Kidney Week

Abstract: FR-OR092

Impact of Glomerular Filtration Rate and Albuminuria on the Effects of SGLT2 Inhibitors on Kidney Outcomes

Session Information

• Late-Breaking Research Orals - 2
  November 07, 2025 | Location: Grand Ballroom C, Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Neuen, Brendon Lange, The George Institute for Global Health, Sydney, New South Wales, Australia

Brendon Lange Neuen, MBBS, MS, PhD, FASN

• Fletcher, Robert A., The George Institute for Global Health, Sydney, New South Wales, Australia

Robert A. Fletcher, MSc

• Perkovic, Vlado, The George Institute for Global Health, Sydney, New South Wales, Australia

Vlado Perkovic, MBBS, PhD, FASN

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Hiddo Jan L. Heerspink, PhD

Group or Team Name

• SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C).

Background

SGLT2i reduce CKD progression in individuals with diabetes, CKD or heart failure. However, their effects in those with stage 4 CKD or little to no albuminuria are less clear.

Methods

We conducted inverse variance weighted meta-analysis of trials within the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, assessing heterogeneity across eGFR (<20, 20-<30, 30-<45, 45-<60, and ≥60 mL/min/1.73m²) and UACR (<30, 30-300, >300-1000, >1000 mg/g) categories. The primary outcome was kidney failure, ≥50% reduction in eGFR, or kidney-related death. Other outcomes included chronic eGFR slope and kidney failure.

Results

Across 10 trials, 2,314/70,361 (3.3%) experienced CKD progression, and 988 (1.1%) reached kidney failure. SGLT2i reduced CKD progression (HR 0.62, 95% CI 0.57-0.68) irrespective of eGFR or UACR (P-heterogeneity=0.49 and 0.31; Fig 1). SGLT2i also reduced kidney failure alone (HR 0.66, 95% CI 0.58-0.75). While the magnitude of protection varied, clear benefits on chronic eGFR slope were observed across all subgroups apart from eGFR <20 mL/min/1.73m², where there were too few participants to reliably evaluate treatment effects (Fig 2).

Conclusion

SGLT2i reduce CKD progression across the spectrum of eGFR and albuminuria, including those with stage 4 CKD and little to no albuminuria.

Figure 1. Effects of SGLT2i on CKD progression according to baseline eGFR and UACR

Figure 2. Effect of SGLT2i on chronic eGFR slope according to baseline eGFR and UACR

Funding

• Government Support - Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025bs338s8x