Assessment of ‘molecular organ age’ in pre-transplant kidney biopsies. Assessment of ‘molecular organ age’ 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. To better understand organ variability, we profiled the transcriptomes of n=271 deceased circulatory death kidneys at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal 1-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. Altogether, our work reveals the cellular molecular features of pathological organ ageing that can be identified at organ retrieval, with translational potential.