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Acute renal haemodynamic effects of glucagon‐like peptide‐1 receptor agonist exenatide in healthy overweight men
Author(s) -
Muskiet M. H. A.,
Tonneijck L.,
Smits M. M.,
Kramer M. H. H.,
Diamant M.,
Joles J. A.,
van Raalte D. H.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12601
Subject(s) - exenatide , effective renal plasma flow , medicine , endocrinology , renal function , filtration fraction , urology , renal blood flow , type 2 diabetes , diabetes mellitus
Aims To determine the acute effect of glucagon‐like peptide‐1 ( GLP‐1 ) receptor agonist exenatide and the involvement of nitric oxide ( NO ) on renal haemodynamics and tubular function, in healthy overweight men. Methods Renal haemodynamics and tubular electrolyte handling were measured in 10 healthy overweight men (aged 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 G omez formulae. Urinary electrolytes, osmolality and pH were also measured. Results GFR increased by a mean of 18 ± 20 (+20%; p = 0.021) and ERPF increased by a median (interquartile range) of 68 (26; 197) ml/min/1.73 m 2 (+14%; p = 0.015) during exenatide infusion versus placebo. During L‐NMMA infusion, exenatide increased GFR by mean 8 ± 12 ml/min/1.73 m 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 infusion. Exenatide increased absolute and fractional sodium excretion, urinary osmolality and urinary pH . The tubular effects of exenatide were not altered by concomitant L‐NMMA infusion. Conclusions Exenatide infusion in healthy overweight men acutely increases GFR , ERPF and glomerular pressure, probably by reducing afferent renal vascular resistance, and at least partially in an NO ‐dependent manner. As baseline renal haemodynamics in patients with type 2 diabetes differ from those in healthy individuals, clinical studies on the renal effects of GLP‐1 receptor agonists are warranted.