Kidney Week 2025 Annual Meeting-Iron and Mineral Metabolism: A Complex Relationship, Including the Jack W. Coburn, MD, Endowed Lectureship

Video Transcription

Video Summary

The session, “Iron and Mineral Metabolism: a Complex Relationship,” brings together basic physiology and clinical consequences of disordered iron handling—especially in CKD—and its emerging links to phosphate metabolism via FGF23.<br /><br />Jodi Babbitt reviews iron homeostasis centered on hepcidin, a liver peptide that inhibits ferroportin to block intestinal iron absorption and iron release from macrophage stores. In CKD, hepcidin is elevated due to inflammation and reduced renal clearance, contributing to iron-restricted erythropoiesis and anemia. Her lab’s work identifies BMP–SMAD signaling as the key transcriptional driver of hepcidin. Liver endothelial cells produce BMP2 and BMP6, which appear to act cooperatively—likely as a potent heterodimer—to induce hepcidin; BMP5 provides backup when BMP2/6 are limited. Erythropoietic drive suppresses hepcidin through erythroferrone from bone marrow, which binds and sequesters BMP ligands, reducing BMP signaling.<br /><br />Guillaume Corbeau focuses on bidirectional links between iron status and FGF23. Inflammation causes functional iron deficiency and increases FGF23 transcription with predominant cleavage (high total/c-terminal vs intact FGF23), while CKD can shift toward higher intact FGF23. True iron deficiency (low stores) also raises FGF23, impairs bone microarchitecture, and induces oxidative stress/inflammatory programs in bone. Erythroblasts are a major source of FGF23 in iron deficiency and CKD; locally, intact FGF23 can inhibit erythroid differentiation via FGFR1, suggesting paracrine effects.<br /><br />Jay Wish summarizes clinical data showing iron deficiency has important non-anemic consequences (mitochondrial function, HIF signaling, fatigue). Heart failure trials largely support IV iron improving symptoms and reducing hospitalizations, including in CKD subgroups. In hemodialysis (PIVOTAL), proactive IV iron (higher ferritin targets) reduced cardiovascular events and ESA dose without clear safety penalties, though mechanisms remain debated.<br /><br />Myles Wolfe delivers the Coburn lecture on IV iron–induced hypophosphatemia, especially with ferric carboxymaltose. In iron deficiency, FGF23 production rises but is usually cleaved; ferric carboxymaltose uniquely increases intact FGF23, driving renal phosphate wasting, low calcitriol, secondary hyperparathyroidism, prolonged hypophosphatemia, osteomalacia, and fractures. Prevention (choosing alternative iron formulations and monitoring phosphate) is emphasized because treatment with phosphate/vitamin D is often ineffective.

Asset Subtitle

Moderator(s): Christian Faul, Farzana Perwad

Presentation(s):

Bone Morphogenic Proteins in Iron Homeostasis - Jodie Babitt
Complex Relationship Between Iron and FGF23 - Guillaume Courbon
Iron Replacement Beyond Anemia Therapy - Jay Wish
Iron-Induced Hypophosphatemia: A Still Unrecognized Complication of Iron Replacement: The Jack W. Coburn, MD, Endowed Lectureship - Myles Wolf

ASN gratefully acknowledges Amgen for support of the Coburn Endowed Lectureship.

Meta Tag

Date 11/8/2025

Pathway 1 CKD Non-Dialysis

Session ID 507292

Keywords

iron homeostasis

hepcidin

ferroportin

chronic kidney disease (CKD) anemia

iron-restricted erythropoiesis

BMP–SMAD signaling

BMP2/BMP6 heterodimer

erythroferrone

FGF23 regulation

functional iron deficiency

intact vs c-terminal FGF23 cleavage

phosphate metabolism

intravenous iron therapy

ferric carboxymaltose hypophosphatemia

renal phosphate wasting and osteomalacia