Functional recovery of donated kidneys after uncontrolled circulatory death - From lab to patient

Abstract

Kidney transplantation is the best treatment for end-stage renal disease, yet fewer than one in ten who need one receive it. Kidneys from uncontrolled donation after circulatory death (uDCD) are the largest untapped organ source but are almost all discarded, because prolonged warm ischemia causes a microvascular obstruction and a persistent no-reflow state. This thesis asked whether that obstruction, rather than warm-ischemia time itself, is the reversible barrier to recovery, testing whether thrombolysis followed by ex-vivo machine perfusion restores function in a porcine model (Papers I–III) and human kidneys (Paper IV). Treatment cleared the obstruction; 62% of recipients survived on the reconditioned graft alone, whereas all untreated recipients died within five days (Paper I), and treated kidneys sustained their recipients for three months as the sole graft (Paper II). Proteomics showed that the retrieval injury signature resolved with no residual iron-overload, indicating that treatment averted ferroptosis (Paper III); in human kidneys after nearly seven hours of warm ischemia, four of eight met the predefined perfusion criteria (Paper IV). Prolonged warm ischemia should therefore not, by itself, indicate irreversible injury; fully developed, the method could substantially reduce organ shortages by returning the large uDCD pool to clinical use.