Effective management of hyperphosphatemia in chronic kidney disease (CKD) remains challenging despite dietary counseling, optimized dialysis, and the use of multiple oral phosphate binders.1 The physiologic burden of phosphate retention, driven by high dietary intake, enhanced intestinal absorption, and diminished renal excretion, continues to outpace the capacity of conventional interventions for many patients.2,3 As a result, persistent elevations in serum phosphate and treatment-related fatigue remain common in clinical practice.
Emerging therapies informed by improved understanding of intestinal phosphate handling offer new opportunities to complement existing approaches.1-3 Passive paracellular absorption accounts for a large proportion of daily phosphate uptake, while active transport mechanisms, including sodium-dependent cotransport and secondary active pathways, contribute variably depending on dietary intake, hormonal regulation, and intestinal segment.4 Interventions that modulate active transport aim to reduce phosphate absorption beyond the episodic window targeted by binder therapy and may provide more continuous control.1 Early studies evaluating inhibition of specific transport pathways demonstrate this mechanistic potential, although long-term efficacy and tolerability profiles will require continued evaluation across diverse patient populations.1
Translating these advances into clinical practice requires attention to real-world barriers. High pill burden, gastrointestinal symptoms, and the need for coordination with meals frequently impair adherence and limit the effectiveness of binder-dependent regimens.5,6 Simplified dosing schedules, mechanisms independent of food intake, or reductions in total medication load may therefore support improved persistence and patient experience when incorporated thoughtfully into individualized treatment plans and is an area of continued investigation.1,5
As therapeutic options broaden, clinicians face an evolving landscape that integrates physiologic insight with pragmatic care considerations. Ongoing research into both established and investigational therapies will be essential to define optimal sequencing, identify patient groups most likely to benefit from emerging mechanisms, and refine strategies that balance biochemical targets with quality-of-life outcomes.5,6
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