Efficacy of Sevelamer Carbonate for Hyperphosphatemia in Patients with End-stage Renal Disease: A Randomized Controlled Trial_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHAOHui ¹ , WANGJing-dong ² , ZHAODong-ming ³ , DONGYa-meng ³ ,  GAOYan ³

1. Weifang Medical University, Weifang 261053, China;
2. Qingdao Central Hospital, Qingdao 266044, China;
3. East District of Qingdao Municipal Hospital, Qingdao 266071, China;

Corresponding author：

GAOYan, Email: wjdwyd@163.com

Keywords：

Sevelamer carbonate; Hyperphosphataemia; End-stage renal disease; Calcium-phosphorus product; Randomized controlled trial

DOI：

10.7507/1672-2531.20140210

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the effectiveness and safety of sevelamer carbonate (Renvela) for hyperphosphatemia in patients with end-stage renal disease (ESRD). Methods ESRD patients undergoing renal replacement therapy with hyperphosphatemia in the East District of Qingdao Municipal Hospital from June to November 2013 were randomly divided into two groups. For eight-week treatment course, the trial group was treated with Renvela (initial dose of 800 mg, tid), and the control group was treated with calcium acetate (initial dose of 667 mg, tid). The dose was adjusted every two weeks to achieve serum phosphorus control. Serum levels of phosphorus, adjusted serum calcium, calcium-phosphorus products, intact parathyroid hormone (iPTH), low density lipoprotein cholesterol (LDL-C) and bicarbonate were recorded. Statistical analysis was conducted using SAS 8.2. Results A total of 68 ESRD patients were included, 34 patients in each group. After 8-week treatment, serum phosphorus and calcium-phosphorus products significantly decreased in both groups (P < 0.05). There was no significant difference between the Renvela group and the calcium acetate group in the achievement rate of serum phosphorus (43.33% vs. 36.67%), the incidence of hypercalcaemic events (6.67% vs. 13.33%), and the change of serum iPTH content (-0.88±10.34 pg/mL vs.-0.76±19.14 pg/mL), with no significant difference. However, the Renvela group showed significant advantages in the change of serum phosphorus content (-0.65±0.26 mmol/L vs.-0.53±0.22 mmol/L), the change of adjusted serum calcium content (0.01±0.05 vs. 0.09±0.06 mmol/L), the change of calcium-phosphorus products (-1.45±0.61 mmol²/L² vs.-0.97±0.47 mmol²/L2), the change of LDL-C content (-0.46±0.10 mmol/L vs. 0.02±0.12 mmol/L), and the change of serum bicarbonate content (-1.00±0.29 mmol/L vs. 0.01±0.18 mmol/L), with significant differences. There was no significant difference in the incidence of adverse reactions (14.71% vs. 11.76%) between the two groups (P=1.00), and the main adverse reaction was gastrointestinal reaction. Conclusion Renvela is relatively effective and safe for hyperphosphatemia in ESRD patients.

Citation： ZHAOHui, WANGJing-dong, ZHAODong-ming, DONGYa-meng, GAOYan. Efficacy of Sevelamer Carbonate for Hyperphosphatemia in Patients with End-stage Renal Disease: A Randomized Controlled Trial. Chinese Journal of Evidence-Based Medicine, 2014, 14(11): 1293-1298. doi: 10.7507/1672-2531.20140210 Copy

1.	Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease:results of the study to evaluate early kidney disease. Kidney Int, 2007, 71(1):31-38.
2.	Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol, 2004, 15(8):2208-2218.
3.	Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int, 2006, 70(4):771-780.
4.	Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis, 2001, 37(1 Suppl 2):S54-57.
5.	Prie D, Urena TP, Friedlander G. Latest findings in phosphate homeostasis. Kidney Int, 2009, 75(9):882-889.
6.	Block GA, Hulbert-Shearon TE, Levin NW, et al. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients:a national study. Am J Kidney Dis, 1998, 31(4):607-617.
7.	Lowrie EG, Lew NL. Death risk in hemodialysis patients:the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis, 1990, 15(5):458-482.
8.	Delmez JA, Slatopolsky E. Hyperphosphatemia:its consequences and treatment in patients with chronic renal disease. Am J Kidney Dis, 1992, 19(4):303-317.
9.	Navaneethan SD, Palmer SC, Craig JC, et al. Benefits and harms of phosphate binders in CKD:a systematic review of randomized controlled trials. Am J Kidney Dis, 2009, 54(4):619-637.
10.	Chen N, Wu X, Ding X, et al. Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients:a randomized, double-blind, placebo-controlled, dose-titration study. Nephrol Dial Transplant, 2014, 29(1):152-160.
11.	王莉, 李贵森, 刘志红.中华医学会肾脏病学分会《慢性肾脏病矿物质和骨异常诊治指导》.肾脏病与透析肾移植杂志, 2013, 22(6):554-559.
12.	Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis, 2001, 37(1 Suppl 2):S54-57.
13.	Mathew S, Tustison KS, Sugatani T, et al. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol, 2008, 19(6):1092-1105.
14.	Kestenbaum B, Sampson JN, Rudser KD, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol, 2005, 16(2):520-528.
15.	Voormolen N, Noordzij M, Grootendorst DC, et al. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant, 2007, 22(10):2909-2916.
16.	KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl, 2009, (113):S1-130.
17.	Martin KJ, Gonzalez EA. Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD:what is normal, when to start, and how to treat. Clin J Am Soc Nephrol, 2011, 6(2):440-446.
18.	Molony DA, Stephens BW. Derangements in phosphate metabolism in chronic kidney diseases/endstage renal disease:therapeutic considerations. Adv Chronic Kidney Dis, 2011, 18(2):120-131.
19.	Lin YF, Chien CT, Kan WC, et al. Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients:a randomized, open-label, parallel-group study. Clin Drug Investig, 2011, 31(4):257-267.
20.	Ketteler M, Rix M, Fan S, et al. Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol, 2008, 3(4):1125-1130.
21.	Block GA, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int, 2007, 71(5):438-441.
22.	Cassidy MJ, Owen JP, Ellis HA, et al. Renal osteodystrophy and metastatic calcification in long-term continuous ambulatory peritoneal dialysis. Q J Med, 1985, 54(213):29-48.
23.	Chertow GM, Burke SK, Lazarus JM, et al. Poly[allylamine hydrochloride] (RenaGel):a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis, 1997, 29(1):66-71.
24.	Kakuta T, Tanaka R, Hyodo T, et al. Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. Am J Kidney Dis, 2011, 57(3):422-431.
25.	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, 1999, 55(1):299-307.
26.	Koiwa F, Onoda N, Kato H, et al. Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan. Ther Apher Dial, 2005, 9(4):340-346.
27.	Braunlin W, Zhorov E, Guo A, et al. Bile acid binding to sevelamer HCl. Kidney Int, 2002, 62(2):611-619.
28.	Tschope W, Koch M, Thomas B, et al. Serum lipids predict cardiac death in diabetic patients on maintenance hemodialysis. Results of a prospective study. The German Study Group Diabetes and Uremia. Nephron, 1993, 64(3):354-358.
29.	Kraut JA. The role of metabolic acidosis in the pathogenesis of renal osteodystrophy. Adv Chronic Kidney Dis, 1995, 2(1):40-51.
30.	Kalantar-Zadeh K, Mehrotra R, Fouque D, et al. Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure. Semin Dial, 2004, 17(6):455-465.
31.	Szeto CC, Wong TY, Chow KM, et al. Oral sodium bicarbonate for the treatment of metabolic acidosis in peritoneal dialysis patients:a randomized placebo-control trial. J Am Soc Nephrol, 2003, 14(8):2119-2126.
32.	Iimori S, Mori Y, Akita W, et al. Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialyzed patients:a propensity-matched observational study. Clin Exp Nephrol, 2012, 16(6):930-937.
33.	Asmus HG, Braun J, Krause R, et al. Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrol Dial Transplant, 2005, 20(8):1653-1661.
34.	Lin YF, Chen YM, Hung KY, et al. Benefits of sevelamer on markers of bone turnover in Taiwanese hemodialysis patients. J Formos Med Assoc, 2010, 109(9):663-672.

1. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease:results of the study to evaluate early kidney disease. Kidney Int, 2007, 71(1):31-38.
2. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol, 2004, 15(8):2208-2218.
3. Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int, 2006, 70(4):771-780.
4. Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis, 2001, 37(1 Suppl 2):S54-57.
5. Prie D, Urena TP, Friedlander G. Latest findings in phosphate homeostasis. Kidney Int, 2009, 75(9):882-889.
6. Block GA, Hulbert-Shearon TE, Levin NW, et al. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients:a national study. Am J Kidney Dis, 1998, 31(4):607-617.
7. Lowrie EG, Lew NL. Death risk in hemodialysis patients:the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis, 1990, 15(5):458-482.
8. Delmez JA, Slatopolsky E. Hyperphosphatemia:its consequences and treatment in patients with chronic renal disease. Am J Kidney Dis, 1992, 19(4):303-317.
9. Navaneethan SD, Palmer SC, Craig JC, et al. Benefits and harms of phosphate binders in CKD:a systematic review of randomized controlled trials. Am J Kidney Dis, 2009, 54(4):619-637.
10. Chen N, Wu X, Ding X, et al. Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients:a randomized, double-blind, placebo-controlled, dose-titration study. Nephrol Dial Transplant, 2014, 29(1):152-160.
11. 王莉, 李贵森, 刘志红.中华医学会肾脏病学分会《慢性肾脏病矿物质和骨异常诊治指导》.肾脏病与透析肾移植杂志, 2013, 22(6):554-559.
12. Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis, 2001, 37(1 Suppl 2):S54-57.
13. Mathew S, Tustison KS, Sugatani T, et al. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol, 2008, 19(6):1092-1105.
14. Kestenbaum B, Sampson JN, Rudser KD, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol, 2005, 16(2):520-528.
15. Voormolen N, Noordzij M, Grootendorst DC, et al. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant, 2007, 22(10):2909-2916.
16. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl, 2009, (113):S1-130.
17. Martin KJ, Gonzalez EA. Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD:what is normal, when to start, and how to treat. Clin J Am Soc Nephrol, 2011, 6(2):440-446.
18. Molony DA, Stephens BW. Derangements in phosphate metabolism in chronic kidney diseases/endstage renal disease:therapeutic considerations. Adv Chronic Kidney Dis, 2011, 18(2):120-131.
19. Lin YF, Chien CT, Kan WC, et al. Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients:a randomized, open-label, parallel-group study. Clin Drug Investig, 2011, 31(4):257-267.
20. Ketteler M, Rix M, Fan S, et al. Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol, 2008, 3(4):1125-1130.
21. Block GA, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int, 2007, 71(5):438-441.
22. Cassidy MJ, Owen JP, Ellis HA, et al. Renal osteodystrophy and metastatic calcification in long-term continuous ambulatory peritoneal dialysis. Q J Med, 1985, 54(213):29-48.
23. Chertow GM, Burke SK, Lazarus JM, et al. Poly[allylamine hydrochloride] (RenaGel):a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis, 1997, 29(1):66-71.
24. Kakuta T, Tanaka R, Hyodo T, et al. Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. Am J Kidney Dis, 2011, 57(3):422-431.
25. 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, 1999, 55(1):299-307.
26. Koiwa F, Onoda N, Kato H, et al. Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan. Ther Apher Dial, 2005, 9(4):340-346.
27. Braunlin W, Zhorov E, Guo A, et al. Bile acid binding to sevelamer HCl. Kidney Int, 2002, 62(2):611-619.
28. Tschope W, Koch M, Thomas B, et al. Serum lipids predict cardiac death in diabetic patients on maintenance hemodialysis. Results of a prospective study. The German Study Group Diabetes and Uremia. Nephron, 1993, 64(3):354-358.
29. Kraut JA. The role of metabolic acidosis in the pathogenesis of renal osteodystrophy. Adv Chronic Kidney Dis, 1995, 2(1):40-51.
30. Kalantar-Zadeh K, Mehrotra R, Fouque D, et al. Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure. Semin Dial, 2004, 17(6):455-465.
31. Szeto CC, Wong TY, Chow KM, et al. Oral sodium bicarbonate for the treatment of metabolic acidosis in peritoneal dialysis patients:a randomized placebo-control trial. J Am Soc Nephrol, 2003, 14(8):2119-2126.
32. Iimori S, Mori Y, Akita W, et al. Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialyzed patients:a propensity-matched observational study. Clin Exp Nephrol, 2012, 16(6):930-937.
33. Asmus HG, Braun J, Krause R, et al. Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrol Dial Transplant, 2005, 20(8):1653-1661.
34. Lin YF, Chen YM, Hung KY, et al. Benefits of sevelamer on markers of bone turnover in Taiwanese hemodialysis patients. J Formos Med Assoc, 2010, 109(9):663-672.

Chinese Journal of Evidence-Based Medicine

Efficacy of Sevelamer Carbonate for Hyperphosphatemia in Patients with End-stage Renal Disease: A Randomized Controlled Trial

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