Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men

J Clin Endocrinol Metab. 2013 Apr;98(4):E664-71. doi: 10.1210/jc.2012-3855. Epub 2013 Mar 5.

Abstract

Introduction: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown.

Subjects and methods: Twelve healthy young males were examined in a randomized, controlled, double-blinded, single-day, crossover trial to evaluate the effects of 2 hours GLP-1 infusion on kidney functions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed with (51)Cr-EDTA and (123)I-hippuran, respectively, using a constant infusion renal clearance technique based on timed urine sampling.

Results: GLP-1 had no significant effect on either GFR [+1.9%, 95% confidence interval (-0.8; 4.6%)] or RPF [+2.4%, 95% confidence interval (-3.6; 8.8%)]. Fractional urine excretion of lithium increased 9% (P = .013) and renal sodium clearance increased 40% (P = .007). Angiotensin II decreased 19% (P = .003), whereas renin, aldosterone, and the urinary excretion of angiotensinogen showed no significant changes. glp-1 did not affect blood pressure but induced a small transient increase in heart rate.

Conclusion: The results indicate that although GLP-1 markedly reduces proximal tubule sodium reabsorption, the acute effects on GFR and RPF are very limited in healthy humans. The finding of GLP-1's ability to reduce angiotensin II concentration is novel and should be further elucidated.

Trial registration: ClinicalTrials.gov NCT01333163.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / pharmacology*
  • Health
  • Hemodynamics / drug effects*
  • Humans
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / physiology
  • Male
  • Placebos
  • Regional Blood Flow / drug effects
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology
  • Urinalysis
  • Young Adult

Substances

  • Placebos
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT01333163