Randomized, Placebo-Controlled Trial on the Renal and Systemic Hemodynamic Effects of Empagliflozin

Area of Science:

• Nephrology
• Endocrinology
• Cardiovascular Medicine

Background:

• Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are established renoprotective agents in type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD).
• The mechanisms underlying SGLT2i's renal benefits may involve alterations in renal hemodynamics, including renal blood flow (RBF) and glomerular filtration rate (GFR).

Purpose of the Study:

• To investigate the specific renal and systemic hemodynamic effects of SGLT2 inhibitors in patients with DM2 and CKD.
• To compare these effects across different stages of kidney function and in non-diabetic CKD patients.

Main Methods:

• A double-blind, placebo-controlled, cross-over study design was employed.
• Patients with DM2 (eGFR >60 or 20-60 ml/min/1.73 m²) and non-diabetic CKD (eGFR 20-60 ml/min/1.73 m²) received empagliflozin 10 mg or placebo for 4 weeks, followed by a 2-week washout and cross-over.
• Renal blood flow (RBF) was assessed using ⁸²Rubidium-PET/CT, GFR using ⁹⁹mTechnetium-DTPA clearance, and 24-hour blood pressure (BP) and total vascular resistance (TVR) using Mobil-O-graph.

Main Results:

• Empagliflozin significantly reduced RBF by 6% in patients with DM2 and CKD (P < 0.001), with non-significant reductions in DM2 and CKD groups alone.
• Empagliflozin decreased GFR, BP, and TVR across all patient groups.
• Renal vascular resistance (RVR) remained unchanged in all groups.

Conclusions:

• Empagliflozin demonstrably reduces RBF in patients with DM2 and CKD, while lowering GFR, BP, and TVR in all studied groups.
• The observed hemodynamic changes, particularly the unchanged RVR, suggest that SGLT2 inhibitors exert protective effects on the glomerulus via combined preglomerular and postglomerular mechanisms.