Evolution of kidney transcriptomic signatures associated with donors’ diabetes in normoglycemic transplant recipients: prospective observational study

ABSTRACT: Deceased donors with diabetes have been considered suitable for kidney transplant recipients without diabetes, as long-term outcomes have generally been favorable, however little is known about mechanisms supporting this approach. The assessment of zero-hour transplant biopsies, including transcriptomic analysis, represents an innovative tool to study molecular signatures associated with diabetes and their evolution in subjects with different glycemic control. The aim of this study was to identify transcriptomic signatures associated with donor diabetes in zero-hour kidney biopsies, and to assess their evolution following transplantation into normoglycemic recipient. 288 deceased donor zero-hour kidney biopsies were prospectively collected in 2021-2022 and stored in RNAlater®. Transcriptomic profiles in biopsies of diabetic donors (n=43) and matched non-diabetic controls (n=86) were compared by microarray to identify diabetes-associated transcripts. Next, evolution of intrarenal transcriptome from zero-hour donor biopsy to 3-month protocol kidney graft biopsy was assessed by paired analysis in 50 diabetic (Dd+) and non-diabetic donors (Dd-) and their recipients either without (Rd-) or with diabetes (Rd+): Dd+⁄Rd-(n=13), Dd ⁄Rd+(n=11), Dd-⁄Rd-(n=26). Among the 47 upregulated transcripts discriminating diabetic donor kidneys from non-diabetic ones, aldo-ketoreductases (AKR1C2, AKR1B10 and AKR1B15) and transcripts associated with fibrosis (VNN1, VCAN, CXCL6 and IGHM, IGHA1, JCHAIN) were prevalent. Kallikrein-kinin system (KLK1, KNG1, and SERPINF2) were among 11 downregulated transcripts. Assessments of transcriptome evolution from zero-hour biopsy to 3-months protocol biopsy in Dd+/Rd- revealed decrease in expression of aldo-ketoreductases (AKR1C2, AKR1B10) and NQO1 (NAD(P)H quinone dehydrogenase 1) and increase of SERPINF2 (serpin family F member 2), however there were no changes in the expression of these transcripts in controls (Dd-/Rd-, Dd-/Rd+). We identified four intrarenal transcripts associated with donor diabetes whose deregulated expression were normalized after successful kidney transplantation in non-diabetic recipients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE295373 | GEO | 2026/09/30

REPOSITORIES: GEO