Dynamic Contrast-Enhanced Ultrasound Identifies Microcirculatory Alterations in Sepsis-Induced Acute Kidney Injury

Objectives: We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Design: Prospective controlled animal experiment study. Setting: Hospital-affiliated animal research institution. Subjects: Fifteen female pigs. Interventions: The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Measurements and Main Results: Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. Conclusions: In our lipopolysaccharide model, with resuscitation targeted at blood pressure, the contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation. Drs. Lima and van Rooij contributed equally as first authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/29S62lw). Supported, in part, by an Innovation Grant of the Dutch Kidney Foundation (14 OI 11), NanoNextNL, a micro- and nanotechnology consortium of the Government of the Netherlands and by the European Erasmus + Traineeship program. Dr. Lima’s, de Jong’s, and Ince’s institution received funding from the Dutch Kidney Foundation. Dr. van Rooij’s institution received funding from NanoNextNL, and he received support for article research from NanoNextNL and the Dutch Kidney Foundation. Dr. Ince received funding from the Dutch Kidney Foundation (Innovation Grant), and he received support for article research from the Dutch Kidney Foundation. Dr. Mik disclosed he is a founder and shareholder of Photonics Healthcare B.V. (Utrecht, The Netherlands); this company build a device for measuring mitochondrial oxygen tension, but this is not related to the subject of the article. Dr. Kooiman’s institution received funding from NanoNextNL; a Veni grant from Dutch Scientific Organization, division Toegepaste en Technische Wetenschappen; a fellowship grant from Erasmus MC Foundation; and a Grant from Phospholipid Research Center. Dr. Kooiman received funding from Erasmus MC (employer). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: a.pintolima@erasmusmc.nl Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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