Soluble DNA Concentration in the Perfusate is a Predictor of Post-Transplant Renal Function in Hypothermic Perfused Kidney Allografts

Abstract

Introduction: Hypothermic machine perfusion (HMP) has greatly facilitated kidney allograft preservation. However, tissue damage still occurs during HMP, deleteriously affecting post-transplant graft function. Therefore, improved methods to assess organ quality and to predict post-transplant graft function and survival are needed. We propose that soluble DNA (sDNA) measured in HMP perfusate can used as a non-invasive biomarker for this purpose. Methods: Perfusate samples of kidney grafts placed on HMP were collected after 5 minutes and at the conclusion of HMP. sDNA of nuclear origin within the perfusate was quantified by real-time polymerase chain reaction and correlated with HMP parameters and post-transplant clinical outcomes. Results: Kidney grafts from 52 donors placed on HMP were studied. Perfusate sDNA concentration was significantly elevated in transplanted kidneys with delayed graft function. Grafts with higher concentrations of perfusate sDNA at 5min and at HMP conclusion also had reduced graft function in the initial post-transplant period, as measured by post-operative day 2, 3, and 4 creatinine reduction ratios (CRR). Standard pump parameters such as renal vascular resistance and renal vascular flow were poor indicators of early post-transplant graft function. Conclusion: sDNA concentration in HMP perfusate of kidney grafts can predict the quality of kidney graft preservation and indicate post-transplant renal function. This biomarker should be explored further to improve renal organ assessment and transplantation outcomes.