Kidney Week 2025 Annual Meeting-Have We Fully Exploited the Potential of SGLT2 Inhibitors for the Treatment of CKD?

Video Transcription

Video Summary

The session examined whether SGLT2 inhibitors’ kidney and cardiovascular benefits are fully exploited, especially in understudied populations.<br /><br />Volker Vallon reviewed mechanisms of kidney protection. By inhibiting proximal tubular glucose/sodium reabsorption, SGLT2 inhibitors shift transport downstream and activate tubuloglomerular feedback, lowering intraglomerular pressure and producing an initial, reversible eGFR “dip” that is functional rather than harmful and is associated with reduced AKI risk. He described combined afferent vasoconstriction and efferent dilation effects (via adenosine receptors), macula densa glucose sensing (SGLT1–NO), and reduced proximal tubular workload that may improve cortical oxygenation and limit glucotoxicity-driven inflammation/fibrosis. He highlighted coupled effects on other apical transporters (e.g., NHE3, URAT1) via protein interactions/scaffolding, explaining natriuresis, blood pressure reduction, and uricosuria. Potential off-target effects include microbiome changes that reduce uremic toxins (e.g., p-cresol), altered organic anion transporter expression, and possible protection from toxin-induced nephropathy even in SGLT2 knockout models.<br /><br />Ron Gansevoort addressed late-stage CKD, dialysis, and kidney transplantation. Post hoc analyses and meta-analyses suggest benefits may persist at low eGFR, with possible direct cardiac/vascular anti-inflammatory effects, but evidence is largely observational. He argued for caution in initiating therapy in these groups until prospective data are available, describing the ongoing international RENAL LIFECYCLE trial enrolling CKD G4–5, dialysis, and transplant recipients.<br /><br />Roman Ullrich-Müller reviewed ADPKD, where patients were excluded from major trials. Concerns include vasopressin increases and infection risk, while potential benefits include blood pressure/weight effects and ketosis-related pathways. Multiple small studies are ongoing, and two phase 3 trials (DAPAPKD and STOPP-PKD) aim to define efficacy and safety.<br /><br />Janet McGill focused on type 1 diabetes: SGLT2 inhibitors improve A1c and weight but consistently increase DKA risk (often euglycemic), limiting use. Continuous ketone monitoring and the SUGAR/SALT trial are proposed to address safety in T1D with CKD.

Asset Subtitle

Moderator(s): Moumita Barua, Brendon Neuen

Presentation(s):

Mechanism of Organ Protection with SGLT2 Inhibitors Beyond the SGLT2 Transporter - Volker Vallon
Effects of SGLT2 Inhibitors in Patients Receiving a Kidney Transplant or Dialysis - Ron Gansevoort
Are SGLT2 Inhibitors Safe and Effective in Patients with PKD? - Roman-Ulrich Mueller
Can We Use SGLT2 Inhibitors in Patients with Type 1 Diabetes and CKD? - Janet McGill

Meta Tag

Date 11/9/2025

Pathway 1 CKD Non-Dialysis

Pathway 2 Pharmacology

Session ID 507249

Keywords

SGLT2 inhibitors

kidney protection mechanisms

cardiovascular benefits

tubuloglomerular feedback

intraglomerular pressure reduction

eGFR dip

acute kidney injury risk reduction

proximal tubular glucose-sodium reabsorption

adenosine receptor hemodynamics

macula densa glucose sensing

NHE3 and URAT1 interactions

natriuresis and blood pressure lowering

late-stage chronic kidney disease (CKD G4–5)

dialysis and kidney transplantation

ADPKD and phase 3 trials (DAPAPKD, STOPP-PKD)