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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Zhang, Roy 
Trotter, Patrick B 
McCaffrey, James 
Fitzroy, Rory 
Trivioli, Giorgio 

Abstract

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.

Description

Keywords

aging, deceased circulatory death donor, retrieval biopsy, transcriptomics, transplantation, Humans, Kidney Transplantation, Kidney, Biopsy, Middle Aged, Male, Adult, Female, Transcriptome, Gene Expression Profiling, Aged, Age Factors, Tissue Donors, Aging, Pathology, Molecular, Immunity, Innate, Adaptive Immunity, Young Adult, Single-Cell Analysis, Graft Survival

Journal Title

Kidney Int

Conference Name

Journal ISSN

0085-2538
1523-1755

Volume Title

Publisher

Elsevier BV