Kidney Week Educational Symposia-IgA Nephropathy: The Role of the Renal Endothelin System and Other Therapeutic Implications

Video Transcription

Video Summary

The session at ASN Kidney Week 2022 reviewed the rapidly changing treatment landscape for IgA nephropathy (IgAN), emphasizing proteinuria as both a key prognostic marker and a central clinical trial endpoint. Historically, IgAN care relied mainly on supportive therapy (maximizing renin–angiotensin system [RAS] blockade, blood pressure control, and lifestyle changes), while systemic steroids and immunosuppressants had uncertain benefit and significant toxicity. Improved understanding of IgAN mechanisms over the past 10–15 years has driven major growth in targeted therapies, better clinical trial designs, and the first FDA accelerated approval for IgAN (targeted-release budesonide).<br /><br />Dr. John Barratt focused on why proteinuria is pivotal: higher and sustained proteinuria predicts faster progression, and time-average proteinuria is strongly associated with kidney failure risk. Proteinuria is incorporated into the International IgAN Risk Prediction Tool and KDIGO guidance, helping stratify patients and trigger escalation beyond supportive care. However, proteinuria alone can misclassify risk, reinforcing the need for multi-variable risk tools and better biomarkers. Importantly, analyses from registries and randomized trials show early proteinuria reduction (7–12 months) predicts improved long-term outcomes, enabling shorter trials and accelerating drug development.<br /><br />Mechanistically, proteinuria reflects multiple injury pathways beyond mesangial immune complex deposition, including podocyte and tubular injury, complement amplification, and maladaptive hyperfiltration—making it an imperfect guide to choosing among therapies.<br /><br />Dr. Richard Lafayette reviewed treatment approaches: optimize supportive care, consider clinical trials for at-risk patients, use systemic steroids cautiously due to narrow risk–benefit, and prioritize safer options. Emerging therapies include SGLT2 inhibitors, targeted budesonide, complement inhibitors, B-cell–pathway agents, and especially endothelin receptor antagonists (including dual endothelin/ARB agents) with promising antiproteinuric effects. The key future challenge is matching the right drug(s) to the right patient at the right time, likely using combination therapy.

Asset Subtitle

Moderators: Tingting Li

Introduction - Tingting Li
Proteinuria in IgA Nephropathy: Mechanisms and Clinical Implications - Jonathan Barratt
Emerging Therapies in IgA Nephropathy: Targeting the Renal Endothelin System and Other Therapies - Richard Lafayette

Support is provided by an educational grant from Travere Therapeutics, Inc.

Meta Tag

Date 11/3/2022

Pathway 1 Glomerular Diseases

Pathway 2

Session ID 439549

Session Type ES - Educational Symposium

Keywords

IgA nephropathy

IgAN

proteinuria

ASN Kidney Week 2022

targeted-release budesonide

KDIGO guidelines

International IgAN Risk Prediction Tool

SGLT2 inhibitors

endothelin receptor antagonists

complement inhibitors