- PURPOSE OF REVIEW: Phosphate lowering toward the normal range is advocated and widely practiced in patients with end-stage renal disease receiving dialysis. This approach is guided by basic science data and large observational studies that have demonstrated a consistent association between hyperphosphatemia and adverse events, including cardiovascular morbidity and all-cause mortality. There has never been a clinical trial to assess the efficacy of phosphate lowering in maintenance dialysis recipients. RECENT FINDINGS: Despite several trials comparing the effect of different phosphate-binding agents on biochemical targets, no trial has evaluated whether targeting normophosphatemia using phosphate binders mediates better patient outcomes. Recent work has highlighted the feasibility of conducting a randomized trial comparing two strategies for phosphate control. We believe that this research question is optimally suited to a pragmatic trial design. SUMMARY: There is a pressing need for a well-designed randomized controlled trial to evaluate whether intensive phosphate lowering confers improved cardiovascular outcomes in patients receiving maintenance dialysis. We propose a broad framework for such a trial using the principles of pragmatic trial design. The ultimate objective of such a trial will be to provide patients and clinicians with reliable and broadly applicable information on whether reducing serum phosphate toward the normal range improves patient-important outcomes.