Multimodal Assessment of Kidney Quality During 24-h of Normothermic Machine Perfusion

Normothermic machine perfusion (NMP) has emerged as a promising tool for assessing kidney quality prior to transplantation; however, reliable biomarkers remain to be established.

In this study, thirteen porcine kidneys were perfused for 24 h using an autologous leukocyte-filtered whole blood-based perfusate applying urine recirculation. Functional, biochemical, and morphological parameters were assessed to comprehensively evaluate kidney quality.

Stable hemodynamics, sustained urine output, and oxygen consumption rates indicated preserved kidney viability. Within two hours of perfusion, microperfusion in renal cortex and ureter improved significantly, as confirmed by near-infrared, tissue hemoglobin, and oxygen saturation metrics. Morphological assessment revealed progressive injury localized in proximal tubular cells, marked by increased vacuolization, reduced microvilli density, and swollen mitochondria with protruding membranes. In contrast, the architecture of distal tubules and glomeruli remained intact. Biomarker analysis corroborated these findings, with KIM-1 and IGFBP-7 levels, two biomarkers predominantly expressed in proximal tubular cells, rising. Notably, overall OXPHOS capacity declined with perfusion duration, while ATP production efficiency remained stable. Histological grading, in concordance with real-time confocal assessment, showed no significant alteration over time.

This study provides a detailed phenotypical and bioenergetic profiling of kidney grafts over 24 h of NMP, demonstrating preserved kidney viability and function. The observed subcellular and molecular alterations, especially affecting the proximal tubules, were not reflected in frequently gathered metrics like hemodynamic flow, urine output, oxygen consumption, or lactate levels. Further studies are needed to confirm these findings and evaluate their clinical impact after transplantation.