Renal Warm Ischemia in Organ Donors After Circulatory Death

Abstract

Chronic kidney disease is the most common type of organ failure worldwide, with a prevalence of 13.4% for all stages. Organ transplantation is the only curative option for endstage kidney failure. However, shortage in organ donors remains a major obstacle in organ transplantation, with donation after circulatory death being the most viable path to increase the donor pool. The circumstances that surround this type of donation are different from donation after brain death, namely concerning warm ischemia times, which are longer and may preclude a successful transplantation. This article describes the pathophysiology of warm ischemia and summarizes recent developments in technological and methodological practices that mitigate the mechanisms of warm ischemia. Anoxia, mitochondrial dysfunction, calcium overload, oxidative and nitrosative stress, immune response and no-reflow are the main mechanisms by which ischemia leads to cell death and organ dysfunction. In-situ oxygenated recirculation, abdominal normothermic organ recirculation, abdominal hypothermic organ recirculation and ex-vivo machine perfusion ensure continued organ perfusion and prevent prolonged warm ischemia in organ donation. These, coupled with the optimization in the identification and assessment of potential donors after circulatory death may lead to a significant increase in the number and success rates of organ transplantation worldwide.

Reconstruction of a Lower Polar Artery for Kidney Transplantation Using Donor Ovarian Vein: Case Report with Literature Review

“…Since the duration of cold ischemia in a graft with an accessory artery is approximately 80 min and in a single artery allograft is 70 min, statistical significance has not been established [11,12]. If back-table preparation is not used, allograft transplantation with separate vascular anastomosis of the polar artery to the external iliac artery can prolong the warm ischemia time, resulting in an increased risk of acute tubular necrosis and decreased graft function [13]. Within 20 min of removing the kidney from the ice, the temperature can quickly increase above the metabolic threshold of 15 • C [14].…”

Donor-specific graft injury in solid organ transplantation: potential mechanisms and therapeutic strategies

“…In contrast to the cold ischemic injury of conventional DBD, the underlying pathophysiological mechanisms of warm ischemic kidney injury encountered during DCD procurement may be related to anoxia, calcium overload, mitochondrial dysfunction, oxidative & nitrosative stress, immune response, and ultimately lead to cell death and graft dysfunction ( 33 ). Moreover, hypoxia-inducible factors (HIFs) are crucial transcription factors for adaptive hypoxic responses, orchestrating the transcription of numerous genes involved in angiogenesis, erythropoiesis, glycolytic metabolism, and inflammation ( 34 ).…”