Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients.

BACKGROUND: Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. METHODS: Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. RESULTS: In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. CONCLUSIONS: FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.

Phosphate Absorption and Hyperphosphatemia Management in Kidney Disease: A Physiology-Based Review.

Phosphate absorption occurs in the gastrointestinal tract through paracellular absorption and transcellular transport. The paracellular pathway does not saturate and has a significantly higher absorption capacity than does the transcellular pathway. Evidence indicates that this pathway is the primary mechanism of intestinal phosphate absorption, particularly with Western diets containing high amounts of phosphorus. Elevated serum phosphorus concentrations are associated with cardiovascular morbidity and mortality but serum phosphorus concentrations > 5.5 mg/dL are highly prevalent despite best efforts with dietary phosphate restriction, dialysis, and the use of phosphate binders. The efficacy of phosphate binders may be inherently limited because the mechanism of action does not target any phosphate absorption pathway. Thus, therapeutic innovations are needed to address the limitations of phosphate binders. Novel therapies leveraging new mechanistic understandings of phosphate absorption and the primacy of the paracellular pathway may improve phosphate control. Phosphate absorption inhibitors that target the pathway are a novel therapeutic class. Tenapanor is an investigational first-in-class nonbinder phosphate absorption inhibitor that inhibits the sodium-hydrogen exchanger isoform 3 to reduce paracellular permeability specific to phosphate. Phosphate absorption inhibitors may represent a new mechanistic approach to phosphate management with the potential to improve clinical outcomes.