TY - JOUR
T1 - GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading
AU - Haddock, Bryan
AU - Kristensen, Kasper B
AU - Tayyab, Mahvish
AU - Larsson, Henrik B W
AU - Lindberg, Ulrich
AU - Vestergaard, Mark
AU - Francis, Susan
AU - Jensen, Boye L
AU - Andersen, Ulrik B
AU - Asmar, Ali
PY - 2023/2/7
Y1 - 2023/2/7
N2 - Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.
AB - Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.
KW - Angiotensin II/pharmacology
KW - Cross-Over Studies
KW - Glucagon-Like Peptide 1/pharmacology
KW - Humans
KW - Kidney
KW - Kidney Medulla
KW - Male
KW - Perfusion
KW - Renal Circulation
KW - Sodium Chloride
KW - magnetic resonance imaging
KW - perfusion
KW - arterial spin labelling
KW - renal
KW - kidney
KW - RBF
KW - BOLD
KW - GLP‐1
UR - http://www.scopus.com/inward/record.url?scp=85147536345&partnerID=8YFLogxK
U2 - 10.1161/JAHA.122.027712
DO - 10.1161/JAHA.122.027712
M3 - Journal article
C2 - 36734354
VL - 12
SP - 1
EP - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 3
M1 - e027712
ER -