Assessment of biological organ age using molecular pathology in pre-transplant kidney biopsies.

Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential.

Use of Organs From Hepatitis C Virus-Positive Donors for Uninfected Recipients: A Potential Cost-Effective Approach to Save Lives?

BACKGROUND: Organs from hepatitis C virus (HCV) seropositive (HCVpos) individuals are seldom used for transplantation because of the risk of disease transmission. Because transmitted HCV is now amenable to effective treatment, we estimated the potential impact of using HCVpos deceased donor organs for transplantation. METHODS: The Potential Donor Audit of patients (<80 years) dying in UK critical care units and the UK Transplant Registry was searched to identify HCVpos potential and proceeding deceased donors. Donor organ quality was assessed using validated donor organ quality indices. Cost analysis was performed by comparing the cumulative cost of direct-acting antivirals with hemodialysis and renal transplantation. RESULTS: Between 2009 and 2016, 120 patients identified from the Potential Donor Audit were not considered as potential donors because of the presence of HCV. Between 2000 and 2015, 244 HCVpos potential deceased donors were identified from the UK Transplant Registry, and 76 (31%) proceeded to donation, resulting in 63 liver, 27 kidney, and 2 heart transplants. Recipient and graft survival was not adversely impacted by donor HCVpos status. Most (69%) offered organs were declined because of positive virology although their quality was similar to that of other transplanted organs. The additional costs of treating recipients exposed to HCV by receiving a HCVpos kidney was cost-neutral with dialysis 5 years from transplantation. CONCLUSIONS: HCVpos donors represent a potential source of organs for HCV seronegative recipients as many good quality HCVpos donor organs are not currently used for transplantation. This change in practice may increase access to transplantation without having an adverse effect on transplant outcome.