Renal functional reserve predicts GFR response to empagliflozin in RENALIS and RACELINES clinical trials
Abstract
Background: Glomerular hyperfiltration is common in type 2 diabetes (T2D) and may reflect reduced nephron number and/or perturbed intrarenal hemodynamics. Renal functional reserve (RFR), the capacity to increase glomerular filtration rate (GFR) with physiological stimuli (e.g. a meal), may help reveal single-nephron hyperfiltration in patients with preserved baseline whole-kidney GFR. We hypothesized that reduced postprandial RFR predicts the acute hemodynamic GFR response in T2D to the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, but not to the dipeptidyl-peptidase-4 inhibitor linagliptin or a sulfonylurea.
Methods: This analysis pooled data from two 8-week randomized, double-blind, parallel-group mechanistic trials, encompassing 71 T2D patients with preserved whole-kidney GFR [mean ± standard deviation age 65 ± 7 years, boby mass index 30.4 ± 3.9 kg/m2, glycated hemoglobin A1c 7.8 ± 1.0% (61.6 ± 11.0 mmol/mol), GFR 86.5 ± 17.6 mL/min/1.73 m2]. Patients received empagliflozin (10 mg; N = 20), linagliptin (5 mg; N = 27) or sulfonylurea (glimepiride 1 mg or gliclazide 30 mg; N = 24), in addition to metformin. Measured (m)GFR and effective renal plasma flow (ERPF) were determined by inulin/iohexol and para-aminohippurate clearance, respectively, based on timed urine sampling in fasting and post-protein-rich meal conditions. Intrarenal hemodynamics were calculated using Gomez equations; fractional sodium excretion (FENa) and systemic hemodynamics were…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 71 participants or records.
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