Leena Patel1, Lisa M Bernard1, Grahame J Elder2. 1. Cornerstone Research Group, Burlington, Ontario, Canada; 2. Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia; and Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia g.elder@garvan.org.au.
Abstract
BACKGROUND AND OBJECTIVES: People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines. RESULTS: We included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all-cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], -20.2 mg/dl; 95% CI, -25.9 to -14.5 mg/dl), LDL-cholesterol (MD, -21.6 mg/dl; 95% CI, -27.9 to -15.4 mg/dl), and calcium (MD, -0.4 mg/dl; 95% CI, -0.6 to -0.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences. CONCLUSIONS: Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis.
BACKGROUND AND OBJECTIVES:People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines. RESULTS: We included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all-cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], -20.2 mg/dl; 95% CI, -25.9 to -14.5 mg/dl), LDL-cholesterol (MD, -21.6 mg/dl; 95% CI, -27.9 to -15.4 mg/dl), and calcium (MD, -0.4 mg/dl; 95% CI, -0.6 to -0.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences. CONCLUSIONS:Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis.
Authors: Ana L E Cancela; Rodrigo B Oliveira; Fabiana G Graciolli; Luciene M dos Reis; Fellype Barreto; Daniela V Barreto; Lilian Cuppari; Vanda Jorgetti; Aluizio B Carvalho; Maria Eugênia Canziani; Rosa M A Moysés Journal: Nephron Clin Pract Date: 2010-08-04
Authors: A J Bleyer; S K Burke; M Dillon; B Garrett; K S Kant; D Lynch; S N Rahman; P Schoenfeld; I Teitelbaum; S Zeig; E Slatopolsky Journal: Am J Kidney Dis Date: 1999-04 Impact factor: 8.860
Authors: Paolo Raggi; George James; Steven K Burke; Jürgen Bommer; Scott Chasan-Taber; Herwig Holzer; Johan Braun; Glenn M Chertow Journal: J Bone Miner Res Date: 2004-12-20 Impact factor: 6.741
Authors: Emiliana Ferramosca; Steven Burke; Scott Chasan-Taber; Carlo Ratti; Glenn M Chertow; Paolo Raggi Journal: Am Heart J Date: 2005-05 Impact factor: 4.749
Authors: G M Chertow; M Dillon; S K Burke; M Steg; A J Bleyer; B N Garrett; D T Domoto; B M Wilkes; D G Wombolt; E Slatopolsky Journal: Clin Nephrol Date: 1999-01 Impact factor: 0.975
Authors: Wajeh Y Qunibi; Robert E Hootkins; Laveta L McDowell; Micah S Meyer; Matthias Simon; Rodolfo O Garza; Russell W Pelham; Mark V B Cleveland; Larry R Muenz; David Y He; Charles R Nolan Journal: Kidney Int Date: 2004-05 Impact factor: 10.612
Authors: Geoffrey A Block; David P Rosenbaum; Maria Leonsson-Zachrisson; Magnus Åstrand; Susanne Johansson; Mikael Knutsson; Anna Maria Langkilde; Glenn M Chertow Journal: J Am Soc Nephrol Date: 2017-02-03 Impact factor: 10.121
Authors: Sung Min Ko; Chao Zhang; Zhengjia Chen; Luis D'Marco; Antonio Bellasi; Arthur E Stillman; Geoffrey Block; Paolo Raggi Journal: J Nephrol Date: 2016-04-21 Impact factor: 3.902
Authors: Laura Sola; Nathan W Levin; David W Johnson; Roberto Pecoits-Filho; Harith M Aljubori; Yuqing Chen; Stefaan Claus; Allan Collins; Brett Cullis; John Feehally; Paul N Harden; Mohamed H Hassan; Fuad Ibhais; Kamyar Kalantar-Zadeh; Adeera Levin; Abdulkarim Saleh; Daneil Schneditz; Irma Tchokhonelidze; Rumeyza Turan Kazancioglu; Ahmed Twahir; Robert Walker; Anthony J O Were; Xueqing Yu; Fredric O Finkelstein Journal: Kidney Int Suppl (2011) Date: 2020-02-19
Authors: Annabel Biruete; Kathleen M Hill Gallant; Stephen R Lindemann; Gretchen N Wiese; Neal X Chen; Sharon M Moe Journal: J Ren Nutr Date: 2019-03-04 Impact factor: 3.655
Authors: Julia Spoendlin; Julie M Paik; T Tsacogianis; Seoyoung C Kim; Sebastian Schneeweiss; Rishi J Desai Journal: JAMA Intern Med Date: 2019-06-01 Impact factor: 21.873