Assessment of real-time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast-enhanced ultrasonography vs para-aminohippuric acid clearance
Muskiet, Marcel H A; Emanuel, Anna L; Smits, Mark M; Tonneijck, Lennart; Meijer, Rick I; Joles, Jaap A; Serné, Erik H; van Raalte, Daniël H
(2019) Microcirculation, volume 26, issue 7
(Article)
Abstract
OBJECTIVE: To determine the ability of renal contrast-enhanced ultrasonography (CEUS) to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide (GLP)-1 receptor agonist exenatide and nitric oxide [NO]-synthase inhibitor L-NG -monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans. METHODS: In
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this prespecified exploratory analysis of a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27 years; BMI 26-31 kg/m2 ) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences. Renal cortical microvascular blood flow was compared with simultaneously measured effective renal plasma flow in humans, derived from para-aminohippuric acid-clearance methodology. RESULTS: On Day-A, effective renal plasma flow increased by 68 [26-197] mL/min/1.73 m2 during exenatide vs placebo infusion (+17%; P = .015). In parallel, exenatide increased renal cortical microvascular blood flow, from 2.42 × 10-4 [6.54 × 10-5 -4.66 × 10-4 ] AU to 4.65 × 10-4 [2.96 × 10-4 -7.74 × 10-4 ] AU (+92%; P = .027). On Day-B, effective renal plasma flow and renal cortical microvascular blood flow were reduced by l-NMMA, with no significant effect of concomitant exenatide on renal hemodynamic-indices assessed by either technique. Effective renal plasma flow correlated with renal cortical microvascular blood flow on Day-A (r = .533; P = .027); no correlation was found on Day-B. CONCLUSIONS: Contrast-enhanced ultrasonography can detect acute drug-induced changes human renal hemodynamics. CEUS-assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal-to-high range. Renal CEUS cannot replace effective renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion.
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Keywords: Adult, Blood Flow Velocity/drug effects, Contrast Media/administration & dosage, Humans, Kidney, Male, Microcirculation/drug effects, Overweight/diagnostic imaging, Pilot Projects, Ultrasonography, omega-N-Methylarginine/administration & dosage, perfusion, effective renal plasma flow, para-aminohippuric acid, contrast-enhanced ultrasonography, renal hemodynamics, GLP-1 receptor agonist, l-NMMA, Cardiology and Cardiovascular Medicine, Physiology (medical), Molecular Biology, Physiology, Research Support, Non-U.S. Gov't, Randomized Controlled Trial, Journal Article
ISSN: 1073-9688
Publisher: Wiley-Blackwell
Note: Funding Information: Funding information The research leading to the results of this study has received funding from the European Community's Seventh Framework Program (FP7/2007-2013) under grant agreement nº 282521 – the SAFEGUARD project; and the Dutch Kidney Foundation, under grant agreement IP12.87. Funders had no role in the study design, in collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors extend their gratitude to all the study participants who took part in these studies for their time and commitment to the demanding protocols. We thank J. Boerop and S. Gassman (Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands) for their excellent practical support during the test visits. The technical laboratory assistance of A. Dijk and N. Willekes-Koolschijn (Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands) was much appreciated. Publisher Copyright: © 2019 John Wiley & Sons Ltd
(Peer reviewed)