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

Abstract

Deceased donors with diabetes have been considered suitable for kidney transplant recipients without diabetes. The aim of this study was to identify transcriptomic signatures associated with donor diabetes in zero-hour kidney biopsies, and their changes after transplantation into non-diabetic recipients. Between September 2021 and November 2022, 288 deceased donor zero-hour kidney biopsies were prospectively collected. Biopsies from diabetic donors (Dd+, n = 43) were compared with propensity score–matched biopsies from non-diabetic donors (Dd−, n = 86) using microarray to identify diabetes-associated transcripts. Subsequently, paired analyses of corresponding zero-hour and 3-month protocol biopsies (diabetic donor/non-diabetic recipient pairs (Dd+/Rd−, n = 13)) were performed to study evolution of diabetes-associated transcripts after transplantation and as controls in biopsies from non-diabetic donors transplanted into non-diabetic (Dd−/Rd−, n = 26) or diabetic recipients (Dd−/Rd+, n = 11). Among the 47 upregulated transcripts discriminating diabetic donor kidneys from non-diabetic ones, aldo-ketoreductases ( AKR1C2 , AKR1B10 and AKR1B15 ) and fibrosis associated transcripts ( VNN1 , VCAN , CXCL6 and IGHM , IGHA1 , JCHAIN ) were prevalent. Kallikrein-kinin system ( KLK1 , KNG1 , and SERPINF2 ) were among 11 downregulated transcripts. Assessment of transcriptome evolution at 3-months protocol biopsy in Dd+/Rd- revealed decrease in expression of aldo-ketoreductases ( AKR1C2 , AKR1B10 ) and NQO1 and increase of SERPINF2 , without changes in the expression of these transcripts in controls. We identified four transcripts associated with donor diabetes whose expression attenuated after transplantation in non-diabetic recipients.