important in improving patients' Soft-tissue calcification constitutes a quality of life and longevity. serious problem in CKD patients. These These guidelines are intended to aid extra skeletal calcification may be localized in clinicians in developing an integrated appro- the arteries (vascular calcification), 59-61 in the ach to their diagnosis and management of this eyes (ocular calcification), 62,63 in the visceral complicated area, based on the best available organs (visceral calcification), 64-69 around evidence. Ongoing research may result in the joints (periarticular calcification),70 and improvements in care. Updating of guide- in the skin (cutaneous calcification). 71,72 lines would be a dynamic process that depends The chemical nature of soft-tissue calci- on the availability of new information about fication may vary in different tissues. The calcification found in nonvisceral tissue the subject. (periarticular and vascular calcification)
  • 7. S4 Guidelines for management of bone and mineral metabolism in CKD Mineral disturbances and checked periodically and Vit D3 supplements bone disease in the CKD may have to dis-continued. patients in Saudi Arabia 2. In 1993, Huraib et al 89 studied the pattern of renal osteodystrophy in hemodialysis Over the past 20 years there were a patients in Saudi Arabia. They conducted a reasonable body of research and reports multicenter study involving 209 patients. The related to this issue from the dialysis centers in mean age of the patients was 39.4 ± 14 Saudi Arabia. We summarize these reports in (18-70) years, 128 were males and 81 chronological sequence in order to stimulate females. All patients were on acetate dial- more research in the future: ysate and their mean duration on dialysis was 3.5 ± 1.5 years. The major symptom was 88 1. In 1990, Souqiyyeh et al evaluated the bone and joint pain (25.8 %). The mean effects of high doses calcium carbonate serum calcium was 2.1 ± 0.26 mmol/l, (CaC03) on serum phosphorus (P04--) and phosphorus 2.0 ± 0.36 mmol/l, alkaline serum calcium (Ca ++) in chronic phosphatase 19.7 ± 14.6 u/l and parathyroid hemodialysis patients, 45 patients (24M, 21F) hormone level was 8.9 ± 3.9 mg/ml. The aged between 19-70 years on regular mean serum aluminium (AL) level was 25.4 ± hemodialysis treatment (RDT) were 17.7 µg/l, while that of 1,25 vitamin D3 was selected for a four weeks prospe-ctive 8.1 ± 4.2 ng/l and of fluoride was 92.2 ± 31.4 study. All the patients had been off micrograms/l. The major radiological aluminum hydroxide therapy for four weeks finding was osteosclerosis (70%). Dual- at least before receiving six grams of CaC03 photon absorp-tionnmetry (DPA) showed as a standard dose in three divided doses low bone mineral density (LBM) in 65% of after meals. All the patients had creatinine the patients. Forty-one patients had bone clearance below 10 ml/min and all were on biopsies with AL staining of the biopsies. Of dialysate calcium conce-ntration of 1.75 this group, 92% had changes of mmol/l. The patients were divided into three hyperparathyroidism and 66% of them were subgroups; group I renal dialysis treatment pure hyperparathyroidism. Sixty percent of (RDT) three times per week and on Vitamin them had variable degrees of AL D3 (Vit D3); group II, RDT three times per intoxication. The radiological skeletal survey week without Vit D3; and group III: RDT of those patients could detect abnormalities twice per week and on Vit D3. All the in only 46% while 70% of them had study groups had significant increases of abnormal bone mineral density (BMD). They the means of Ca ++ levels and significant concluded that osteosclerosis was the decreases of the means of P04 - levels at commonest radiological finding in the the end of fourth week of the study. dialysis patients, while secondary hyperpara- Patients who were on frequent dialysis thyroidism was the main histopathological three times a week and Vit. D3 supple- diagnosis in bone biopsy, even in patients Guidelines for management of moreand mineral metabolismskeletal survey. AL intoxication mentation developed hypercalcemia bone with normal in CKD S5 frequently than other groups. They conc- was a significant problem in their population. luded that calcium carbonate could be used DPA was more sensitive in detecting bone as a phosphate binder in hemodialysis abnormalities than X-radiography. patients. Serum Ca ++ levels need to be 3. In 1994, Hussein et al 90 studied 325 patients in one dialysis centre over a 13-
  • 8. year period. There were 19 patients (5.8%) and radiological investiga-tions including who had pericarditis, 38% radiographic skeletal survey and dual photon signs of renal bone disease and eight absorptionmetry. All the patients patients required parathyroidectomy. Only underwent bone biopsy and the biopsy two patients had carpal tunnel syndrome. material was subjected to morphometric 91 4.In 1994, George et al described a 40- studies, including staining for aluminum year-old patient with end-stage renal disease deposits. The patients were divided into two developed features of calci-phylaxis and groups: group 1, (16 patients, 39%) with tumoral calcification after four and half negative aluminum staining. Bone pain and years on regular hemo-dialysis. The patient its distribution as well as fractures were had hyperphos-phatemia, with high calcium- similarly prevented in both groups. The levels phosphate index and radiological evidence of of aluminum in the blood was significantly hyper-parathyroidism before the onset of higher in group 2 (32.9 ± 20.2 vs 17.9 ± 11.2 symptoms. Conservative management was µg/l P<0.05), though it was lower than the without success and the patient developed lowest accepted toxic level (40 µg/l). There florid symptoms. Parathy-roidectomy was was no significant difference between the delayed due to un-avoidable circumstances. two groups in the bio-chemical or hormonal When it was eventually performed there was data, frequency of abnormal radiological a prompt regression of the calcific masses, but signs and pattern of bone histology. This not of the vascular calcifications. study indicated that increased aluminum 5.In 1995, Rassoul et al 92 studied the effect deposition in the bone was prevalent in of intravenous calcitriol admini-stration on patients on main-tenance hemodialysis using the PTH level in 14 patients on aluminum based phosphate binders, but maintenance hemodialysis with serum PTH adynamic bone disease was not prevalent. levels above 2,000 pmol/l over a 16-week Further studies were recommended on a period. There was a significant reduction in Guidelines for management ofthe magnitude of the S6 larger scale to assess bone and mineral metabolism in CKD the PTH level (65%) and a rise of serum problem. calcium to the normal range. There was a 7. In 1997, Huraib et al 94 conducted this study significant reduction in serum PTH levels on 15 chronic hemodialysis patients to before the serum calcium concentrations evaluate the efficacy of i.v. calcitriol over a increased; suggesting that calcitriol directly 1-year period in the treatment of severe inhibits PTH release with minimal side secondary hyper-parathyroidism (HPT), in effects. particular its effect on bone mineral density 6. In 1995, Souqiyyeh et al 93 studied the (BMD) and parathyroid gland mass. Mean extent of aluminum related bone disease in age was 39 ± 11.9 (20-65) years and 41 patients on regular maintenance dialysis duration was 58 ± 3 (19-130) hemodialysis in two dialysis centers in months. i.v. calcitriol was given at a dose Riyadh, Saudi Arabia. There were 22 of 1 µg post-dialysis 3 times/week for 3 males and 19 females aged 20 to 70 years weeks; the dose was then adjusted to (mean 35.5 ± 11.2 years). Thirty eight of maintain the total serum calcium at less the patients were on aluminum based oral than 2.88 mmol/l. The maximum dose was phosphate binders. Investi-gations 3 μg 3 times/ week. Serum calcium (Ca) performed included serum calcium, and phosphorus (P) were determined prior magnesium, aluminum and para-thormone to treatment, then weekly for 6 weeks and
  • 9. every 2 weeks thereafter. Skeletal survey, l) of F- content in drinking water. Control dual photon densitometry and parathyroid subjects showed a mean serum F- ultrasound (US) were done prior to concentration of 1.08 ± 0.350 μmol /l. treatment and after 1 year. Bone biopsy was Males in control group showed slightly done in 10 patients at the beginning of higher F- levels (1.15 ± 0.334, range treatment. There was a significant 0.55-1.9 μmol/l) than females (0.92 ± reduction (p < 0.01) in pre-treatment mid- 0.370, range 0.6-1.5 μmol/l). Mean serum region serum parathyroid hormone (PTH) F- concentration did not correlate from 1,476 ± 895 to 489 ± 485 pmol/l, as significantly with age and sex among well as alkaline phosphatase (p < 0.04) from control subjects, whereas such corre-lation 236.5 ± 221 to 116.3 ± 49 U/l. This was was observed in patients with ESRD on without a significant increase in serum Ca dialysis. Mean serum F- concentration was (2.15 ± 0.25 to 2.44 ± 0.26 mmol/l, p = significantly higher in patients on dialysis 0.08). Three patients had recurrent hyper- (2.67 ± 1.09, range 0.8-5.2 μmol/l) than calcemia which responded to reduction of Ca normal controls. When grouped according in dialysate. There was a significant to sex, the mean serum F- concentration in increase in BMD over the spine from 1.071 males (3.05 ±1.04, range 1.8-5.2 μmol/l) ± 0.25 to 1.159 ± 0.22 g/cm2 (p < 0.003) was significantly higher than females (2.38 with a percent increase of 9.3 - 8.9 % as ± 1.08, range 0.8-5.2 μmol/l). When well as over the femoral neck from 0.834 ± patients were grouped according to age, it 0.002 to 0.89± 0.09 g/cm2 (p < 0.001) with was observed that F- concentration was a percent increase of 7.45-6.81 %. Five significantly higher in patients with age patients had enlarged parathyroid glands by groups 21-70 (2.86 ± 1.05) than those with US and in 3 of them there was a significant age group 13-20 years (1.42 ± 0.531). Thus reduction to normal with treatment. Bone F- concentration correlated with age and biopsy was done in 10 patients. Six patients sex, being higher in males and above 20 had pre-dominant hyperparathyroid bone years. Despite appreciable clearance of F- disease and 4 had mixed uremic (39-90%) across the peritoneum, patients on osteodystrophy. They concluded that long- CAPD showed 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/
  • 10. Guidelines for management of bone and mineral metabolism in CKD S7 higher serum F- concentration than those (adynamic) bone in four, and aluminum on HD (3.1 ± 1.97 vs 2.5± 1.137 μmol/l). deposition in one. All of the patients who Of the total 39 patients on dialysis 39% showed evidence of bone involvement on had their serum F-concentration above 3.0 BBX had abnormal BMD suggesting that μmol/l, posing risk of renal BMD is a good non-invasive screening test osteodystrophy. for ROD but indiscriminative for the type 9.In 1998, Mitwalli et al 96 evaluated renal of bone disease. They concluded that BBX osteodystrophy (ROD) by performing bone was still the diagnostic tool to differentiate biopsies in 57 patients with end-stage renal and classify different types of bone disease. failure (ESRF) on dialysis, 46 on 10. In 1998, al-Homrany et al 97 reported the hemodialysis (HD) and 11 on peritoneal rare occurrence of diffuse pulmonary calci- dialysis (PD). There were 29 males (mean nosis in a patient who presented with a age of 42 years) and 28 females (mean age pathological femoral fracture during end-stage of 39 years). Relevant presenting clinical renal failure. Associated metastatic soft features were pruritis in 46 cases, bone tissue calcification with parathyroid pains in 32, acute pseudogout in three, hyperplasia requiring parathyroidectomy was bone deformities in two, conjunctival calci- observed. Roentgenologic evidence of fication in two, cutaneous calcification in two, hyperparathyroidism with osteitis fibrosa and corneal calcification in one. The mean cystica and a high product of the cal-cium value of predialysis blood investi-gations and phosphate values were indications for were as follows: urea 33.9 mmol/L, the parathyroidectomy. Literature review of creatinine 913 μmol/l, bicar-bonate 18 mmol/ pulmonary calcinosis and multiple soft tissue L, calcium 2.36 mmol/L, albumin 40 g/L, calcifications was also presented. phosphorus 1.69 mmol/L, alkaline 11. In 1998, Huraib et al 98 studied the effect phosphatase 178 U/L, parathyroid hormone of alfacalcidol on lymphocyte phenol-type. 543 pmol/L, magnesium 1.06 mmol/L and There were 15 patients (10 males, 5 aluminum 1.81 mmol/L. Skeletal survey females) with a mean age of 54.3 ± 14.4 showed no changes in 24 patients (42%), years who had been on chronic main- hyper-parathyroid cystic changes of bones tenance hemodialysis for a mean period of in seven, osteoporosis as the predominant 3.2 ± 1.5 years. Intravenous alfacalcidol features in seven, mixed picture of ROD in was given three times weekly during 12, subperiosteal resorption of the meta- dialysis for duration of 6 months. Our carpals in two, osteosclerosis (Rugger results show a significant increase in Jersey Spine) in two and osteomalacia in natural killer( NK) cells from 0.20 ± 0.12 two patients. Bone mineral density (BMD) to 0.27 ± 0.28 (P=0.001), without a was measured by dual x-ray significant change in CD2, CD19, CD4, absorptiometry in the lumbar spine (LS) CD8 population, and CD4/CD8 ratio. and femoral neck (FN). All patients had 12. In 2000, Mitwalli et al 99studied the effect low BMD (both LS and FN). Bone biopsy of oral vs intravenous alfacalcidol on (BBX) revealed mixed picture in 30 cases, secondary hyperparathyroidism and renal predominantly secondary hyper-parathyroid osteodystrophy (ROD in 19 ESRD changes in 10, mild hyper-parathyroid patients, who were on dialysis (13 on changes in five, predo-minant osteoporosis hemodialysis and six on peritoneal dia- in three, osteo-malacia in four, aplastic lysis) for longer than six months and having
  • 11. S8 Guidelines for management of bone and mineral metabolism in CKD serum parathormone levels at least four and June 2003. There was a similar times normal and serum calcium less than decrease in serum phosphate values over 2.1 mmol/L, were randomly allocated to the course of the study with both sevelamer treatment with oral or intra-venous (i.v.) (-3.3± 2.2 mg/dl) and calcium carbonate alfacalcidol for a period of 12 months. (-3.9± 2.8 mg/dl). Fifty-two percent of There were six patients on hemodialysis patients developed serum calcium greater (HD) and three on peri-toneal dialysis (PD) than 2.75 mmol/l (11.0 mg/dl) while in the oral treatment group while in the i.v. receiving calcium carbonate versus 26% of group there were seven patients on HD and patients receiving sevelamer (p<0.05). The three on PD. Clinical and serial incidence of hypercalcemia for sevel-amer biochemical assess-ments showed no was not different from the incidence of statistically significant difference between hypercalcemia during the washout period. the orally- and i.v.-treated patients in terms Patients treated with sevelamer also of suppressing secondary sustained a 13% mean decrease in serum hyperparathyroidism and osteodystrophy. cholesterol levels. They concluded that However, patients with features of mild sevelamer was effective in contro-lling ROD on bone histology had more hyperphosphatemia without an increase in satisfactory changes in bioche-mistry when the incidence of hypercal-cemia seen with compared to others. The results further calcium carbonate. This agent appeared supported the use of intermittent oral quite effective in the treatment of alfacalcidol in ESRD patients because of its hyperphosphatemia in hemo-dialysis patients cost effectiveness, ease of administration mineral metabolism in CKD advantageous in the Guidelines for management of bone and and its usage may be S9 and convenience, especially for peritoneal treatment of dialysis. dialysis patients. 15.In 2006, Souqiyyeh et al 102 studied the 100 13.Gacha et al described a patient with attitude of the physicians in the Kingdom of periarticular calcifications that resolved Saudi Arabia (KSA) towards the treatment spontaneously post transplantation. of the bone disease in the dialysis centers. 101 14.In 2004, Shaheen et al evaluated the They sent a question-naire to 168 use of a calcium- and metal-free phos- physicians; the heads of the 146 active phate-binding polymer, sevelamer, in dialysis centers in the KSA and 34 more hemodialysis and compared it with the consultants working in them. This covered standard calcium-based phosphate binder decision makers in 110 (75.3 %) centers in in an open-label, randomized, cross-over ministry of health (MOH), 14 (9.5%) centers study. After a 2-week phos-phate binder in govern-mental (non-MOH) and 22 (15.2 washout period, stable hemodialysis %) centers in private sector for a patients were given either sevelamer or population of more than 7214 chronic calcium carbonate, and the dosages were hemodialysis (HD) patients. The study was titrated to achieve phos-phate control over conducted from April-June 2005. There an 8-week period. After a 2-week washout were 134 out of 168 (78.6%) physicians period, patients crossed over to the who answered the questionnaire from 134 alternate agent for 8 weeks. Twenty patients (91.7%) of the dialysis centers that cover from the Dialysis Unit of King Fahd Hospital, 7030 (97.6%) of the dialysis patients in the Jeddah, Kingdom of Saudi Arabia, were KSA. There were 133 (99.3%) of the recruited for the study between March 2003 respondents who believed that the bone
  • 12. disease and meta-static calcifications in the phosphate binder the maximum HD patients is an important problem, 71 recommended dose for the dialysis patients (53.4%) had a protocol for management of and 69(52.3%) believed that this dose was bone disease at their centers, while adequate to control phosphorus in the 87(67.4%) believed that the current results dialysis patients. Almost all the of management of bone disease were respondents use vitamin D mostly by daily satisfactory at their centers. There were oral administration or a combi-nation with 112 (84.2%) respondents who would check intravenous route (59% vs. 41% calcium once a month on the dialysis respectively). There were 59 (44.4%) patients and 110 (82.7%) who would check respondents who believed that sevelamer phosphorus once a month, while only 33 plus vitamin D were a better regimen to (24.6%) would check PTH once every control PTH than Calcium based phosphate three months and 44(32.8%) did not have binder plus vitamin D, While 51(38.3%) this latter test available in their centers. had no idea about this issue. There were There were 63(47.4%) respon-dents who 57(42.5%) respondents who believed that would check the bone X-rays of the hands high intake of calcium would increase the and clavicles once every year, while risk of vascular and metastatic calcifications 51(38.4%) would perform the X-rays as without hyper-calcemia in the dialysis indicated by the clinical status. There were patients, while 43(32.1%) had no idea. 125(94.7%) respon-dents who would never There were 58(43.9%) respondents who have a bone biopsy performed on HD believed that the role of calcimmetics was patients, and 84(64.6%) would not do any well established in the management of more tests besides those mentioned above bone disease in dialysis patients, while to evaluate the bone disease in their 48(36.4%) had no idea. In comparison to dialysis patients. There were 87 (64.9%) non-MOH and private dialysis centers, respondents who would aim by therapy at there was a significantly lower percentage mid normal serum calcium level and of the MOH centers to have protocol for 75(56.8 %) would target the mid normal management of bone disease in the dialysis serum phosphorus level, while only patients, higher percentage of unavailability 36(29.3%) would target three times normal Guidelines for assay, lower tendencymineral metabolism in CKD S10 of PTH management of bone and of the level of the PTH. There were 81(60.4) physicians to target low normal level of respondents who believed that continued phosphorus and higher percentage to target abnormality of these parameters carry more normal levels of PTH in the dialysis risk of morbidity and mortality in a larger patients. In addition, MOH physicians had percentage of chronic dialysis patients than significantly less tendency to consider anemia or inefficient dialysis. There were sevelamer the best phosphate binder for the only 58(43.3%) respondents who believed dialysis patients and less believe that high that sevelamer would be a safer phosphate intake of calcium can increase the risk of binder than calcium or metal based one, vascular and metastatic calcifications while the calcium based phosphate binder without hypercalcemia in the dialysis was still considered by 66 (49.3%) patients. They concluded that the current respondents as a safer binder. There were practices 68(51.5%) respondents who considered 1600 mg elemental calcium daily dose as a
  • 13. 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.
  • 14. Guidelines for management of bone and mineral metabolism in CKD S11 GUIDELINES STATEMENTS
  • 15. S12 Guidelines for management of bone and mineral metabolism in CKD 1. Evaluation of Calcium and 2. Assessment of Bone Disease Phosphorus Metabolism associated with CKD 1.1Serum levels of calcium, phosphorus, 2.1 The most accurate diagnostic test for and intact plasma parathyroid hormone determining the type of bone disease (PTH) should be measured in all patients associated with CKD is iliac crest with CKD and GFR <60 mL/min/1.73 m . 2 bone biopsy with double tetracycline The frequency of these measure-ments labeling and bone histomorphometric should be based on the stage of chronic analysis. kidney disease, (Table 2). 2.2 It is not necessary to perform bone biopsy for most situations in clinical Table 2. Frequency of measurement of PTH and practice. However, a bone biopsy should calcium/phosphorus by stage of CKD be considered in patients with kidney CKD GFR Measuremen Measurement failure (Stage 5) who have: Stag Range t of PTH of Calcium/ 2.2a Pathological fractures, which are fractu- e (mL/min Phosphorus res with minimal or no trauma. / 2.2b Intact plasma PTH levels 100 - 500 1.73 m2) pg/mL (11.0 - 55.0 mol/L) (in CKD 3 30-59 Every Every 12 Stage 5) with coexisting conditions such 12months months as unexplained hypercalcemia, severe 4 15-29 Every 3 Every 3 bone pain, or unexplained increases in months months bone alkaline phosphatase activity. 5 <15 or Every 3 Every month dialysis months 2.2c Suspected aluminum bone disease, based upon clinical symptoms or history of aluminum exposure. 1.2These measurements should be made 2.3 Bone radiographs are not indicated for more frequently if the patient is receiving the assessment of bone disease of CKD, concomitant therapy for the abnormalities in but they are useful in detecting severe the serum levels of calcium, phosphor-rus or peripheral vascular calcification and bone PTH. disease due to β2-microglobulin amyloi- 1.3Measurement of plasma PTH levels may be dosis. done less frequently for those with levels within 2.4 Bone mineral density (BMD) should be the low end of the target levels (Table 3). measured by dual energy X-ray absorptio- 1.4The target range of plasma levels of intact metry (DEXA) in patients with fractures PTH in the various stages of CKD are and in those with known risk factors for denoted in Table 3. osteoporosis. Table 3. Target range of intact plasma PTH by 3. Evaluation of Serum Phosphorus stage of CKD levels CKD GFR Range Target intact" PTH 3.1 In CKD patients (Stages 3 and 4), the Stag (mL/min/1.73 m2) pg/mL [pmol/L] serum level of phosphorus should be e maintained at or above 0.87 mmol/L 3 30-59 35-70 [3.85-7.7] and no higher than 1.48 mmol/L. 3.2 In CKD patients with kidney failure 4 15-29 70-110 [7.7-12.1] (Stage 5) and those treated with hemo- dialysis or peritoneal dialysis, the serum 5 <15 or dialysis 150-300 [16.5-33.0] levels of phosphorus should be maintained between 1.13 - 1.78 mmol/L.
  • 16. Guidelines for management of bone and mineral metabolism in CKD S13 4. Restriction of Dietary Phosphorus in binders should not exceed 1,500 mg/day, Patients with CKD and the total intake of eleme-ntal calcium (including dietary calcium) should not 4.1 Dietary phosphorus should be restricted exceed 2,000 mg/day. to 800 to 1,000 mg/day (adjusted for 5.6Calcium-based phosphate binders should dietary protein needs) when the serum not be used in dialysis patients who are phosphorus levels are elevated > 1.49 hypercalcemic (corrected serum calcium of mmol/L (Stages 3 and 4 of CKD) and >2.54 mmol/L), or whose plasma PTH levels >1.78 mmol/L in those with kidney are <150 pg/mL (16.5 pmol/L) on two failure (Stage 5). consecutive measu-rements. 4.2 Dietary phosphorus should be restricted 5.7Noncalcium-containing phosphate bind- to 800 to 1,000 mg/day (adjusted to die- ers are preferred in dialysis patients with tary protein needs) when the plasma severe vascular and/or other soft tissue levels of intact PTH are elevated above calcifications. target range of the CKD stage. 5.8In patients with serum phosphorus levels 4.3 The serum phosphorus levels should be >2.26 mmol/L, aluminum-based phosphate monitored every month following the binders may be used as a short-term therapy initiation of dietary phosphorus restriction. (4 weeks), and for one course only, to be replaced there-after by other phosphate 5. Use of Phosphate Binders in CKD binders. In such patients, more frequent dialysis should also be considered. In CKD Patients (Stages 3 and 4): 6. Serum Calcium and Calcium- 5.1 If phosphorus or intact PTH levels cannot Phosphorus Product be controlled within the target range, despite dietary phosphorus restriction, In CKD Patients (Stages 3 and 4): phosphate binders should be prescribed. 5.2 Calcium-based phosphate binders are 6.1 The serum levels of corrected total effective in lowering serum phosphorus calcium should be maintained within the levels and may be used as the initial binder "normal" range for the laboratory used. therapy. In CKD Patients with Kidney Failure In CKD Patients with Kidney Failure (Stage 5): (Stage 5): 6.2 Serum levels of corrected total calcium 5.3Both calcium-based phosphate binders and should be maintained within the normal other noncalcium-, non-metal phosphate- range for the laboratory used, preferably binding agents (such as sevelamer HCl) are toward the lower end 2.10 - 2.37 mmol/ effective in lowering serum phos-phorus L. levels and either may be used as the 6.3 In the event corrected total serum primary therapy. calcium level exceeds 2.54 m mol/L, 5.4In dialysis patients who remain hyper- therapies that cause serum calcium to phosphatemic (serum phosphorus >1.78 rise should be adjusted as follows: mmol/L) despite the use of either of calcium- 6.3a In patients taking calcium-based pho- based phosphate binders or other non- sphate binders, the dose should be calcium-, nonaluminum-, nonmag-nesium- reduced or therapy switched to a non- phosphate-binding agents, a combination of Guidelines calcium-, non-aluminum-,mineral metabolism in CKD S14 for management of bone and non-magne- both should be used. sium-containing phosphate binder. 5.5The total dose of elemental calcium 6.3b In patients taking active vitamin D provided by the calcium-based phosphate sterols, the dose should be reduced or
  • 17. therapy discontinued until the serum 6.7 Therapy for hypocalcemia should levels of corrected total calcium return to include calcium salts such as calcium the target range (2.10 - 2.37 mmol/L). carbonate and/or oral vitamin D sterols. 6.3c If hypercalcemia (serum levels of corrected total calcium > 2.54 mmol/L) 7. Prevention and Treatment of persists despite modification of therapy Vitamin D insufficiency and Vitamin D with vitamin D and/or discontinuation Deficiency in CKD Patients of calcium-based phosphate binders, dialysis using low dialysate calcium In CKD Patients (Stages 3 and 4): (1.25 - 1.5 mmol/L) may be used for 3 - 4 weeks. 7.1 If plasma intact PTH is above the target range for the stage of CKD, serum 25- In CKD Patients (Stages 3 to 5): hydroxyvitamin D should be measured at first encounter. If it is normal, repeat 6.4 Total elemental calcium intake annually. (including both dietary calcium intake 7.2 If the serum level of 25-hydroxy and calcium-based phosphate binders) vitamin D is <30 ng/mL, supplementa- should not exceed 2,000 mg/day. tion with vitamin D2, (ergocalciferol) 6.5 The serum calcium-phosphorus product should be initiated, (Table 4). should be maintained at < 4.5 mmol2L2. 7.3 Following initiation of vitamin D therapy: This is best achieved by controlling ser- um levels of phosphorus within the 7.3a The use of ergocalciferol therapy target range. should be integrated with the serum 6.6 Patients whose serum levels of calcium and phosphorus. corrected total calcium are below the 7.3b The serum levels of corrected total lower limit for the laboratory used (< calcium and phosphorus should be mea- 2.10 mmol/L) should receive therapy to sured at least every 3 months. increase serum calcium levels if: 7.3c If the serum levels of corrected total 6.6a There are clinical symptoms of hypocal- calcium exceeds 2.54 mmol/L, discontinue cemia such as paresthesia, Chvostek's ergocalciferol therapy and all forms of and Trousseau's signs, bronchospasm, vitamin D therapy. laryngospasm, tetany, and/or seizures. 7.3d If the serum phosphorus exceeds 1.49 6.6b The plasma intact PTH level is above mmol/L, add or increase the dose of the target range for the CKD Stage. 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 4 Serum 25(OH) ng/mL Definition Ergo-calciferol Dose Comment [nmol/L] (Vitamin D2) Duration x 6 months. Severe vitamin D 50,000 lU/wk orally x 12 Measure 25(OH)D levels <5 deficiency wks; then monthly [12] after 6 months OR 500,000 IU as single I.M. Assure patient adherence dose 5-15 Mild vitamin D deficiency orally Duration x 6 months. 50,000 lU/wk x 4 weeks, measure 25(OH)D levels [12-37] then 50,000 IU/month after 6 months 16-30 Vitamin D insufficiency 50,000 lU/month orally [40-75]
  • 18. Guidelines for management of bone and mineral metabolism in CKD S15 7.3d If the serum phosphorus exceeds 1.49 first 3 months, then every 3 months mmol/L, add or increase the dose of thereafter. Plasma PTH levels should be phosphate binder. If hyperphospha- measured at least every 3 months for 6 temia persists, discontinue vitamin D months, and every 3 months thereafter. therapy. 8A.3 Dosage adjustments for patients 7.3e Once patients are replete with vitamin receiving active vitamin D sterol D, continued supplementation with a therapy should be made as follows: vitamin-D-containing multi-vitamin pre- 8A.3a If plasma levels of intact PTH fall paration should be used with annual below the target range for the CKD reassessment of serum levels of 25- stage, hold active vitamin D sterol hydroxyvitamin D, and the continued therapy until plasma levels of intact assessment of corrected total calcium PTH rise to above the target range, and phosphorus every 3 months. then resume treatment with the dose of active vitamin D sterol reduced by In CKD Patients with Kidney Failure half. If the lowest daily dose of the (Stage 5): active vitamin D sterol is being used, reduce to alternate-day dosing. 7.4 Therapy with an active vitamin D sterol 8A.3b If serum levels of corrected total (calcitriol, alfacalcidol, paricalcitol, or calcium exceed 2.37 mmol/L, hold doxercalciferol) should be provided if the active vitamin D sterol therapy until plasma levels of intact PTH is >300 serum calcium returns to < 2.37 pg/mL (300 ng/L). mmol/L, then resume treatment at half the previous dose. If the lowest daily 8. Vitamin D Therapy in CKD Patients dose of the active vitamin D sterol is being used, reduce to alternate-day 8A Active Vitamin D Therapy in Patients dosing. with Stages 3 and 4 CKD 8A.3c If serum levels of phosphorus rise to >1.49 mmol/ L, hold active vitamin 8A.1 In patients with CKD Stages 3 and 4, D therapy, initiate or increase dose of therapy with an active oral vitamin D phosphate binder until the levels of sterol (calcitriol, alfacalcidol, or doxer- serum phosphorus fall to < 1.49 mmol/ calciferol) is indicated when serum levels L; then resume the prior dose of active of 25(OH)-vitamin D are >30 ng/mL, vitamin D sterol. and plasma levels of intact PTH are above the target range for the CKD 8B. Vitamin D Therapy in Patients on stage. Dialysis (CKD Stage 5) 8A.la Treatment with an active vitamin D sterol should be under taken only in 8B.1 Patients treated with hemodialysis or patients with serum levels of corrected peritoneal dialysis with serum levels of total calcium< 2.37 mmol/L and serum intact PTH levels >300 pg/mL (33.0 phosphorus<1.47 mmol/L. pmol/L) should receive an active vitamin 8A.lb Vitamin D sterols should not be D sterol (such as calcitriol, alfacalcidol, prescribed for patients with rapidly paricalcitol, or doxercalciferol; to reduce worsening kidney function or those the serum levels of PTH to a target who are noncompliant with medica- range of 150 - 300 pg/mL (16.5 - 33.0 tions or follow-up. pmol/L). 8A.2 During therapy with vitamin D sterols, 8B.la The intermittent, intravenous admini- serum levels of calcium and phosphorus stration of calcitriol is more effective should be monitored at least every than daily oral calcitriol in lowering month after initiation of therapy for the serum PTH levels.
  • 19. S16 Guidelines for management of bone and mineral metabolism in CKD 8B.lb In patients with corrected serum 9. Dialysate Concentrations calcium and/or phosphorus levels above the target range, a trial of 9.1 The dialysate calcium concentration in alternative vitamin D analogs, such as hemodialysis or peritoneal dialysis paricalcitol or doxercalciferol may be should be 1.25 mmol/L. warranted, (Table 5). 9.2 Higher or lower dialysate calcium levels 8B.2 When therapy with vitamin D sterols is are indicated in selected patients. initiated or the dose is increased, serum levels of calcium and phosphorus should 10. β 2-Microglobulin Amyloidosis be monitored at least every 2 weeks for 1 month and then monthly thereafter. 10.1 Screening for α2-microglobulin amyloi- The plasma PTH should be measured dosis, including measurement of serum monthly for at least 3 months and then levels of β2-microglobuIin, is not recom- every 3 months once target levels of PTH mended. are achieved. 10.1a No currently available therapy (except 8B.3 For patients treated with peritoneal kidney transplantation) can stop disease dialysis, oral doses of calcitriol (0.5 - progression of β2-microglobulin amyloi- 1.0 µg) or doxercalciferol (2.5 - 5.0 µg) dosis or provide symptommatic relief. can be given 2 or 3 times weekly. 10.1b Kidney transplant should be considered Alternatively, a lower dose of calcitriol to stop disease progression or provide (0.25 µg) can be administered daily. symptomatic relief in patients with β2- 8B.4 When either hemodialysis or peritoneal microgIobulin amyloidosis. dialysis patients are treated with active 10.1c In patients with evidence of, or at risk for vitamin D sterols, management should β2-microglobulin amyloidosis noncupro- integrate the changes in serum calcium, phane, high-flux dialyzers should be used. serum phosphorus, and plasma PTH. Table 5. Recommended initial dosing for vitamin D sterols by serum PTH, serum calcium and serum phosphorus Plasma PTH pg/ Serum Serum Dose Dose Dose ml calcium Phosphorus per HD per HD per HD or mmol/L mmol/L Calcitriol Paricalcitol Doxercalciferol [pmol/L] 300-600 <2.37 <1.78 IV:0.5-1.5 µg 2.5-5.0 µg Oral: 5 µg [33-66] Oral:0.5-1.5 µg IV: 2 µg 600-1000 < 2.37 <1.78 IV:1.0-3.0 µg 6.0-10 µg Oral: 5-10 µg [66-110] Oral:1-4 µg IV: 2-4 µg >1000 <2.50 < 1.78 IV:3.0-5.0 µg 10-15 µg Oral: 10-20 µg [110] Oral:3-7µg IV: 4-8 µg
  • 20. Guidelines for management of bone and mineral metabolism in CKD S17 11. Aluminum overload and toxicity in 12. Treatment of Aluminum Toxicity CKD 12.1 In all patients with baseline serum 11.1To prevent aluminum toxicity, the regular aluminum levels > 60 µg/L, a positive DFO administration of aluminum should be avoided test, or clinical symptoms consi-stent with and the dialysate concentration of aluminum aluminum toxicity, the source of aluminum should be maintained at<10 µg/L. should be identified and eliminated. 11.1a CKD patients ingesting aluminum 12.2 In symptomatic patients with serum should not receive citrate salts simulta- aluminum levels > 60 µg/L but < 200 µg/L or neously. a rise of aluminum after DFO >50 µg/L, DFO 11.2To assess aluminum exposure and the should be given to treat the aluminum risk of aluminum toxicity, serum alumi-num overload. levels should be measured at least yearly and 12.3To avoid DFO-induced neurotoxicity in every 3 months in those receiving aluminum- patients with serum aluminum >200 µg/L, DFO containing medications. should not be given until intensive dialysis (6 11.2a Baseline levels of serum aluminum days per week) with high-flux dialysis should be <20 µg/L. membrane and a dialysate alumi-num level of 11.3 A deferoxamine (DFO) test should be < 5 µg/L and until the pre-dialysis serum performed if there are elevated serum aluminum level has been reduced to <200 aluminum levels (60 to 200 µg/L); clinical µg/L. signs and symptoms of aluminum toxicity, or prior to parathyroid surgery if the 13. Treatment of Bone Disease in CKD 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 The therapeutic approach to bone disease session with a serum aluminum measured in CKD is based on its specific type i.e. before DFO infusion and 2 days later, high-turnover and mixed bone disease; before the next dialysis session. osteomalacia; and adynamic bone disease. 11.3b The test is considered positive if the increment of serum aluminum is > 50 13A. Hyperparathyroid (High-Turnover) µg/L. and mixed (High-Turnover with 11.3c A DFO test should not be performed Mineralization Defect) Bone Disease if the serum levels of aluminum are >200 µg/L to avoid DFO-induced 13A.1 In CKD patients who have plasma neurotoxicity. levels of intact PTH >70 pg/mL (7.7 11.4 The presence of aluminum bone disease pmol/L) in stage 3 or >110 pg/mL (12.1 can be predicted by a rise in serum pmol/L) in stage 4 on more than 2 aluminum of ≥ 50 µg/L following DFO consecutive measurements, dietary phos- challenge combined with plasma levels phate intake should be restricted. If this of intact PTH of < 150 pg/mL (16.5 is ineffective in lowering plasma PTH pmol/L). However, the gold standard for levels, calcitriol, or its analogs alfacal- the diagnosis of aluminum bone disease cidol or doxercalciferol, should be given is a bone biopsy showing increased to prevent or ameliorate bone disease. aluminum staining of the bone surface (> 13A.2 In CKD patients who have elevated 15% to 25%) using aluminum stain and plasma levels of intact PTH (>300 often adynamic bone or osteomalacia. 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
  • 21. S18 Guidelines for management of bone and mineral metabolism in CKD disease), and to treat defective mine- intact PTH >800 pg/mL [88.0 pmol/L]), ralization. associated with hypercalcemia and/or hyperphosphatemia that are refra-ctory to 13B. Osteomalacia medical therapy. 14.2Effective surgical therapy of severe 13B.1 Osteomalacia due to aluminum toxicity hyperparathyroidism can be accompli-shed should be prevented in dialysis patients by subtotal parathyroidectomy, or total by maintaining aluminum concentration parathyroidectomy with parathy-roid tissue in dialysate fluid at <10 µg/L and avoiding autotransplantation. the use of aluminum-containing compo- 14.3In patients who undergo parathyroid- unds (including sucralfate). ectomy the following should be done: 14.3a The blood level of ionized calcium 13B.2 Aluminum overload leading to aluminum should be measured every 4 to 6 bone disease should be treated with hours for the first 48 to 72 hours deferoxamine (DFO). after surgery, and then twice daily 13B.3 Osteomalacia due to vitamin D2 or D3 until stable. deficiency or phosphate depletion, though 14.3b If the blood levels of ionized or uncommon, should be treated with vita- corrected total calcium fall below min D2 or D3 supplementation and/or normal (<0.9 mmol/L or corres- phosphate administration, respectively. ponding to corrected total calcium 13B.3a If osteomalacia due to vitamin D of 1.8 mmol/L), a calcium gluconate deficiency fails to respond to ergo- infusion should be initiated at a rate calciferol or cholecalciferol, particu- of 1 to 2 mg elemental calcium per larly in patients with kidney failure kilogram body weight per hour and (Stage 5), treatment with an active adjusted to maintain an ionized vitamin D sterol may be given. calcium in the normal range (1.15 to 1.36 mmol/L). 13B.3b Doses of phosphate supplementation 14.3c The calcium infusion should be should be adjusted upwards until gradually reduced when the level of normal serum level of phosphorus is ionized calcium attains the normal achieved. range and remains stable. 14.3d When oral intake is possible, the 13C. Adynamic Bone Disease patient should receive calcium carbonate 1 to 2 g 3 times a day, as well as calcitriol of up to 2 µg/day, 13C.1 Adynamic bone disease in stage 5 CKD and these therapies should be (as determined either by bone biopsy or adjusted as necessary to maintain intact PTH <100 pg/ml [11.0 pmol/L]) the level of ionized calcium in the should be treated by allowing plasma normal range. levels of intact PTH to rise in order to 14.3e If the patient was receiving phos- increase bone turnover. phate binders prior to surgery, this 13C.la This can be accomplished by decreasing therapy may need to be disconti- doses of calcium-based phosphate binders nued or reduced as dictated by the and vitamin D or eliminating such therapy. levels of serum phosphorus, and some patients may require phosphate 14. Parathyroidectomy in patients with supplements. CKD 14.4 Imaging of parathyroid glands with"Tc- Sestamibi scan, ultrasound, CTscan, or 14.1Parathyroidectomy should bone and mineral metabolismshould be done prior to re- Guidelines for management of be recom- MRI in CKD S19 mended in patients with severe hyper- exploration parathyroid surgery. parathyroidism (persistent serum levels of 15. Metabolic Acidosis
  • 22. 16.2 During the first week after kidney 15.1In CKD Stages 3, 4 and 5, the serum transplantation, serum levels of phos- level of total CO2 should be measured. phorus should be measured daily. Kidney transplant recipients who develop persi- 15.1a The frequency of these measurements stently low levels of serum phosphate should be based on the stage of (<0.81 mmol/L) should be treated CKD, (Table 6). with phosphate supplementation. 16.3 To minimize bone mass loss and Table 6. Frequency for measurement of serum oste-onecrosis, the immunosuppressive levels of total Co2 regimen should be adjusted to the lowest CKD Stage GFR Range ml/ Frequency of effective dose of glucocorticoids. min/1.73m2 Measurement 16.4 Kidney transplant recipients should (At least) have bone mineral density (BMD) 3 30-59 every 12 measured by dual energy X-ray months absorptiometry (DEXA) to assess the 4 15-29 every 3 months presence or development of osteoporosis. 5 <15 every month 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 15.2In these patients, serum levels of total the time of the transplant or at CO2 should be maintained at > 22 mmol/L. If subsequent evaluations, therapy with necessary, supplemental alkali salts (such as parenteral amino-bisphosphonates NaHCo3 300-600 orally three times daily) should be considered. should be given to achieve this goal. 16.5 Treatment of disturbances in bone and mineral metabolism is deter- 16. Bone Disease in the Kidney mined by the level of kidney function Transplant Recipient in the transplant recipient. 16.1 Serum levels of calcium, phosphorus, Table 7. Frequency of measurement of calcium, total CO2 and plasma intact PTH should phosphorus, PTH and total CO2 after be monitored following kidney kidney transplantation transplant-tation. Parameter First 3 Months 3months to 1 16.1a The frequency of these measure- year ments should be based on the time Calcium Every 2 weeks Monthly following transplantation. Phosphorus Every 2 weeks Monthly PTH Monthly Every 3 months Total CO2 Every 2 weeks Monthly
  • 23. S20 Guidelines for management of bone and mineral metabolism in CKD References 1993;43:436-42 . 12. Slatopolsky E, Weerts C, Thielan J, Horst 1. Arnaud CD. Hyperparathyroidism and R, Harter H, Martin KJ. Marked renal failure. Kidney Int 1973;4:89-95. suppression of secondary hyperpara- 2. Bricker NS, Slatopolsky E, Reiss E, Avioli thyroidism by intravenous administration LV. Calcium, phosphorus, and bone in of 1,25-dihydroxy-cholecalciferol in renal disease and transplantation. Arch uremic patients. J Clin Invest 1984;7 Intern Med 1969;123:543-53. 4:2136-43. 3. Coburn JW, Elangovan L, Goodman WG, 13. Malluche H, Faugere MC. Renal bone Frazao JM. Calcium-sensing receptor and disease 1990. An unmet challenge for the calcimimetic agents. Kidney Int Suppl nephrologist. Kidney Int 1990;38:193-211. 1999;73:S52-8. 14. K/DOQI clinical practice guidelines for 4. De Marchi S, Cecchin E, Villalta D, chronic kidney disease: evaluation, Sepiacci G, Santini G, Bartoli E. Relief of classification, and stratification.Kidney pruritus and decreases in plasma histamine Disease Outcome Quality Initiative. Am concentrations during erythropoietin J Kidney Dis Suppl 1 2002;39:S1-S246. therapy in patients with uremia. N Engl J 15. Qi Q, Monier-Faugere MC, Geng Z, Med 1992;326:969-74. Malluche HH. Predictive value of serum 5. Fukagawa M. Cell biology of parathy- parathyroid hormone levels for bone roid hyperplasia in uremia. Am J Med turnover in patients on chronic mainte- Sci 1999;317:377-82. nance dialysis. Am J Kidney Dis 6. Llach F. Calcific uremic arteriolopathy 1995;26:622-31. (calciphylaxis): an evolving entity? Am 16. Block GA, Port FK. Reevaluation of J Kidney Dis 1998;32:514-8. risks associated with hyperphosphatemia 7. Llach F, Massry SG. On the mechanism and hyperparathyroidism in dialysis of secondary hyperparathyroidism in patients: recommendations for a change moderate renal insufficiency. J Clin in management. Am J Kidney Dis Endocrinol Metab 1985;61:601-6. 2000;35:1226-37. 8. Martin KJ, Gonzalez EA, Gellens M, 17. Ziolkowska H, Paniczyk-Tomaszewska Hamm LL, Abboud H, Lindberg J. 19- M, Debinski A, Polowiec Z, Sawicki A, Nor-l-aIpha-25-dihydroxy vitamin D2 Sieniawska M. Bone biopsy results and (Paricalcitol) safely and effectively reduces serum bone turnover parameters in the levels of intact parathyroid hormone in uremic children. Acta Paediatr 2000; patients on hemodialysis. J Am Soc 89:666-71. Nephrol 1998;9:1427-32. 18. Wang M, Hercz G, Sherrard DJ, 9. Massry SG, Coburn JW, Lee DB, Jowsey Maloney NA, Segre GV, Pei Y. J, Kleeman CR. Skeletal resistance to Relationship between intact 1-84 parathyroid hormone in renal failure. parathyroid hormone and bone Studies in 105 human subjects. Ann Intern histomorphometric parameters in dialysis Med 1973;78:357-64. patients without aluminum toxicity. Am J 10. Proudfoot D, Shanahan CM, Weissberg Kidney Dis 1995;26:836-44. PL: Vascular calcification: New insights 19. Solal ME, Sebert JL, Boudailliez B, et in-to an old problem. J Pathol al. Comparison of intact, midregion, and 1998;185:1-3 carboxy terminal assays of parathyroid 11. Sherrard DJ, Hercz G, Pei Y, et al. The hormone for the diagnosis of bone spectrum of bone disease in end-stage renal disease in hemo-dialyzed patients. J Clin failure - An evolving disorder. Kidney Int Endocrinol Metab 1991;73:516-24.
  • 24. 20. Hamdy NA, Kanis JA, Beneton MN, et Decreased 1,25- dihydroxyvitamin D3 GuidelinesEffect of alfacalcidol on natural metabolism in CKD al. for management of bone and mineral receptor density is associated with a S21 course of renal bone disease in mild to more severe form of parathyroid hyper- moderate renal failure. Br Med J 1995; plasia in chronic uremic patients. J Clin 310:358-63. Invest 1993;92:1436-43. 21. Goodman WG, Coburn JW. The use of 30. Ahmed S, O'Neill KD, Hood AF, Evan 1,25-dihydroxyvitamin D3 in early renal AP, Moe SM. Calciphylaxis is associa- failure. Annu Rev Med 1992 ;43:227-37. ted with hyperphosphatemia and incre- 22. Nordal KP, Dahl E. Low dose calcitriol ased osteopontin expression by vascular versus placebo in patients with predialysis smooth muscle cells. Am J Kidney Dis chronic renal failure. J Clin Endocrinol 2001;37:1267-76. Metab 1988;67:929-36. 31. Marchais SJ, Metivier F, Guerin AP, 23. Coen G, Mazzaferro S, Bonucci E, et al. London GM. Association of hyper- Treatment of secondary hyperparathy- phosphataemia with haemodynamic roidism of predialysis chronic renal failure disturbances in end-stage renal disease. with low doses of 1,25(OH)2D3: Humoral Nephrol Dial Transplant 1999;14:2178-83. and histomor-phometric results. Miner 32. Block GA, Hulbert-Shearon TE, Levin Electrolyte Metab 1986;12:375-82. NW, Port FK. Association of serum 24. Bianchi ML, Colantonio G, Campanini phosphorus and calcium X phosphate F, et al. Calcitriol and calcium carbonate product with mortality risk in chronic therapy in early chronic renal failure. hemodialysis patients: a national study. Nephrol Dial Transplant 1994;9:1595-99. Am J Kidney Dis 1998;31:607-17. 25. Portale AA, Booth BE, Halloran BP, 33. Massry SG, Coburn JW, Popovtzer MM, Morris RC Jr. Effect of dietary Shinaberger JH, Maxwell MH, Kleeman phosphorus on circulating concen- CR. Secondary hyperparathyroidism in trations of 1,25-dihydroxyvitamin D and chronic renal failure. The clinical immunoreactive parathyroid hormone in spectrum in uremia, during hemo- children with moderate renal insufficiency. dialysis, and after renal transplantation. J Clin Invest 1984;73:1580-89. Arch Intern Med 1969;124:431-41. 26. Silver J, Naveh-Many T, Mayer H, 34. Llach F, Massry SG, Singer FR, Schmelzer HJ, Popovtzer MM. Regula- Kurokawa K, Kaye JH, Coburn JW. tion by vitamin D metabolites of Skeletal resistance to endogenous parathyroid hormone gene transcription parathyroid hormone in patients with in vivo in the rat. J Clin Invest 1986; early renal failure. A possible cause for 78:1296-1301. secondary hyperparathyroidism. J Clin 27. Przedlacki J, Manelius J, Huttunen K. Endocrinol Metab 1975;41:339-45. Bone mineral density evaluated by dual- 35. Slatopolsky E, Finch J, Clay P, et al. A energy X-ray absorptiometry after one- novel mechanism for skeletal resistance year treatment with calcitriol started in in uremia. Kidney Int 2000;58:753-61. the predialysis phase of chronic renal 36. Silver J, Levi R. Cellular and molecular failure. Nephron 1995;69:433-7. mechanisms of secondary hyper-para- 28. Baker LR, Abrams L, Roe CJ, et al. thyroidism. Clin Nephrol 2005; 63(2): 1,25(OH)2D3 administration in mode- 119-26 rate renal failure: a prospective double- 37. Block GA, Port FK. Re-evaluation of blind trial. Kidney Int 1989;35:661-9. risks associated with hyperphosphatemia 29. Fukuda N, Tanaka H, Tominaga Y, and hyperparathyroidism in dialysis Fukagawa M, Kurokawa K, Seino Y. patients: recommendations for a change
  • 25. in management. Am J Kidney Dis phosphorus binders in patients on chronic 2000;35:1226-37. haemodialysis: a controlled study. Nephrol 38. Bleyer AJ, Burke SK, Dillon M, et al. A Dial Transplant 1993;8:341-6. S22 comparison of the calcium-free Guidelines for management of bone and mineral Nielsen HK, etCKD 46. Jespersen B, Jensen JD, metabolism in al. phosphate binder sevelamer hydro- Comparison of calcium carbonate and chloride with calcium acetate in the aluminium hydroxide phosphate binders on treatment of hyper-phosphatemia in biochemical bone markers, PTH(1-84), and hemodialysis patients. Am J Kidney Dis bone mineral content in dialysis patients. 1999;33:694-701. Nephrol Dial Transplant 1991;6:98-104. 39. Chertow GM, Burke SK, Lazarus JM, et 47. Silver J, Naveh-Many T, Mayer H, al. Poly [allylamine hydrochloride Schmelzer HJ, Popovtzer MM. Regulation (RenaGel). A noncalcemic phosphate by vitamin D metabolites of parathyroid binder for the treatment of hyperp- hormone gene transcription in vivo in the hosphatemia in chronic renal failure. Am J rat. J Clin Invest 1986;78.1296-301. Kidney Dis 1997;29:66-71. 48. Malluche HH, Faugere MC. Effects of 40. Chertow GM, Dillon M, Burke SK, et 1,25(OH)2D3 administration on bone in al. A randomized trial of sevelamer patients with renal failure. Kidney Int hydrochloride (RenaGel) with and without Suppl 1990;29:S48-53. supplemental calcium. Strategies for the 49. Coen G, Mazzaferro S, Bonucci E, et al. control of hyperphos-phatemia and Treatment of secondary hyper- hyper-parathyroidism in hemodialysis parathyroidism of predialysis chronic renal patients. Clin Nephrol 1999;51:18-26. failure with low doses of 1,25(OH)2D3: 41. Tessitore N, Venturi A, Adami S, et al. humoral and histomor-phometric results. Relationship between serum vitamin D Miner Electrolyte Metab 1986;12:375-82. metabolites and dietary intake of 50. Baker LR, Abrams L, Roe CJ, et al. phosphate in patients with early renal 1,25(OH)2D3 administration in moderate failure. Miner Electrolyte Metab renal failure: a prospective double-blind 1987;13:38-44. trial. Kidney Int 1989; 35:661-9. 42. Naveh-Many T, Rahamimov R, Livni N, 51. Langman CB, Bushinsky DA, Favus Silver J. Parathyroid cell proliferation in MJ, Coe FL. Ca and P regulation of normal and chronic renal failure rats. 1,25(OH)2D3 synthesis by vitamin D- The effects of calcium, phosphate, and replete rat tubules during acidosis. Am J vitamin D. J Clin Invest 1995;96:1786-93. Physiol 1986;251 :F911-8. 43. Better OS, Kleeman CR, Gonick HC, 52. Shiizaki K, Negi S, Hatamura I, et al. Varrady PD, Maxwell MH. Renal Biochemical and cellular effects of handling of calcium, magnesium and direct maxacalcitol injection into inorganic phosphate in chronic renal parathyroid gland in uremic rats. Am failure. Isr J Med Sci 1967;3:60-79. Soc Nephrol 2005; 16(1): 97-108. 44. van den Bergh JP, Gelens MA, Klaassen 53. Gerakis A, Hutchison AJ, Apostolou T, HA, Kaufmann BG, Bottger WM, Freemont AJ, Billis A. Biochemical Verstappen VM. Efficacy and tolerance of markers for non-invasive diagnosis of three different calcium acetate formu- hyperparathyroid bone disease and lations in hemodialysis patients. Neth J adynamic bone in patients on Med 1999;55:222-8. haemodialysis. Nephrol Dial Transplant 45. Ring T, Nielsen C, Andersen SP, Behrens 1996;11:2430-8. JK, Sodemann B, Kornerup HJ. Calcium 54. Hernandez D, Concepcion MT, Lorenzo acetate versus calcium carbonate as V, et al. Adynamic bone disease with
  • 26. negative aluminum staining in failure. Can J Ophthalmol 2004; predialysis patients: prevalence and 39(5):526-32. evolution after maintenance dialysis. 64. Rostand SG, Sanders C, Kirk KA, Nephrol Dial Transplant 1994;9:517-23. Rutsky EA, Eraser RG. Myocardial 55. Pei Y, Hercz G, Greenwood C, et al. calcification and cardiac dysfunction in Guidelines for management of bone and mineral metabolism in CKD Risk factors for renal osteodystrophy: a chronic renal failure. Am J Med S23 multivariant analysis. J Bone Miner Res 1988;85:651-7. 1995;10:149-56. 65. Chertow GM, Burke SK, Raggi P. 56. Hutchison AJ, Whitehouse RW, Sevelamer attenuates the progression of Freemont AJ, Adams JE, Mawer EB, coronary and aortic calcification in Gokal R. Histological, radiological, and hemodialysis patients. Kidney Int biochemical features of the adynamic 2002;62:245-52. bone lesion in continuous ambulatory 66. Maher ER, Young G, Smyth-Walsh B, peritoneal dialysis patients. Am J Nephrol Pugh S, Curtis JR. Aortic and mitral 1994;14:19-29. valve calcification in patients with end- 57. Kurz P, Monier-Faugere MC, Bognar B, stage renal disease. Lancet 1987;2:875-7. et al. Evidence for abnormal calcium 67. Fernandez-Reyes MJ, Auxiliadora Bajo homeostasis in patients with adynamic M, Robles P, et al. Mitral annular bone disease. Kidney Int 1994;46:855-61. calcification in CAPD patients with a low 58. Goodman WG, Ramirez JA, Belin TR, degree of hyperparathyroidism. An et al. Development of adynamic bone in analysis of other possible risk factors. patients with secondary hyperpara- Nephrol Dial Transplant 1995;10:2090-5. thyroidism after intermittent calcitriol 68. Valentzas C, Meindok H, Oreopoulos therapy. Kidney Int 1994;46:1160-6. DG, et al. Visceral calcification and Ca-P 59. Guerin AP, London GM, Marchais SJ, product. Adv Exp Med Biol 1978; Metivier F. Arterial stiffening and 103:187-93. vascular calcifications in end-stage renal 69. Ribeiro S, Ramos A, Brandao A, et al. disease. Nephrol Dial Transplant Cardiac valve calcification in haemo- 2000;15:1014-21. dialysis patients: Role of calcium- 60. Blacher J, Guerin AP, Pannier B, phosphate metabolism. Nephrol Dial Marchais SJ, London GM. Arterial Transplant1998;13:2037-40. calcifications, arterial stiffness, and 70. Alfrey AC. The role of abnormal cardiovascular risk in end-stage renal phosphorus metabolism in the progression disease. Hypertension 2001;38:938-42. of chronic kidney disease and metastatic 61. Jono S, McKee MD, Murry CE, et al. calcification. Kidney Int Suppl 2004;(90): Phosphate regulation of vascular smooth S13-7. muscle cell calcification. Circ Res 71. Touart DM, Sau P. Cutaneous 2000;87:E10-7. deposition diseases. Part II. J Am Acad 62. Canellos HM, Cooper J, Paek A, Chien J. Dermatol 1998; 39:527-44. Multiple calcified deposits along the 72. Headley CM, Wall B. ESRD-associated eyelid margins secondary to chronic renal cutaneous manifestations in a hemodia- failure and hyperparathyroidism. Opto- lysis population. Nephrol Nurs J 2002; metry 2005;76(3):181-4. 29(6): 525-7, 531-9. 63. Ozdemir M, Bakaris S, Ozdemir G, 73. Fulladosa X, Gonzales MT, Cruzado Buyukbese MA, Cetinkaya A. Ocular JM, et al. Metastatic calcifications in surface disorders and tear function severe secondary hyperparathyroidism: changes in patients with chronic renal evolution after renal transplantation.
  • 27. Transplant Proc 1995; 27:2272-6. J. Hyperparathyroidism after kidney trans- 74. Budisavljevic MN, Cheek D, Ploth DW. plantation: a retrospective case controlled Calciphylaxis in chronic renal failure. J study. Klin Wochenschr 1991;69:669-73. Am Soc Nephrol 1996;7:978-82. 85. Tominaga Y, Uchida K, Sato K, Numano 75. Tomson C. Vascular calcification in M, Tanaka Y, Takagi H. Parathyroidectomy chronic renal failure. Nephron Clin Pract before and after renal transplantation. 2003; 93(4): c124-30. Transplant Proc 1992;24:1861-2. 76. Guidelines 86. Guerin AP, London GM, Marchais SJ, S24 Reichel H, Deibert B, Schmidt-Gayk H,for management of bone and mineral metabolism in CKD Ritz E. Calcium metabolism in early Metivier F. Arterial stiffening and vascular chronic renal failure: Implications for calcifications in end-stage renal disease. the pathogenesis of hyperpara-thyroidism. Nephrol Dial Transplant 2000;15: 1014-21. Nephrol Dial Transplant 1991;6:162-9. 87. London GM, Guerin AP, Marchais SJ. 77. Hosking DJ, Chamberlain MJ. Calcium Arterial media calcification in end-stage balance in chronic renal failure. A study renal disease. impact on all-cause and using in vivo neutron activation cardiovascular mortality. Nephrol Dial analysis. Q J Med 1973;42:467-9. Transplant 2003;18:1731-40. 78. Cochran M, Bulusu L, Horsman A, 88. Souqiyyeh MZ, Alame H, Aswad S. Stasiak L, Nordin BE. Hypocalcaemia Calcium carbonate as a phosphate binder and bone disease in renal failure. in patients on regular hemodialysis: Riyadh Nephron1973;10:113-40. Central Hospital experience. Saudi Kidney 79. Goodman WG, Goldin J, Kuizon BD, et Dis Transplant Bull 1990;1(3):158-63. al. Coronary-artery calcifi-cation in young 89. Huraib S, Souqqiyeh MZ, Aswad S, al- adults with end-stage renal disease who Swailem AR. Pattern of renal are undergoing dialysis. N Engl J Med. osteodystrophy in hemodialysis patients in 2000; 342(20):1478-83. Saudi Arabia. Nephrol Dial Transplant. 80. Cozzolino M, Dusso AS, Liapis H, et al. 1993;8(7):603-8. The effects of sevelamer hydrochloride 90. Hussein MM, Mooij JM, Roujouleh H, and calcium carbonate on kidney el-Sayed H. Observations in a Saudi- calcification in uremic rats. J Am Soc Arabian dialysis population over a 13- Nephrol 2002;13: 2299-308. year period. Nephrol Dial Transplant. 81. Kostakis A, Vaiopoulos G, Kostanto- 1994;9(8):1072-6. poulos K, Za-vos G, Bocos I, Sgouromalis 91. George A, Paul TT, Kedharnath C, S. Parathyroidectomy in the treatment of Diwan M, Want MA, Mon H. Natural secondary hyperparathy-roidism in chronic Progression of Calciphylaxis in a Patient renal failure. Int Surg 1997;82:85-6. on Hemodialysis. Saudi J Kidney Dis 82. Gagne ER, Urena P, Leite-Silva S, et al. Transplant 1994;5(3):374-8. Short- and long-term efficacy of total 92. Rassoul Z, Mousa D, Rehman MA, et al parathyroidectomy with immediate auto- Serum parathyroid hormone suppression grafting compared with subtotal parathy- by intravenous 1,25-dihydroxyvitamin roidectomy in hemo-dialysis patients. J D3 in patients on maintenance haemo- Am Soc Nephrol 1992;3:1008-17. dialysis. Am J Nephrol 1995;15(6):507-11. 83. Fabretti F, Calabrese V, Fornasari V, 93. Souqiyyeh MZ, Huraib SO, Aswad S, Poletti I. Subtotal parathyroidectomy for Shaheen FA, Al-Swailem AR. Is secondary hyperparathyroidism in chronic aluminum related bone disease common renal failure. J Laryngol Otol 1991; in hemodialysis units using aluminum 105:562-7. based phosphate binders? Saudi J Kidney 84. Vlcek J, Binswanger U, Keusch G, Zaruba Dis Transplant 1995; 6(1):22-7.
  • 28. 94. Huraib S, Abu-Aisha H, Abed J, Al Dialysis Patients. Saudi J Kidney Dis Wakeel J, Al Desouki M, Memon N. Transplant 2000;11(2):174-80. Long-term effect of intravenous calcitriol 100.Ghacha R, Sinha AK, Karkar AM. on the treatment of severe hyperparathy- Spontaneous resolution of extensive roidism, parathyroid gland mass and bone periarticular metastatic calcification mineral density in hemodialysis patients. after renal transplant in a case of end Am J Nephrol 1997;17(2):118-23. stage renal disease. Ren Fail 2002; 95. al-Wakeel JS, Mitwalli AH, Huraib S, et al. 24(2): 239-44. Serum ionic fluoride levels in 101.Shaheen FA, Akeel NM, Badawi LS, Guidelines for management of bone and mineral metabolism in CKD haemodialysis and continuous ambulatory Souqiyyeh MZ. Efficacy and safety ofS25 peritoneal dialysis patients. Nephrol Dial sevelamer. Comparison with calcium Transplant 1997;12(7):1420-4. carbonate in the treatment of hyper- 96. Mitwalli AH. Spectrum of renal osteo- phosphatemia in hemodialysis patients. dystrophy in dialysis patients at a tertiary Saudi Med J 2004;25(6):785-91. hospital, Riyadh, Saudi Arabia. Saudi J 102. Souqiyyeh MZ, Shaheen FA. Attitude Kidney Dis Transplant 1998;9(2):128-33. of physicians towards the management 97. Al-Homrany M, Grillo IA, al-Ghamdi B, of bone disease in hemodialysis patients. el-Tahir M, Malatani TS, Khan MR. Saudi J Kidney Dis Transplant 2006; Diffuse pulmonary calcinosis and multiple 17(1):7-14. soft tissue calcification in renal failure patient with pathological femoral fracture. Indian J Chest Dis Allied Sci 1998; 40(3):205-11. 98. Huraib S, Tanimu D, Abu-Romeh S, et al. Effect of intravenous alfacalcidol on lymphocyte phenotyping in hemo-dialysis 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. patients. Am J Kidney Dis 1998; 32(6):1036-40. 99. Mitwalli AH, Alam AA. Intermittent Oral Versus Intravenous Alfacalcidol in