Association of Contrast-Enhanced Ultrasound-Derived Kidney Cortical Microvascular Perfusion with Kidney Function

Background Individuals with chronic kidney disease (CKD) have decreased kidney cortical microvascular perfusion, which may lead to worsening kidney function over time, but methods to quantify kidney cortical microvascular perfusion are not feasible to incorporate into clinical practice. Contrast-enhanced ultrasound (CEUS) may quantify kidney cortical microvascular perfusion, which requires further investigation in individuals across the spectrum of kidney function. Methods We performed CEUS on a native kidney of 83 individuals across the spectrum of kidney function and calculated quantitative CEUS-derived kidney cortical microvascular perfusion biomarkers. Participants had a continuous infusion of the microbubble contrast agent (Definity) with a flash-replenishment sequence during their CEUS scan. Lower values of the microbubble velocity (beta) and perfusion index (beta XA) may represent lower kidney cortical microvascular perfusion. Multivariable linear regression models tested the associations of the microbubble velocity (beta) and perfusion index (beta XA) with estimated glomerular filtration rate (eGFR). Results Thirty-eight individuals with CKD (mean age +/- SD 65.2 +/- 12.6 years, median [IQR] eGFR 31.5 [18.9-41.5] ml/min per 1.73 m(2)), 37 individuals with end stage kidney disease (ESKD; age 54.8 +/- 12.3 years), and eight healthy volunteers (age 44.1 +/- 15.0 years, eGFR 117 [106-120] ml/min per 1.73 m(2)) underwent CEUS without side effects. Individuals with ESKD had the lowest microbubble velocity (beta) and perfusion index (beta XA) compared with individuals with CKD and healthy volunteers. The microbubble velocity (beta) and perfusion index (beta XA) had moderate positive correlations with eGFR (beta: r(s)=0.44, P < 0.001; beta XA: r(s)=0.50, P < 0.001). After multivariable adjustment, microbubble velocity (beta) and perfusion index (beta XA) remained significantly associated with eGFR (change in natural log transformed eGFR per 1 unit increase in natural log transformed biomarker: beta, 0.38 [95%, CI 0.17 to 0.59]; beta XA, 0.79 [95% CI, 0.45 to 1.13]). Conclusions CEUS-derived kidney cortical microvascular perfusion biomarkers are associated with eGFR. Future studies are needed to determine if CEUS-derived kidney cortical microvascular perfusion biomarkers have prognostic value.