Novel therapeutic approaches for phosphate regulation

Hyperphosphatemia in chronic kidney disease (CKD) is associated with vascular calcification and increased mortality. Despite widespread use of phosphate binders, treatment of hyperphosphatemia remains challenging and controversy persists regarding the optimal serum phosphate targets. This review summarizes recent clinical and experimental studies of phosphate-lowering therapies in CKD.

To define the optimal phosphate target, the Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) trial was conducted but was terminated early and underpowered. Oxylanthanum carbonate is a new lanthanum-based agent with phosphate-binding efficacy equivalent to lanthanum carbonate but smaller in pill size. Tenapanor, an inhibitor of paracellular phosphate transport, effectively lowers serum phosphate and reduces pill burden. AP306, formerly known as EOS789, an inhibitor of active transcellular phosphate transporters, lowers serum phosphate more effectively compared to sevelamer carbonate. As with existing phosphate binders, gastrointestinal side effects are common with these new phosphate-lowering agents. Lastly, synbiotic therapy modulates gut microbiota and reduces intestinal phosphate absorption in rats with CKD.

Combining phosphate binders with agents that inhibit paracellular and transcellular intestinal phosphate absorption may improve the treatment of hyperphosphatemia while reducing pill burden in CKD. Defining optimal serum phosphate targets and the mortality benefits of phosphate lowering is essential to minimize treatment-related adverse effects.