Assessment of biological organ age using molecular pathology in pre-transplant kidney biopsies.
Kidney Int
; 106(2): 302-316, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38692408
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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Perfilação da Expressão Gênica
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Transcriptoma
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Rim
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2024
Tipo de documento:
Article