Kidney Week 2025 Annual Meeting-Incretin-Based Therapies in Nephrology

Video Transcription

Video Summary

The session, co-moderated by nephrologists Ricardo Correa-Rotter and Caitlin Mayne, reviewed the rapidly expanding role of GLP‑1–based therapies. Endocrinologist Jennifer Green outlined GLP‑1 physiology (enhanced insulin, suppressed glucagon, appetite reduction, delayed gastric emptying) and emphasized widespread GLP‑1 receptors across organs, helping explain benefits beyond diabetes and obesity—cardiovascular disease, heart failure, liver disease, kidney disease, and osteoarthritis. She highlighted next-generation agents: dual agonists (GLP‑1/GIP; e.g., tirzepatide), GLP‑1/glucagon combinations, and triple agonists (e.g., retatrutide), which can achieve ~22–24% weight loss. Emerging areas include neurodegenerative disease and substance use disorders (preliminary/mixed evidence) and intriguing observational signals for post-transplant organ protection. Key challenges remain: weight regain after stopping therapy, uncertain effects on skeletal muscle and body composition, and cost/access.<br /><br />A nephrology-focused talk detailed mechanisms for kidney protection: GLP‑1–mediated natriuresis (likely via proximal tubule NHE3), effects on renal hemodynamics through nitric oxide and reduced angiotensin II, potential endothelin-1 interactions, reductions in perirenal fat, anti-inflammatory actions, and blood pressure lowering partly independent of weight loss. Trial evidence in non-diabetic CKD showed reduced albuminuria (SMART) and improved kidney outcomes and eGFR slope in a large obesity/CVD trial (SELECT).<br /><br />Guido Heerspink reviewed outcome trials: semaglutide reduced kidney and cardiovascular events in diabetic CKD (FLOW) and benefits seemed largely weight-independent. Mechanistic data (REMODEL) suggested reduced renal fat, improved vascular resistance, and stabilized cortical fibrosis. Tirzepatide showed kidney benefits versus active comparator, and retatrutide raised questions about sustained eGFR increases; major mechanistic and outcomes trials are underway. Combination therapy with SGLT2 inhibitors appears additive.<br /><br />Endocrinologist Daniel van Raalte summarized adverse-effect management: gastrointestinal effects are common and drive real-world discontinuation; slow titration, dietary counseling, and short-term symptom medications can help. Rapid glucose lowering can transiently worsen diabetic retinopathy, warranting eye monitoring in high-risk patients. Gallbladder disease risk rises with weight loss; pancreatitis risk is not clearly increased. Clinicians must down-titrate insulin and antihypertensives to avoid hypoglycemia and hypotension.

Asset Subtitle

Moderator(s): Ricardo Correa-Rotter, Kaitlin Mayne

Presentation(s):

GLP-1 Receptor Agonist Landscape: From Single to Triple-G Therapies and Beyond - Jennifer Green
Incretin Biology and Nondiabetic Kidney Diseases - Ayodele Odutayo
Update on the GLP-1 Receptor Agonist End Point Trials: Which Questions Remain Unanswered? - Hiddo Heerspink
GLP-1 Receptor Agonist-Based Therapies in Nephrology Practice and Adverse Effect Management - Daniël van Raalte

Meta Tag

Date 11/8/2025

Pathway 1 Diabetic Kidney Disease

Pathway 2 Kidney Biology and Physiology

Session ID 507086

Keywords

GLP-1 receptor agonists

GLP-1 physiology

semaglutide

tirzepatide

retatrutide

dual incretin agonists (GLP-1/GIP)

triple agonists

chronic kidney disease (CKD)

kidney protection mechanisms

natriuresis and NHE3 proximal tubule

renal hemodynamics (nitric oxide, angiotensin II)

albuminuria reduction

FLOW trial

SELECT trial

adverse effect management (GI, retinopathy, gallbladder)