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J Am Soc Nephrol 17: 11-15, 2006
© 2006 American Society of Nephrology

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Hemodialysis Clinical Practice Guidelines for the Canadian Society of Nephrology

CHAPTER 3: Mineral Metabolism

Kailash Jindal, Workgroup Chair, Christopher T. Chan, Clement Deziel, David Hirsch, Steven D. Soroka, Marcello Tonelli and Bruce F. Culleton, CPG Chair


   Management of Serum Phosphate, Serum Calcium, and Parathyroid Hormone
Top
 Management of Serum Phosphate,...
Recommendations for Research
 References
 
Recommendations

  1. Serum phosphate levels should be monitored and maintained within the normal range. (Grade C)
  2. To optimize control of serum phosphate, use restriction of dietary phosphate (Grade D), adjust the dialysis prescription (Grade D), and use oral phosphate binders. (Grade C)

Background
Elevated serum phosphate is common in individuals with stage 5 chronic kidney disease. Multiple studies have shown that elevated serum phosphate is associated with increased morbidity and mortality due to cardiovascular disease in the hemodialysis population (1–5). Increased serum phosphate is also involved in the pathogenesis of secondary hyperparathyroidism (6,7).

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) target level for serum phosphate levels (0.80 to 1.78 mmol/L) was partially based upon studies showing an association between cardiovascular disease morbidity and mortality and elevated serum phosphorus. In at least two of these studies, the association only reached significance at higher levels of serum phosphate (>2 mmol/L) (1,3). Decreasing phosphate levels toward the normal or target range might be associated with decreased mortality. However, to date, no randomized trials support this hypothesis.

To achieve an optimal phosphate level, the following strategies can be used:

  1. Restriction of dietary phosphate. A phosphorus intake of 800 to 1000 mg per day is recommended to help achieve serum phosphorus levels of 0.80 to 1.78 mmol/L. On an intake of 1000 mg per day, about 60 to 70% is absorbed. Dietary counseling has been shown to improve phosphate control in hemodialysis patients (8,9). Further research is warranted to ascertain whether phosphorus levels differ on a diet high in plant protein versus animal protein.
  2. Removal of phosphate by hemodialysis. Phosphate is mainly intracellular; therefore, clearance of phosphate during hemodialysis follows a pattern of most efficient clearance within the first 1 to 2 h with a plateau, and then rebounds within the first 4 h after the end of the treatment (10). The amount of phosphate removed is dependent also on the predialysis level. On average, about 900 to 1000 mg of phosphate can be removed per dialysis treatment. High-flux (versus low-flux) efficiency membranes may have higher phosphate clearances but phosphate removal is not significantly altered. Dialysis phosphate clearance may be improved by the use of frequent and longer dialysis, especially nocturnal hemodialysis (10,11).
  3. Use of phosphate binders. Given that most hemodialysis patients are in positive phosphate balance, there is a need to use phosphate binders to decrease phosphate absorption in the gut.

Because of the concern with aluminum toxicity, calcium-based binders continue to see extensive use. There has been increasing concern about the over-reliance of calcium-based phosphate binders due to the associated calcium load. Studies have found an association between daily calcium intake and coronary artery calcification (12–14) and calcification in other vascular beds (15). These data, plus extrapolation from studies of calcium balance and daily requirements, led the K/DOQI Mineral Metabolism Guideline Committee to recommend not exceeding the use of >1500 mg of elemental calcium in calcium-containing binders with a tolerable upper limit of 2500 mg for total calcium intake per day (16).

Despite the availability of several classes of phosphate binders, the majority of hemodialysis patients continue to have elevated phosphate levels (17,18). This illustrates the lack of efficacy of the available binders. When deciding on the choice and dose of binder(s) to use, it is important to realize that many of the clinical studies are of short duration (19–24), nonrandomized (20–22,25–31), open-label (19–22,25–28,30–38), or use no direct comparator (20–22,26–28,30,31,35). In addition, average medication doses or changes in laboratory parameters are not always reported, and adherence to binders ranges from 69 to 91%. As a result, available evidence does not allow the recommendation of one (or several) phosphate binders as superior to any other.

Recently, interest in the use of noncalcium-, nonaluminum-based binders has increased. Coronary artery calcification scores are lower in subjects treated with sevelamer compared with those treated with calcium binders (37). At the time of writing this guideline, only preliminary results were available from the Dialysis Clinical Outcomes Revisited (DCOR) trial. DCOR was a controlled clinical trial of approximately 2100 hemodialysis patients randomized to receive calcium-based phosphate binders or sevelamer. Three years after randomization, a 9% decrease in all-cause mortality (primary endpoint) was seen in those subjects assigned to sevelamer, although this did not reach statistical significance (P = 0.30) (39). Although subgroup analyses demonstrated that sevelamer use was associated with a reduction in mortality in subjects over 65 yr of age, interpretation of these data should await the final peer-reviewed publication. It should also be kept in mind that, compared with calcium-containing phosphate binders, use of sevelamer is no better at controlling serum phosphate and is associated with greater health care costs (23,40).

  1. Serum calcium levels should be monitored and maintained within the normal range. (Grade D)

Background
For the prevention of secondary hyperparathyroidism, individuals with kidney disease should have calcium levels maintained in the normal range defined by the testing laboratory. Although it is generally accepted that total serum calcium levels should be adjusted for serum albumin, Clase et al. found that total calcium had a higher correlation with the gold standard of ionized calcium measurement than many formulas (41).

Calcium-based phosphate binders contribute to the total daily calcium load in hemodialysis patients. Higher daily calcium intake is associated with poor outcomes including coronary calcification (13,14) and rapid progression of calcification in other vascular beds (42). Although several studies have reported an association between hypercalcemia and decreased survival (2,18,43), this finding is not consistent across all reports (1,44). Serum calcium is also inversely associated with intact parathyroid hormone (PTH) (44). In the setting of low PTH, suggesting low turnover bone disease, an increased calcium load cannot be incorporated into bone, and thus can precipitate into blood vessels, heart valves, and other soft tissues (45). Given that the above results and hypotheses are based upon associative data, may be confounded by vitamin D use, and have not been tested in controlled clinical trials, firm recommendations limiting the daily oral calcium intake cannot be made by this committee.

Dialysate calcium also impacts calcium balance. Fernandez et al. reported that the use of 1.25 mM dialysate calcium resulted in negative calcium balance, despite no change in serum ionized calcium values (46). However, compared with 1.75 mM dialysate calcium, 1.25 mM dialysate calcium led to higher parathyroid hormone levels and greater use of vitamin D.

  1. Measure PTH levels on a regular basis (at a minimum every 4 mo) (Grade D, opinion) and direct therapy to avoid both high and low PTH levels. (Grade C)
  2. Give priority to phosphate and calcium targets over the management of PTH. (Grade D, opinion)
  3. Avoid intach PTH (iPTH) levels below 100 pg/ml (10.6 pmol/L) (Grade C); iPTH levels >500 pg/ml (53 pmol/L) should be treated if accompanied by symptoms or clinical signs of hyperparathyroidism. (Grade D, opinion)
  4. Vitamin D sterols can be used in the treatment of secondary hyperparathyroidism, but should be discontinued when PTH levels decrease below target levels, or if calcium or phosphate levels increase above target levels. (Grade C)
  5. Parathyroidectomy should be considered for those patients who have failed standard treatments and have persistently elevated PTH levels with systemic complications. (Grade D, opinion)

Background
Given that PTH is a major regulator of bone turnover and skeletal cellular activity, PTH is widely used as a surrogate marker instead of bone histomorphometric analysis (the gold standard). Recently, many questions have been raised about the method of PTH measurement, the normal or optimal range of the PTH level, and the correlation of PTH levels with bone histology. The principal method of measurement of PTH over the last couple decades has been a two-site immunometric technique called the "intact" PTH (iPTH) assay. This form of measurement has been widely used and is the basis of current classification schemes for bone turnover. It is now known that assays measuring iPTH also measure a large PTH fragment (PTH 7 to 84). This has led to assays specific for PTH 1 to 84 (biointact or whole PTH assays). Although these new assays appear promising, much of the data with renal bone disease and the correlation with PTH levels exist for iPTH measurements. On this basis, the current guidelines use target levels based upon the iPTH assay. Users of these guidelines are instructed to determine the assay used locally and use sound clinical judgment if the biointact or whole PTH assay is used.

Much of the research that correlates iPTH values to bone biopsy findings was done at least 10 yr ago, where iPTH levels <165 pg/ml (17.5 pmol/L) were associated with adynamic bone disease (low turnover disease) and iPTH levels >300 pg/ml (31.8 pmol/L) correlated with high turnover bone disease (47–49). However, it has also been shown that use of calcitriol modifies the relationship between iPTH and indices of bone formation and turnover (50).

Coen et al. used receiver-operator characteristic (ROC) curves to determine that a cutoff value of 210 pg/ml (22.3 pmol/L) for iPTH had a positive predictive value of 100 and a negative predictive value of 45 in predicting adynamic bone disease versus mixed osteodystrophy or high turnover disease (51). In the K/DOQI bone metabolism guidelines, summary ROC curves from 5 individual studies revealed that a threshold iPTH level of 150 to 200 pg/ml (15.9 to 21.2 pmol/L) had a sensitivity of 93% and specificity of 77% for diagnosis of high turnover bone disease, while a PTH value of 60 pg/ml (6.4 pmol/L) or less had a sensitivity of 70% and specificity of 87% for low bone turnover (16).

Controlling or preventing secondary hyperparathyroidism is important in patients with chronic kidney disease. Not only is there concern about renal bone disease, but also increasingly there is concern about other systemic toxicities. Several studies have shown that moderate to severe elevations of iPTH are associated with increased morbidity and mortality (1–3). In addition, decreased iPTH levels are also associated with increased morbidity and mortality (4,44,52). Therefore, iPTH values both above and below the current target range are undesirable.

Specific treatment strategies include maintaining normal calcium and phosphate levels. Calcium supplementation may also be needed to maintain serum calcium with the normal range. Vitamin D analogs 1{alpha}(OH)D3 or 1,25(OH)2D3 are used to treat patients with elevated PTH levels as they act by suppressing prepro-PTH-mRNA in the parathyroid cell. Vitamin D analogs can be prescribed daily or intermittently, orally or intravenously. Clinical trials have been inconclusive in determining the best route of administration (53–55). Intravenous therapy after dialysis is an effective way to ensure compliance. All vitamin D analogues have the ability to increase serum levels of calcium and phosphate, and although this effect may be less with newer analogues, valid studies with relevant clinical outcomes are not available (5,56–63).

Parathyroidectomy is used for secondary hyperparathyroidism that is not controlled by standard medical therapy, and is associated with other clinical indications, such as elevated serum calcium or phosphate, tendon rupture, resistant anemia, or bone pain. A recent analysis of US Renal Data System data shows that although mortality is higher for the first 3 mo after parathyroidectomy, a survival advantage is apparent 20 mo postoperatively (64).

A calcimimetic agent, specifically cinacalcet, has recently been released for the treatment of secondary hyperparathyroidism in dialysis patients. Cinacalcet binds to the calcium-sensing receptor on the PTH gland cells and increases the sensitivity of the receptor to calcium. The largest study published confirmed that subjects treated with cinacalcet had a therapeutic response, with 43% achieving an iPTH level of <250 pg/ml (26.5 pmol/L) as compared with only 5% in the control group (65). The decrease in iPTH was seen at all levels of baseline iPTH. Additional benefits seen were significant decreases in serum phosphate, calcium and calcium x phosphorus product. Hypocalcemia can occur, but can be minimized by dose titration plus the addition of vitamin D analogues to maintain a normal serum calcium level. All the published studies with cinacalcet have been of relatively short duration, using the surrogate endpoints of iPTH, phosphate, and calcium. Longer-term use will be needed to determine the impact on use of phosphate binders, calcium supplements, and vitamin D analogues, and perhaps more importantly the impact of decreasing iPTH on morbidity and mortality.


   Recommendations for Research
Top
 Management of Serum Phosphate,...
 Recommendations for Research
References
 

  1. Although many studies have shown that elevated phosphate, calcium, and iPTH are associated with increased morbidity and mortality, prospective randomized studies are needed to determine whether achieving suggested targets for calcium and phosphate decreases mortality in hemodialysis patients.
  2. Studies are needed to determine the appropriate target range of PTH (intact or whole assays) for normal bone metabolism in stage 5 chronic kidney disease patients on dialysis.
  3. Evaluate the impact vitamin D sterols and calcimimetics on morbidity and mortality in hemodialysis patients.


   References
Top
 Management of Serum Phosphate,...
 Recommendations for Research
 References
 

  1. Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis 31 : 607 –617, 1998[Medline]
  2. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15 : 2208 –2218, 2004[Abstract/Free Full Text]
  3. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12 : 2131 –2138, 2001[Abstract/Free Full Text]
  4. Stevens LA, Djurdjev O, Cardew S, Cameron EC, Levin A: Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: Evidence for the complexity of the association between mineral metabolism and outcomes. J Am Soc Nephrol 15 : 770 –779, 2004[Abstract/Free Full Text]
  5. Slinin Y, Foley RN, Collins AJ: Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: The USRDS Waves 1, 3, and 4 study. J Am Soc Nephrol 16 : 1788 –1793, 2005[Abstract/Free Full Text]
  6. Drueke TB: Cell biology of parathyroid gland hyperplasia in chronic renal failure. J Am Soc Nephrol 11 : 1141 –1152, 2000[Free Full Text]
  7. Jorna FH, Tobe TJ, Huisman RM, de Jong PE, Plukker JT, Stegeman CA: Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy. Nephrol Dial Transplant 19 : 1168 –1173, 2004[Abstract/Free Full Text]
  8. Ashurst IB, Dobbie H: A randomized controlled trial of an educational intervention to improve phosphate levels in hemodialysis patients. J Ren Nutr 13 : 267 –274, 2003[CrossRef][Medline]
  9. Shaw-Stuart NJ, Stuart A: The effect of an educational patient compliance program on serum phosphate levels in patients receiving hemodialysis. J Ren Nutr 10 : 80 –84, 2000[Medline]
  10. Mucsi I, Hercz G, Uldall R, Ouwendyk M, Francoeur R, Pierratos A: Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis. Kidney Int 53 : 1399 –1404, 1998[CrossRef][Medline]
  11. Lindsay RM, Alhejaili F, Nesrallah G, Leitch R, Clement L, Heidenheim AP, Kortas C: Calcium and phosphate balance with quotidian hemodialysis. Am J Kidney Dis 42 : 24 –29, 2003[CrossRef][Medline]
  12. Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, Chertow GM: Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 39 : 695 –701, 2002[Abstract/Free Full Text]
  13. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342 : 1478 –1483, 2000[Abstract/Free Full Text]
  14. Moe SM, O’Neill KD, Fineberg N, Persohn S, Ahmed S, Garrett P, Meyer CA: Assessment of vascular calcification in ESRD patients using spiral CT. Nephrol Dial Transplant 18 : 1152 –1158, 2003[Abstract/Free Full Text]
  15. Guerin AP, London GM, Marchais SJ, Metivier F: Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 15 : 1014 –1021, 2000[Abstract/Free Full Text]
  16. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42 : S1 –S201, 2003[Medline]
  17. Moe SM, Chertow GM, Coburn JW, Quarles LD, Goodman WG, Block GA, Drueke TB, Cunningham J, Sherrard DJ, McCary LC, Olson KA, Turner SA, Martin KJ: Achieving NKF-K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int 67 : 760 –771, 2005[CrossRef][Medline]
  18. Young EW, Albert JM, Satayathum S, Goodkin DA, Pisoni RL, Akiba T, Akizawa T, Kurokawa K, Bommer J, Piera L, Port FK: Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study. Kidney Int 67 : 1179 –1187, 2005[CrossRef][Medline]
  19. Pflanz S, Henderson IS, McElduff N, Jones MC: Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis. Nephrol Dial Transplant 9 : 1121 –1124, 1994[Abstract/Free Full Text]
  20. Goldberg DI, Dillon MA, Slatopolsky EA, Garrett B, Gray JR, Marbury T, Weinberg M, Wombolt D, Burke SK: Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients. Nephrol Dial Transplant 13 : 2303 –2310, 1998[Abstract/Free Full Text]
  21. Slatopolsky EA, Burke SK, Dillon MA: RenaGel, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. The RenaGel Study Group. Kidney Int 55 : 299 –307, 1999[CrossRef][Medline]
  22. Hutchison AJ, Speake M, Al-Baaj F: Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: A 4-week, dose-finding, open-label study with lanthanum carbonate. Nephrol Dial Transplant 19 : 1902 –1906, 2004[Abstract/Free Full Text]
  23. Qunibi WY, Hootkins RE, McDowell LL, Meyer MS, Simon M, Garza RO, Pelham RW, Cleveland MV, Muenz LR, He DY, Nolan CR: Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study). Kidney Int 65 : 1914 –1926, 2004[CrossRef][Medline]
  24. Ring T, Nielsen C, Andersen SP, Behrens JK, Sodemann B, Kornerup HJ: Calcium acetate versus calcium carbonate as phosphorus binders in patients on chronic haemodialysis: A controlled study. Nephrol Dial Transplant 8 : 341 –346, 1993[Abstract/Free Full Text]
  25. Williams B, Vennegoor M, O’Nunan T, Walls J: The use of calcium carbonate to treat the hyperphosphataemia of chronic renal failure. Nephrol Dial Transplant 4 : 725 –729, 1989[Abstract/Free Full Text]
  26. Chertow GM, Burke SK, Dillon MA, Slatopolsky E: Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant 14 : 2907 –2914, 1999[Abstract/Free Full Text]
  27. Takahashi Y, Tanaka A, Nakamura T, Fukuwatari T, Shibata K, Shimada N, Ebihara I, Koide H: Nicotinamide suppresses hyperphosphatemia in hemodialysis patients. Kidney Int 65 : 1099 –1104, 2004[CrossRef][Medline]
  28. Sturtevant JM, Hawley CM, Reiger K, Johnson DW, Campbell SB, Burke JR, Bofinger A, Isbel NM: Efficacy and side-effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders. Nephrology (Carlton) 9 : 406 –413, 2004[Medline]
  29. Slatopolsky E, Weerts C, Lopez-Hilker S, Norwood K, Zink M, Windus D, Delmez J: Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 315 : 157 –161, 1986[Abstract]
  30. Moriniere P, Vinatier I, Westeel PF, Cohemsolal M, Belbrik S, Abdulmassih Z, Hocine C, Marie A, Leflon P, Roche D, et al.: Magnesium hydroxide as a complementary aluminium-free phosphate binder to moderate doses of oral calcium in uraemic patients on chronic haemodialysis: Lack of deleterious effect on bone mineralisation. Nephrol Dial Transplant 3 : 651 –656, 1988[Abstract/Free Full Text]
  31. Guillot AP, Hood VL, Runge CF, Gennari FJ: The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis. Nephron 30 : 114 –117, 1982[Medline]
  32. Bleyer AJ, Burke SK, Dillon M, Garrett B, Kant KS, Lynch D, Rahman SN, Schoenfeld P, Teitelbaum I, Zeig S, Slatopolsky E: A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am J Kidney Dis 33 : 694 –701, 1999[Medline]
  33. Yang WC, Yang CS, Hou CC, Wu TH, Young EW, Hsu CH: An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: Ferric citrate. Nephrol Dial Transplant 17 : 265 –270, 2002[Abstract/Free Full Text]
  34. Janssen MJ, van der KA, ter Wee PM, van Boven WP: Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients. Clin Nephrol 45 : 111 –119, 1996[Medline]
  35. Hercz G, Kraut JA, Andress DA, Howard N, Roberts C, Shinaberger JH, Sherrard DJ, Coburn JW: Use of calcium carbonate as a phosphate binder in dialysis patients. Miner Electrolyte Metab 12 : 314 –319, 1986[Medline]
  36. Caravaca F, Santos I, Cubero JJ, Esparrago JF, Arrobas M, Pizarro JL, Robles R, Sanchez-Casado E: Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients. Nephron 60 : 423 –427, 1992[Medline]
  37. Chertow GM, Burke SK, Raggi P: Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62 : 245 –252, 2002[CrossRef][Medline]
  38. Delmez JA, Kelber J, Norword KY, Giles KS, Slatopolsky E: Magnesium carbonate as a phosphorus binder: A prospective, controlled, crossover study. Kidney Int 49 : 163 –167, 1996[Medline]
  39. Long term use of renagel results in lower rates of death. Available online at www.genzyme.com/corp/investors/GENZ%20PR-072805.asp. Accessed August 21, 2005
  40. Manns B, Stevens L, Miskulin D, Owen WF Jr, Winkelmayer WC, Tonelli M: A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States. Kidney Int 66 : 1239 –1247, 2004[CrossRef][Medline]
  41. Clase CM, Norman GL, Beecroft ML, Churchill DN: Albumin-corrected calcium and ionized calcium in stable haemodialysis patients. Nephrol Dial Transplant 15 : 1841 –1846, 2000[Abstract/Free Full Text]
  42. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, Nihei H: The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis 42 : 303 –309, 2003[CrossRef][Medline]
  43. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R: Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 349 : 446 –456, 2003[Abstract/Free Full Text]
  44. Guh JY, Chen HC, Chuang HY, Huang SC, Chien LC, Lai YH: Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients. Am J Kidney Dis 39 : 1245 –1254, 2002[CrossRef][Medline]
  45. Kurz P, Monier-Faugere MC, Bognar B, Werner E, Roth P, Vlachojannis J, Malluche HH: Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int 46 : 855 –861, 1994[Medline]
  46. Fernandez E, Borras M, Pais B, Montoliu J: Low-calcium dialysate stimulates parathormone secretion and its long-term use worsens secondary hyperparathyroidism. J Am Soc Nephrol 6 : 132 –135, 1995[Abstract]
  47. Hercz G, Pei Y, Greenwood C, Manuel A, Saiphoo C, Goodman WG, Segre GV, Fenton S, Sherrard DJ: Aplastic osteodystrophy without aluminum: The role of "suppressed" parathyroid function. Kidney Int 44 : 860 –866, 1993[Medline]
  48. Quarles LD, Lobaugh B, Murphy G: Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 75 : 145 –150, 1992[Abstract]
  49. Salusky IB, Ramirez JA, Oppenheim W, Gales B, Segre GV, Goodman WG: Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int 45 : 253 –258, 1994[Medline]
  50. Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB: Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 46 : 1160 –1166, 1994[Medline]
  51. Coen G, Bonucci E, Ballanti P, Balducci A, Calabria S, Nicolai GA, Fischer MS, Lifrieri F, Manni M, Morosetti M, Moscaritolo E, Sardella D: PTH 1–84 and PTH "7–84" in the noninvasive diagnosis of renal bone disease. Am J Kidney Dis 40 : 348 –354, 2002[CrossRef][Medline]
  52. Avram MM, Mittman N, Myint MM, Fein P: Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation. Am J Kidney Dis 38 : 1351 –1357, 2001[Medline]
  53. Quarles LD, Yohay DA, Carroll BA, Spritzer CE, Minda SA, Bartholomay D, Lobaugh BA: Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney Int 45 : 1710 –1721, 1994[Medline]
  54. Fischer ER, Harris DC: Comparison of intermittent oral and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism. Clin Nephrol 40 : 216 –220, 1993[Medline]
  55. Indridason OS, Quarles LD: Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group. Kidney Int 57 : 282 –292, 2000[CrossRef][Medline]
  56. Dobrez DG, Mathes A, Amdahl M, Marx SE, Melnick JZ, Sprague SM: Paricalcitol-treated patients experience improved hospitalization outcomes compared with calcitriol-treated patients in real-world clinical settings. Nephrol Dial Transplant 19 : 1174 –1181, 2004[Abstract/Free Full Text]
  57. Akiba T, Marumo F, Owada A, Kurihara S, Inoue A, Chida Y, Ando R, Shinoda T, Ishida Y, Ohashi Y: Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 32 : 238 –246, 1998[Medline]
  58. Hayashi M, Tsuchiya Y, Itaya Y, Takenaka T, Kobayashi K, Yoshizawa M, Nakamura R, Monkawa T, Ichihara A: Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: A randomized prospective multicentre trial. Nephrol Dial Transplant 19 : 2067 –2073, 2004[Abstract/Free Full Text]
  59. Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D: Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 63 : 1483 –1490, 2003[CrossRef][Medline]
  60. Maung HM, Elangovan L, Frazao JM, Bower JD, Kelley BJ, Acchiardo SR, Rodriguez HJ, Norris KC, Sigala JF, Rutkowski M, Robertson JA, Goodman WG, Levine BS, Chesney RW, Mazess RB, Kyllo DM, Douglass LL, Bishop CW, Coburn JW: Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: A sequential comparison. Am J Kidney Dis 37 : 532 –543, 2001[Medline]
  61. Frazao JM, Elangovan L, Maung HM, Chesney RW, Acchiardo SR, Bower JD, Kelley BJ, Rodriguez HJ, Norris KC, Robertson JA, Levine BS, Goodman WG, Gentile D, Mazess RB, Kyllo DM, Douglass LL, Bishop CW, Coburn JW: Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism. Am J Kidney Dis 36 : 550 –561, 2000[Medline]
  62. Martin KJ, Gonzalez EA, Gellens M, Hamm LL, Abboud H, Lindberg J: 19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 9 : 1427 –1432, 1998[Abstract]
  63. Llach F, Yudd M: Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism. Am J Kidney Dis 38[Suppl 5] : S45 –S50, 2001
  64. Kestenbaum B, Andress DL, Schwartz SM, Gillen DL, Seliger SL, Jadav PR, Sherrard DJ, Stehman-Breen C: Survival following parathyroidectomy among United States dialysis patients. Kidney Int 66 : 2010 –2016, 2004[CrossRef][Medline]
  65. Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, Hercz G, Cunningham J, bu-Alfa AK, Messa P, Coyne DW, Locatelli F, Cohen RM, Evenepoel P, Moe SM, Fournier A, Braun J, McCary LC, Zani VJ, Olson KA, Drueke TB, Goodman WG: Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350 : 1516 –1525, 2004[Abstract/Free Full Text]




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