Kidney Week

Abstract: TH-OR078

Renal Functional Reserve Predicts GFR Response to Empagliflozin but Not Linagliptin or Sulfonylureas in Patients with Type 2 Diabetes

Session Information

• Precision Medicine in Diabetic Kidney Disease: Biomarkers, Combination Therapies, and Treatment Response Prediction
  November 06, 2025 | Location: Room 372A, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Muskiet, Marcel, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands

Marcel Muskiet, MD, PhD

• van Baar, Michael, Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands

Michael van Baar, MD

• Touw, Daniel J., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Daniel J. Touw, PharmD, PhD

• Krebber, Merle M., Universitair Medisch Centrum Utrecht, Utrecht, UT, Netherlands

Merle M. Krebber, PhD

• Cherney, David, University Health Network, Toronto, Ontario, Canada

David Cherney, MD, PhD

• Bjornstad, Petter, University of Washington School of Medicine, Seattle, Washington, United States

Petter Bjornstad, MD

• van Raalte, Daniël H., Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands

Daniël H. van Raalte, MD, PhD

Background

Glomerular hyperfiltration is common in type 2 diabetes (T2D) and may be due to reduced nephron number and/or altered intrarenal hemodynamics. Renal functional reserve (RFR), the kidney’s ability to increase GFR upon stimulation (e.g., a meal), can help identify single-nephron hyperfiltration in patients with preserved baseline (BL) whole-kidney GFR. We evaluated whether postprandial RFR is associated with an acute hemodynamic GFR response to SGLT2i empagliflozin (EMPA), DPP-4i linagliptin (LINA), or a sulfonylurea (SU) in T2D.

Methods

This analysis pools data from two 8-week randomized, double-blind, parallel-group trials, including 71 T2D patients with preserved whole-kidney GFR (mean±SD age 65±7 yrs, 83% male, BMI 30.4±3.9 kg/m², HbA1c 7.8±1.0%, measured (m)GFR 86.5±17.6 mL/min/1.73m²). Patients received EMPA (10mg; N=20), LINA (5mg; N=27) or SU (glimepiride 1mg or gliclazide 30mg; N=24), added to stable metformin. mGFR and effective renal plasma flow (ERPF) were determined by inulin/iohexol and PAH-clearance, respectively, based on timed urine sampling in fasting and post-protein-rich meal conditions. Intrarenal hemodynamics were calculated using Gomez-equations, and fractional sodium excretion (FE_Na) and systemic hemodynamics were also evaluated.

Results

The meal increased mGFR (+7.3±1.7 mL/min/1.73m²; p<0.001) and ERPF (+44.3±14.9 mL/min/1.73m²; p=0.005), with a decrease in renal vascular resistance (RVR; −0.02±0.01 mmHg/L/min; p<0.001), likely driven by reduced afferent arteriolar resistance (−1068±241 dyne/sec/cm^-5; p<0.001) and lower FE_Na (−0.21±0.05; p<0.001). Postprandial mGFR-changes correlated with BL HbA1c (r:0.29; p=0.032) but not with BL mGFR, and postprandial RVR change (r −0.57; p<0.001). After 8 weeks, mGFR tended to decrease with SU (p=0.054) and decreased with EMPA (−9.1±3.2 mL/min/1.73m²; p=0.016), with no effect with LINA. BL postprandial mGFR changes correlated with 8-week treatment-induced mGFR changes across all patients; strongly in the EMPA group (r:0.88; p<0.001), but not with LINA or SU.

Conclusion

Postprandial RFR links to the acute GFR dip with EMPA, but not GFR changes in response to LINA or SU. As initial GFR-dipping is associated with long-term kidney benefit, RFR may be a potential biomarker to personalize SGLT2i-therapy.

Funding

• Commercial Support – Boehringer Ingelheim

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20250g4wmdg7