Acute renal haemodynamic effects of GLP-1 receptor agonist exenatide in healthy overweight males

AIMS: To determine the acute effect of glucagon-like peptide-1 receptor agonist exenatide and the involvement of nitric oxide (NO) on renal haemodynamics and tubular function, in healthy overweight males.

MATERIALS AND METHODS: Renal haemodynamics and tubular electrolyte handling were measured in ten healthy overweight males (20-27 years; BMI 26-31 kg/m(2)) during intravenous administration of placebo (saline 0.9%), exenatide, and exenatide combined with the NO-synthase inhibitor L-N(G)-monomethyl arginine (L-NMMA). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance techniques, respectively, based on timed urine sampling. Glomerular hydrostatic pressure and vascular resistance of afferent and efferent renal arterioles were calculated using the Gomez formulae. Urinary electrolytes, osmolality and pH were also measured.

RESULTS: GFR and ERPF increased by mean 18±20 (+20%; P=0.021) and median 68 [26; 197] (+14%; P=0.015) mL/min/1.73m(2), respectively, during exenatide-infusion versus placebo. During L-NMMA-infusion, exenatide increased GFR by mean 8±12 mL/min/1.73m(2) (+9%; P=0.049). Exenatide increased estimated glomerular pressure by +6% (P=0.015) and reduced afferent renal vascular resistance by -33% (P=0.038), whereas these effects were blunted during L-NMMA. Exenatide increased absolute and fractional sodium excretion, urinary osmolality and urinary pH. Tubular effects of exenatide were not altered by concomitant L-NMMA.

CONCLUSIONS: Exenatide-infusion in healthy overweight males acutely increases GFR, ERPF and glomerular pressure, likely by reducing afferent renal vascular resistance, and at least partially in an NO-dependent manner. As baseline renal haemodynamics in type 2 diabetes patients differ from healthy subjects, clinical studies on renal effects of GLP-1 receptor agonists are warranted.