Effects of phosphorus-restricted diet and phosphate-binding therapy on outcomes in patients with chronic kidney disease

BACKGROUND: Phosphorus is associated with mortality in patients with chronic kidney disease (CKD) not on dialysis, possibly through phosphorus-dependent vascular calcification. Although a phosphorus-restricted diet reduces serum phosphorus, it is unlikely that it reduces vascular calcification progression in CKD. This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of all-cause mortality and/or dialysis initiation by attenuating coronary artery calcification (CAC) progression in non-dialysis CKD patients. METHODS: This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD. Patients (n = 113) with stage 3-4 CKD and evidence of CAC on a phosphorus-restricted diet were randomized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet. End-points were death for any cause and initiation of dialysis. Patients were monitored to the first event or to conclusion of the 36-month follow-up. RESULTS: Overall, treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality, dialysis initiation, and the composite end-point. After adjustment for confounders, sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate. Accelerated progression (annual CAC increase >75th percentile of the study cohort) increased the risk of all-cause mortality and composite end-point (p = 0.01) independently of the use of sevelamer. CONCLUSIONS: A significant reduction in all-cause mortality, dialysis initiation, and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression. Future studies should investigate the role of serum phosphorus, the usefulness of a phosphorus-restricted diet, and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients