Efficacy And Safety Of Phosphate Binders For Hyperphosphatemia In Maintenance Hemodialysis Patients:a Systematic Review And Bayesian Network Meta-analysis

Objective:Hyperphosphatemia is one of the most common complications of end-stage renal disease, which can cause secondary hyperparathyroidism, bone diseases, and cardiovascular calcification. Hyperphosphatemia is also associated with increased mortality and reduced quality of life of dialysis patients. Phosphate binders are widely used to control serum phosphorus levels in ESRD patients. Currently, calcium carbonate, calcium acetate, sevelamer, and lanthanum carbonate are four popular phosphate binders. The objective of this study is to evaluate the efficacy and safety of these four different phosphate binders for the treatment of hyperphosphatemia in ESRD patients.Methods:Three major database, including Pubmed, ISI Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL), are searched for randomized controlled trials published before December2013, comparing at least two of calcium carbonate, calcium acetate, sevelamer, lanthanum carbonate and placebo in patients on maintenance hemodialysis. The primary outcomes are serum phosphorus, calcium, calcium x phosphate product (CaxP), parathyroid hormone levels and the incidence of hypercalcemia. Bayesian network meta-analysis which combines direct and indirect evidence is used to estimate the relative effects among these five treatments and the probabilities of ranking for each treatment.Results:Twenty-five trials (3,111patients) were included in this systemic review. Calcium carbonate, calcium acetate, sevelamer and lanthanum carbonate showed no evident difference in affecting the change of serum phosphorus, CaxP and parathyroid hormone levels. In contrast to calcium carbonate and calcium acetate, sevelamer and lanthanum carbonate had no significant influence on the change of serum calcium. Compared with calcium carbonate and calcium acetate, the incidence of hypercalcemia is much lower in treatments using sevelamer or lanthanum carbonate. Existing data are insufficient to conduct a network meta-analysis of the effects of these four phosphate binders on mortality or other patient-level outcomes.Conclusion:Non-calcareous phosphate binders (lanthanum carbonate and sevelamer) are effective and riskless in treating hyperphosphatemia patients in hemodialysis. Compared with the calcareous phosphate binders, lanthanum carbonate and sevelamer can reduce the incidence of hypercalcium. Additional large randomized, double blinded clinical trials are still required to investigate the effects of different phosphate binders on mortality or other patient-level outcomes.