Current opinion in nephrology and hypertension
May 15, 2026 · via Europe PMC
Novel therapeutic approaches for phosphate regulation.
Alzyood L, Chen W.
AI summary — for doctors, generated from the abstract only
This review (not an original study) summarizes recent developments in phosphate-lowering therapies for CKD, including new agents that reduce pill burden and more effectively lower phosphate than existing options, while noting that optimal serum phosphate targets remain undefined after a major trial was terminated early.
What was studied
The review summarizes recent clinical and experimental studies of phosphate-lowering therapies in CKD, including the HiLo trial testing different serum phosphate targets, and newer agents including oxylanthanum carbonate, tenapanor, and AP306 (EOS789), as well as synbiotic therapy's effects on intestinal phosphate absorption in an animal model. No new original patient data are presented by the review authors themselves.
Key findings
- The Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo trial) was terminated early and was underpowered, leaving the optimal serum phosphate target in hemodialysis patients still undefined.
- Oxylanthanum carbonate is described as a new lanthanum-based phosphate binder with equivalent efficacy to lanthanum carbonate but a smaller pill size.
- Tenapanor (a paracellular phosphate transport inhibitor) effectively lowers serum phosphate and reduces pill burden; AP306 (formerly EOS789), a transcellular phosphate transport inhibitor, lowers serum phosphate more effectively than sevelamer carbonate in cited studies.
- Gastrointestinal side effects are common with these newer phosphate-lowering agents, similar to existing phosphate binders; synbiotic therapy was shown to reduce intestinal phosphate absorption in rats with CKD, an early-stage finding.
Clinical relevance
This review may help nephrologists stay informed about newer, potentially more convenient (lower pill burden) phosphate-lowering options such as tenapanor and oxylanthanum carbonate, while recognizing that the mortality benefit of phosphate-lowering and optimal serum phosphate targets remain unresolved given the early termination of the HiLo trial.
Who should care
Limitations
Important limitations may not be assessable from the abstract alone, though the review itself notes the key HiLo trial was terminated early and underpowered, limiting conclusions about optimal phosphate targets; the synbiotic therapy finding is based on an animal (rat) model only.
This review highlights newer phosphate-lowering agents (tenapanor, oxylanthanum carbonate, AP306) that may reduce pill burden and improve phosphate control in CKD, while noting that optimal serum phosphate targets and mortality benefit remain unresolved after the HiLo trial was terminated early.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Purpose of review
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.
Recent findings
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.
Summary
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.
DOI
10.1097/mnh.0000000000001191
PMID
42130236
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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