Assessment of real-time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast-enhanced ultrasonography vs para-aminohippuric acid clearance

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-N^G -monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans.

Methods: In 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.

Keywords: GLP-1 receptor agonist; contrast-enhanced ultrasonography; effective renal plasma flow; l-NMMA; para-aminohippuric acid; perfusion; renal hemodynamics.