Kidney Week 2025 Annual Meeting-New Developments in Bones, Stones, and Mineral Metabolism

Video Transcription

Video Summary

This recorded ASN Kidney Week session covered new findings in bone–mineral metabolism, CKD complications, and related therapies.<br /><br />Dr. Mark Meyer described how FGF23 regulates renal vitamin D metabolism genomically. Using single-cell RNA-seq and ChIP-seq, his team identified the ETS-family transcription factor ETV1 as an FGF23-responsive factor that binds key enhancer regions controlling CYP24A1 (vitamin D catabolism) and correlates strongly with VDR binding. ETV1 physically interacts with ligand-bound VDR, enabling synergistic FGF23/1,25D effects. Surprisingly, PTH signaling rapidly removes ETV1 from the genome, likely via proteasomal mechanisms, offering a new model for coordinated FGF23–PTH control.<br /><br />Zhujia Zhang presented evidence that proximal-tubule–derived extracellular vesicles (EVs) carrying complement C3 enter the circulation and aggravate vascular calcification in CKD. Proteomics and imaging/tracing showed C3-rich tubular EVs reach vessels; tubular C3 knockdown reduced these EV signals and was linked to less calcification. Patient plasma EV C3 correlated with calcification severity.<br /><br />Dominic Kentrup reported that DMP1-knockout (ARHR1) mice develop age-dependent left ventricular hypertrophy from sustained FGF23 excess despite preserved kidney function. Females showed relative FGF23 resistance and milder LVH; bone-specific FGF23 deletion rescued cardiac changes.<br /><br />Tali Naveh-Many’s group showed leptin directly increases PTH secretion by inhibiting parathyroid calcium-sensing receptor signaling, linking energy and mineral metabolism.<br /><br />Eduardo Duque described reduced proximal-tubule HNF4A in CKD; tubule HNF4A deletion worsened fibrosis, caused phosphate wasting via SLC34A1/NPT2a suppression, and contributed to cortical bone loss.<br /><br />Clinical talks included MT1013 (a CaSR-activating, osteogenic peptide) lowering PTH and improving BMD in dialysis SHPT; denosumab improving trabecular microarchitecture in dialysis patients (best without mineralization defects); real-world romosozumab in advanced CKD showing spine BMD gains but frequent hypocalcemia and high cardiovascular event rates.<br /><br />Finally, Pietro Manuel-Ferreiro introduced a polygenic risk score predicting circulating 1,25D that associated with higher incident kidney stone risk, supporting a causal vitamin D–stone link.

Asset Subtitle

Moderator(s): Tanecia Mitchell, Julia Scialla

Presentation(s):

ETV1 Transcription Factor Mediates Fibroblast Growth Factor 23 (FGF-23) Genomic Control of Vitamin D Metabolism and PTH Suppression - Mark Meyer
Tubular Extracellular Vesicles Mediate Vascular Calcification in CKD via Complement C3 - Yu-xia Zhang
Fibroblast Growth Factor 23 (FGF-23) Induces Left Ventricular Hypertrophy in Mice with Autosomal Recessive Hypophosphatemia - Dominik Kentrup
Linking Energy and Mineral Metabolism: Leptin Inhibits the Calcium-Sensing Receptor to Stimulate Parathyroid Hormone Release - Alia Hassan, Tally Naveh-Many
Uncoupling CKD from MBD: Role of Proximal Tubule HNF4A in Mineral Metabolism and Kidney Function - Eduardo Duque
Efficacy and Safety of MT1013 in Patients with Secondary Hyperparathyroidism Undergoing Maintenance Dialysis - Chong Luo
Effect of Denosumab on Bone Mineral Density and Microarchitecture Assessed by High-Resolution Peripheral Quantitative CT (HRpQCT) in Bone Biopsies from Patients on Dialysis: A Longitudinal Study - Pablo Urena Torres
Romosozumab for Treatment of Osteoporosis in Advanced CKD: Series from Real-World Evidence - Arjunmohan Mohan
Polygenic Risk Score for Circulating 1,25-Hydroxyvitamin D and Application to Risk of Kidney Stones - Pietro Manuel Ferraro

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/6/2025

Session ID 519823

Keywords

ASN Kidney Week

bone-mineral metabolism

chronic kidney disease complications

FGF23 signaling

vitamin D metabolism

ETV1 transcription factor

VDR enhancer binding

PTH regulation

extracellular vesicles

complement C3

vascular calcification

secondary hyperparathyroidism therapies

dialysis bone disease