Kidney Week 2025 Annual Meeting-Therapeutic Landscape for the Management of Diabetic Kidney Disease: What's Next After SGLT2 Inhibition?

Video Transcription

Video Summary

The session, moderated by Associate Professor Shradha Kotwal and Dr. Zhi, focused on the “next pillar” of therapy for diabetic kidney disease (DKD) beyond the established foundation of SGLT2 inhibitors, emphasizing additive, multi-mechanism treatment.<br /><br />Professor Peter Rossing reviewed aldosterone pathway targeting through mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASIs). Older steroidal MRAs (spironolactone/eplerenone) reduced albuminuria but were limited by hyperkalemia and poor adherence, with limited outcome benefits in CKD trials. Non-steroidal MRAs—especially finerenone—showed significant kidney and cardiovascular risk reduction in large trials (FIDELIO/FIGARO; pooled FIDELITY), with manageable hyperkalemia and minimal hormonal side effects. Subgroup data suggested benefits are maintained on top of SGLT2 inhibitors and GLP-1 receptor agonists. The randomized CONFIDENCE trial showed combination finerenone + SGLT2 inhibition lowered albuminuria more than either alone. Rossing also summarized emerging ASIs (baxdrostat, lorundrostat, vicadrostat), early albuminuria/BP effects, cortisol safety considerations, and ongoing outcome trials. New finerenone data in type 1 diabetes (FINE-1) demonstrated albuminuria lowering supporting “bridging” to outcomes evidence from type 2 diabetes.<br /><br />Dr. Masami Nangaku presented soluble guanylate cyclase (sGC) activators as therapies targeting endothelial dysfunction and impaired NO–cGMP signaling, particularly relevant in oxidative stress states like CKD/diabetes. Preclinical studies showed reduced fibrosis and proteinuria, sometimes outperforming sGC stimulators. Early clinical trials showed modest-to-moderate albuminuria reductions with tolerable adverse effects (hypotension, diarrhea, edema), with some mixed results across compounds.<br /><br />Dr. Maria Jose Soler discussed endothelin receptor antagonists (ERAs), explaining that blocking harmful ETA while preserving beneficial ETB signaling may reduce proteinuria with less fluid retention. The SONAR trial design mitigated edema risk via exclusions and enrichment. Newer studies suggest combining ERAs with SGLT2 inhibitors may enhance albuminuria lowering and reduce edema risk; larger outcome data are awaited.<br /><br />Dr. David Cherney outlined additional emerging targets: other proximal natriuretic approaches (e.g., carbonic anhydrase inhibition; sodium–amino acid transporter inhibitors), incretin-based therapies (FLOW trial with semaglutide showing cardiorenal benefit), dual/triple agonists under study, and anti-inflammatory strategies such as IL-6 blockade (ziltivekimab; ZEUS trial). Panel discussion highlighted growing challenges in defining “standard-of-care” control arms and the need for alternative biomarkers beyond albuminuria for non-hemodynamic drugs.

Asset Subtitle

Moderator(s): Sradha Kotwal, Di Xie

Presentation(s):

New Insights in Mineralocorticoid Receptor Antagonists and Aldosterone Synthase Inhibitors - Peter Rossing
Soluble Guanylyl Cyclase Inhibitors: Improving Endothelial Function and Kidney Outcomes - Masaomi Nangaku
Endothelin Receptor Antagonists: Can We Optimize Their Use by Adding to SGLT2 Inhibitors? - Maria Jose Soler
Novel Therapeutic Targets for DKD - David Cherney

Meta Tag

Date 11/6/2025

Pathway 1 Diabetic Kidney Disease

Session ID 507250

Keywords

diabetic kidney disease

DKD therapy

SGLT2 inhibitors

mineralocorticoid receptor antagonists

finerenone

FIDELIO-DKD

FIGARO-DKD

FIDELITY pooled analysis

aldosterone synthase inhibitors

baxdrostat

soluble guanylate cyclase activators

NO–cGMP signaling

endothelin receptor antagonists

albuminuria reduction

IL-6 blockade ziltivekimab