Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy

Abstract

Understanding and measuring parameters responsible for the pathogenesis of sepsis-induced AKI (SI-AKI) is critical in developing therapies. Blood flow to the kidney is heterogeneous, partly due to the existence of dynamic networks of capillaries in various regions, responding differentially to oxygen demand in cortex versus medulla. High energy demand regions, especially the outer medulla, are susceptible to hypoxia and subject to damage during SI-AKI. Proximal tubule epithelial cells in the cortex and the outer medulla can also undergo metabolic reprogramming during SI-AKI to maintain basal physiological status and to avoid potential damage. Current data on the assessment of renal hemodynamics and oxygen metabolism during sepsis is limited. Preclinical and clinical studies show changes in renal hemodynamics associated with SI-AKI, and in clinical settings, interventions to manage renal hemodynamics seem to help improve disease outcomes in some cases. Lack of proper tools to assess temporospatial changes in peritubular blood flow and tissue oxygen metabolism is a barrier to our ability to understand microcirculatory dynamics and oxygen consumption and their role in the pathogenesis of SI-AKI. Current tools to assess renal oxygenation are limited in their usability as these cannot perform continuous simultaneous measurement of renal hemodynamics and oxygen metabolism. Multi-parametric photo-acoustic microscopy (PAM) is a new tool that can measure real-time changes in microhemodynamics and oxygen metabolism. Use of multi-parametric PAM in combination with advanced intravital imaging techniques has the potential to understand the contribution of microhemodynamic and tissue oxygenation alterations to SI-AKI.

Keywords: Acute kidney injury; Hemodynamics; Oxygen metabolism; Photoacoustic microscopy; Sepsis.

Fig. 1.

Photoacoutic microscopy. Photo-acoustic microscopy is a hybrid of optics and ultrasound. In photoacoustic microscopy, usually, a focused laser pulse is directed into biological tissue (kidney). The tissue absorbs light and induces transient heating. The thermoelastic expansion of the tissue converts the heat into acoustic emission. A transducer outside of the tissue can detect the acoustic wave and form an image. The conversion from optical absorption to acoustic emission has a few unique advantages. First, photoacoustic imaging is solely sensitive to optical absorption creating a very specific imaging contrast. Second, relying on focused acoustic detection photoacoustic microscopy can operate beyond the penetration of pure optical microscopy.