GLP-1's Effect on Renal Perfusion and Oxygenation Measured with Quantitative MRI: A Potential Renoprotective Pathway in the Human GLP-1-Renal Axis

Bryan Haddock, Kasper Birch Kristensen, Ulrich Lindberg, Susan T Francis, Boye Jensen, Ulrik Bjørn Andersen, Ali Asmar

Abstract

BACKGROUND
GLP-1 receptor agonism has shown significant beneficial cardiovascular effects that may be related to renoprotection. In the human kidney, a high GLP-1 extraction and its natriuretic effect are fully dependent on the GLP-1 receptor and associated with suppression of angiotensin II. Preclinical data showed that angiotensin II constricts vasa recta and lowers medullary blood flow. The current randomized and controlled study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion.

METHODS
Under fixed sodium intake (2 mmol NaCl/kg body weight/day) for 4 days before each study day, 10 lean healthy male participants were examined twice in random order during a 1-hour infusion of either GLP-1 (1.5 pmol/kg/min) or vehicle (0.9% NaCl) together with an intravenous infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal artery flow, oxygenation (R2*), and perfusion (arterial spin labeling) were acquired in the renal cortex and medulla, using Magnetic Resonance Imaging (MRI) during infusions.

RESULTS
During GLP-1 infusion, medullary perfusion increased 32 ± 7% (p<0.001) and cortical perfusion increased 13 ± 4% (p<0.001) compared to vehicle where medullary perfusion decreased -5 ± 2% (p=0.007) and cortical perfusion remained unchanged. R2* values increased 3 ± 2% (p=0.025) in the medulla and 4 ± 1% (p=0.008) in the cortex during vehicle infusion (indicative of decreased oxygenation) but remained unchanged during GLP-1 infusion. Renal arterial blood flow was not altered significantly by either intervention.

CONCLUSION
GLP-1 increases mainly medullary but also renal cortical perfusion and oxygenation during NaCl loading. In perspective, GLP-1 may promote Na excretion through this mechanism and exert long-term protective effects against hypoperfusion and ischemia.
OriginalsprogEngelsk
Publikationsdato4 nov. 2021
StatusUdgivet - 4 nov. 2021
BegivenhedAmerican Society of Nephrology, Kidney Week 2021 - Virtual, USA
Varighed: 4 nov. 20217 nov. 2021
https://www.asn-online.org/education/kidneyweek/2021/meeting-overview.aspx

Konference

KonferenceAmerican Society of Nephrology, Kidney Week 2021
LokationVirtual
Land/OmrådeUSA
Periode04/11/202107/11/2021
Internetadresse

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