Renal functional reserve predicts GFR response to empagliflozin in RENALIS and RACELINES clinical trials

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Glomerular hyperfiltration is common in type 2 diabetes (T2D), potentially indicating reduced nephron number or altered intrarenal hemodynamics.
• Renal functional reserve (RFR) measures the kidney's capacity to increase glomerular filtration rate (GFR) with stimuli like meals, potentially revealing single-nephron hyperfiltration in T2D patients with normal GFR.

Purpose of the Study:

• To test if reduced postprandial RFR predicts the hemodynamic GFR response to empagliflozin in T2D.
• To determine if RFR predicts the GFR response to linagliptin or a sulfonylurea in T2D.

Main Methods:

• Pooled data from two 8-week randomized trials involving 71 T2D patients with preserved GFR.
• Patients received empagliflozin, linagliptin, or sulfonylurea plus metformin.
• Measured GFR (mGFR) and effective renal plasma flow (ERPF) were assessed under fasting and post-meal conditions; intrarenal hemodynamics and fractional sodium excretion were calculated.

Main Results:

• A protein-rich meal increased mGFR, ERPF, and decreased renal vascular resistance, driven by afferent arteriolar vasodilation.
• Postprandial mGFR changes correlated with postprandial renal vascular resistance changes.
• After 8 weeks, empagliflozin decreased mGFR, while linagliptin did not; sulfonylurea showed a trend towards decreased mGFR.
• Baseline postprandial mGFR changes significantly predicted 8-week mGFR changes with empagliflozin (r=0.88, P<0.001), but not with linagliptin or sulfonylurea.

Conclusions:

• Baseline postprandial RFR predicts GFR reduction with empagliflozin after 8 weeks in T2D patients.
• RFR does not predict GFR changes with linagliptin or sulfonylurea.
• RFR may serve as a tool to personalize SGLT2 inhibitor therapy, given its association with long-term kidney benefits.