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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by an ASTS-CareDx Career Development Grant and by NIH/NIDDK K08DK113244 (AZ). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of University of Florida gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors