Citing observational and preclinical studies that link hyperphosphatemia to adverse clinical outcomes, current clinical practice guidelines recommend reduction of serum phosphate “towards the normal range” in patients with kidney failure undergoing hemodialysis. However, no randomized clinical trials have tested whether lowering serum phosphate improves clinical outcomes. HiLo is a pragmatic cluster-randomized clinical trial that will test the effects of targeting a ‘Hi’ or a ‘Lo’ serum phosphate (≥6.5 vs