DONOR diabetes-associated kidney transcriptomic signatures were identified in zero-hour kidney biopsies and subsequently assessed for changes after transplantation into non-diabetic recipients. The prospective observational study analysed biopsies collected between September 2021 and November 2022, providing insight into how molecular features associated with donor diabetes evolved following transplantation.
Researchers prospectively collected 288 zero-hour kidney biopsies from deceased donors. Biopsies from 43 donors with diabetes were compared with 86 propensity score-matched biopsies from donors without diabetes using microarray analysis. The aim was to identify transcripts associated with donor diabetes before examining whether these molecular signatures changed after transplantation.
The analysis identified 47 upregulated transcripts that discriminated kidneys from donors with diabetes from those from donors without diabetes. Aldo-ketoreductase transcripts, including AKR1C2, AKR1B10 and AKR1B15, were prominent among the upregulated transcripts.
Several fibrosis-associated transcripts were also prevalent, including VNN1, VCAN, CXCL6, IGHM, IGHA1 and JCHAIN. In contrast, 11 transcripts were downregulated, with the kallikrein-kinin system transcripts KLK1, KNG1 and SERPINF2 among those identified.
The researchers then assessed paired zero-hour and 3-month protocol biopsies from recipients without diabetes who received kidneys from donors with diabetes. This group comprised 13 donor-recipient pairs. Control groups included 26 pairs involving donors and recipients without diabetes and 11 pairs involving donors without diabetes and recipients with diabetes.
At 3 months, expression of the aldo-ketoreductase transcripts AKR1C2 and AKR1B10, together with NQO1, had decreased in kidneys from donors with diabetes transplanted into recipients without diabetes. Expression of SERPINF2 increased during the same period.
These changes were not observed in the control biopsy groups, supporting an association between transplantation into non-diabetic recipients and the observed evolution of selected donor diabetes-associated transcripts.
Overall, four transcripts associated with donor diabetes showed attenuation after transplantation in non-diabetic recipients. The findings highlight changes in kidney transcriptomic signatures over the early post-transplant period and provide molecular data on how donor diabetes-associated expression patterns may evolve after transplantation.
Reference
Girman P et al. Evolution of kidney transcriptomic signatures associated with donors’ diabetes in non-diabetic transplant recipients: prospective observational study. Sci Rep. 2026;DOI:10.1038/s41598-026-66323-5.
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