Abstract
Donor kidney tissue-based transcriptomics may represent a new dimension for the prediction of kidney transplant outcomes. In this prospective, single-center study, 276 kidneys from 174 deceased brain-death donors were assessed by microarrays to identify phenotypes of procurement biopsies. Molecular classifiers (extreme gradient boosting, logistic, and Poisson regression) with 10-fold cross-validation were employed to categorize donors based on clinical variables (age, body mass index, hypertension, expanded criteria donor kidney) and histologic scores (vascular fibrous intimal thickening, interstitial fibrosis, tubular atrophy, arteriolar hyaline thickening). Archetypal analysis and linear mixed model were applied to determine molecular phenotypes and their association with 1-year posttransplant estimated glomerular filtration rate (eGFR) in 234 donor kidneys. Three molecular archetypes were identified. The “ideal” archetype (median donor age 42 years, low Kidney Donor Risk Index [KDRI], minimal chronic histologic changes) was associated with the highest 1-year eGFR, whereas the “marginal” archetype (68 years, extensive chronic changes, high KDRI) was associated with the lowest one. The “intermediate” archetype yielded better 1-year eGFR despite donor profiles similar to the marginal group. Although KDRI predicted 1-year eGFR, adding molecular archetypes improved model performance (Akaike Information Criterion [AIC] 80.0 vs 83.7; P < .05). External validation in an independent data set (n = 174, GSE147451) confirmed the predictive value of the model. Molecular profiling of procurement biopsies may help to identify donor kidneys with higher posttransplant eGFR.
Materials and methods
This is a single-center prospective observational study. Wedge donor kidney procurement biopsies were performed at the back table between April 2021 and November 2022. In addition to histology, biopsy specimens were stored at –80 °C in RNAlater for future transcriptomics. The primary aim of the study was to create a molecular classifier of the donor kidney quality useful for posttransplant outcome prediction. A total of 12 kidney biopsies in donors after circulatory death (DCD) were assessed separately as warm ischemia before procurement may affect molecular signals. Finally, 276 kidney biopsies in 174 brain-death deceased donors were analyzed and posttransplant outcomes were available in 234 of them. The primary endpoint was 1-year estimated glomerular filtration rate (eGFR) after transplantation, calculated using the 2009 CKD-EPI equation. All biopsies were scored for vascular fibrous intimal thickening, interstitial fibrosis and tubular atrophy, and arteriolar hyaline thickening.
https://doi.org/10.1016/j.ajt.2025.09.024
Published: 5 March 2026
