Jeerath Phannajit1,2,3, Natthaphon Wonghakaeo1, Kullaya Takkavatakarn1, Thanin Asawavichienjinda2, Kearkiat Praditpornsilpa1, Somchai Eiam-Ong1, Paweena Susantitaphong4,5. 1. Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand. 2. Division of Clinical Epidemiology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand. pesancerinus@hotmail.com. 5. Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. pesancerinus@hotmail.com.
Abstract
BACKGROUND: Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients. METHOD: A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables. RESULTS: This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed. CONCLUSIONS: In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
BACKGROUND: Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients. METHOD: A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables. RESULTS: This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed. CONCLUSIONS: In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
Authors: Yan Xie; Benjamin Bowe; Ali H Mokdad; Hong Xian; Yan Yan; Tingting Li; Geetha Maddukuri; Cheng-You Tsai; Tasheia Floyd; Ziyad Al-Aly Journal: Kidney Int Date: 2018-08-03 Impact factor: 10.612
Authors: Suetonia C Palmer; Sharon Gardner; Marcello Tonelli; Dimitris Mavridis; David W Johnson; Jonathan C Craig; Richard French; Marinella Ruospo; Giovanni F M Strippoli Journal: Am J Kidney Dis Date: 2016-07-22 Impact factor: 8.860
Authors: Steven Habbous; Sebastian Przech; Rey Acedillo; Sisira Sarma; Amit X Garg; Janet Martin Journal: Nephrol Dial Transplant Date: 2017-01-01 Impact factor: 5.992
Authors: Geoffrey A Block; Preston S Klassen; J Michael Lazarus; Norma Ofsthun; Edmund G Lowrie; Glenn M Chertow Journal: J Am Soc Nephrol Date: 2004-08 Impact factor: 10.121
Authors: Mark J Sarnak; Andrew S Levey; Anton C Schoolwerth; Josef Coresh; Bruce Culleton; L Lee Hamm; Peter A McCullough; Bertram L Kasiske; Ellie Kelepouris; Michael J Klag; Patrick Parfrey; Marc Pfeffer; Leopoldo Raij; David J Spinosa; Peter W Wilson Journal: Circulation Date: 2003-10-28 Impact factor: 29.690
Authors: Nigar Sekercioglu; Lehana Thabane; Juan Pablo Díaz Martínez; Gihad Nesrallah; Christopher J Longo; Jason W Busse; Noori Akhtar-Danesh; Arnav Agarwal; Reem Al-Khalifah; Alfonso Iorio; Gordon H Guyatt Journal: PLoS One Date: 2016-06-08 Impact factor: 3.240
Authors: Nigar Sekercioglu; Argie Angeliki Veroniki; Lehana Thabane; Jason W Busse; Noori Akhtar-Danesh; Alfonso Iorio; Luciane Cruz Lopes; Gordon H Guyatt Journal: PLoS One Date: 2017-03-01 Impact factor: 3.240