Kidney Week 2025 Annual Meeting-Glomerular Disease Outcomes: Measuring What Matters

Video Transcription

Video Summary

This oral abstract session featured multiple studies on glomerular diseases, emphasizing risk prediction, proteinuria as a treatment target, trial interpretation, and mechanistic insights.<br /><br />A multi-cohort IgA nephropathy analysis (QGEN, REGIONS, Columbia) compared clinical risk equations and tested whether adding polygenic risk scores (IgA PGS, CKD PGS, or both) improved prediction. Across diverse ancestries and ~6 years follow-up, the Tangri CKD equation consistently had the best discrimination and decision-curve clinical utility. Adding polygenic scores did not improve performance, suggesting routine clinical variables already capture much of the genetic risk signal.<br /><br />A large US retrospective IgA nephropathy cohort (TriNetX; n=745) evaluated time-averaged proteinuria (TAP) and outcomes (eGFR <15, >40% eGFR decline, dialysis, or death). Higher TAP—especially >1,000 mg/g—was associated with progressively worse outcomes. Importantly, improvement in TAP category over the first year reduced subsequent risk (~40% per category), supporting treat-to-target proteinuria strategies in US populations.<br /><br />CureGN data compared eGFR trajectories and composite outcomes across MCD, FSGS, membranous nephropathy, and IgA by age at biopsy. Overall, within-disease risks were broadly similar across age groups, reinforcing the need to include children in trials. Notable findings included faster eGFR decline in pediatric MCD and a small adolescent membranous subgroup with steep decline.<br /><br />An FSGS modeling study aligned a UK RaDaR registry cohort to the DUPLEX trial population to estimate long-term kidney-failure risk reductions from proteinuria responses. Achieving UPCR <0.3 or <0.7 at ~24 months strongly predicted lower kidney-failure risk, and DUPLEX’s ~26% proteinuria reduction was projected to translate into meaningful longer-term benefit.<br /><br />PROTECT trial biopsy review (IgA) showed sparsentan’s proteinuria-lowering effect was consistent across Oxford MEST-C lesions. Additional presentations covered falzartamab (anti-CD38) whole-blood RNA-seq showing immune/pathway shifts consistent with plasma cell targeting, atrasentan efficacy/safety in Asian IgA nephropathy patients, a halted lupus nephritis immunoproteasome inhibitor trial with safety concerns but biomarker/proteinuria signals, and a preeclampsia study implicating exosomal TMEM-106A/EGR1 in podocyte injury.

Asset Subtitle

Moderator(s): Yelena Drexler, Pietro Canetta

Presentation(s):

Impact of Polygenic Scores on Kidney Failure Risk Prediction Models in IgAN - Yan Ouyang
US Patients with IgAN and Low Proteinuria Have Significantly Better Kidney Survival than Participants in the UK RADAR Study - Nilang G. Patel
Glomerular Disease Outcomes Across the Lifespan: Report of the Cure Glomerulonephropathy (CureGN) Research Consortium - Margaret Helmuth
Estimating the Benefits of Proteinuria Reduction on Kidney Failure Risk in the DUPLEX Study Using an Aligned FSGS Cohort from the UK RaDaR Registry - Alex Mercer
Impact of Histology on Efficacy of Sparsentan Therapy in IgAN: Central Biopsy Review of Patients in the PROTECT Trial - Ian Roberts
Whole-Blood RNA Sequencing (RNAseq) Profiling Identifies Functionally Enriched Gene Expression Patterns in Felzartamab-Treated Patients with IgAN: Data from the Phase 2 IGNAZ Study - Millie Shah
Efficacy and Safety of Atrasentan in Patients (Pts) with IgAN from East (E) Asia: Phase 3 ALIGN Interim Data - Hong Zhang
Safety and Preliminary Efficacy of Zetomipzomib from the PALIZADE Phase 2b Clinical Trial in Patients with Lupus Nephritis - Samir Parikh
Exosome-Derived TMEM106A Participates in Podocyte Injury via EGR1 in Preeclampsia - Jinxiu Hu

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

Meta Tag

Date 11/7/2025

Pathway 1 Glomerular Diseases

Session ID 519874

Keywords

glomerular diseases

IgA nephropathy

risk prediction models

Tangri CKD equation

polygenic risk score

proteinuria treat-to-target

time-averaged proteinuria

CureGN cohort

eGFR trajectory

focal segmental glomerulosclerosis (FSGS)

DUPLEX trial modeling

sparsentan (PROTECT trial)

lupus nephritis trial safety