Kidney Week Educational Symposia-Targeting the Pathophysiology of Hyperphosphatemia in ESKD: From Physiology to Clinical Innovation

Video Transcription

Video Summary

This symposium reviewed phosphorus balance and why hyperphosphatemia is common and harmful in end-stage kidney disease (ESKD). In health, high dietary phosphate intake is largely offset by renal excretion, regulated mainly by parathyroid hormone (PTH) and FGF23, which increase urinary phosphate wasting. In chronic kidney disease, intestinal phosphate absorption remains relatively preserved (unlike calcium), partly because passive paracellular absorption is vitamin D–independent and driven by high luminal phosphate—especially from inorganic phosphate additives.<br /><br />In dialysis, phosphate removal is limited (typical thrice-weekly hemodialysis clears far less than average intake), and binders often remove only modest amounts and add pill burden; thus most dialysis patients remain hyperphosphatemic. Dietary counseling is complicated by undercounted phosphate additives and differences in bioavailability (additives > animal sources > plant phytate).<br /><br />Hyperphosphatemia is strongly associated with vascular calcification and mortality, but definitive randomized evidence that lowering phosphate improves hard outcomes is lacking; one major trial (HILO) stopped early. New approaches aim to reduce gut absorption directly: tenapanor inhibits NHE3 to reduce paracellular phosphate uptake, can synergize with binders, and commonly causes diarrhea. An ongoing pragmatic RCT (“PHOSPHATE”) is testing intensive vs liberal phosphate targets with cardiovascular outcomes, with results expected later this decade.

Asset Subtitle

Moderator(s): Jaime Uribarri

Presentation(s):

Introduction - Jaime Uribarri
Mechanisms of Hyperphosphatemia in ESKD: The Interplay of Physiology, Diet, and Pharmacotherapy - Julia Scialla
Hyperphosphatemia in ESKD: Is It Time for a Therapeutic Paradigm Shift? - Michal Melamed

Support is provided by an educational grant from Ardelyx, Inc.

Meta Tag

Date 10/25/2024

Pathway 1 Bones, Stones, and Mineral Metabolism

Pathway 2 Dialysis

Session ID 495603

Session Type ES - Educational Symposium

Keywords

phosphorus balance

hyperphosphatemia

end-stage kidney disease (ESKD)

chronic kidney disease (CKD)

FGF23

parathyroid hormone (PTH)

dialysis phosphate removal

phosphate binders

tenapanor