Protocol Biopsies Reveal Progressive Arteriolar Thickening as a Predictor of Mortality in Kidney Transplant Recipients

Kidney transplant recipients remain at high risk of cardiovascular events and premature death. Whether chronic histological changes in protocol allograft biopsies provide prognostic information for patient outcomes beyond graft survival remains uncertain. In this prospective study of 458 kidney transplant recipients with biopsies performed at 3 and 12 months and followed up to 8 years, we assessed the association between vascular and interstitial lesions and major adverse cardiovascular events (MACEs) or all-cause mortality. Fifty-eight patients (12.7%) died and 49 (10.7%) experienced MACEs during follow-up. The most notable finding was that progression of hyaline arteriolar thickening (aah) between 3 and 12 months independently predicted all-cause mortality, even after adjustment for estimated glomerular filtration rate, diabetes, and previous cardiovascular disease. In addition, vascular fibrous intimal thickening at 12 months was also independently associated with mortality, while associations of baseline vascular or interstitial lesions were attenuated after full multivariable adjustment. These results suggest that progressive aah reflects an ongoing recipient-related vascular process rather than donor-derived injury. Monitoring this dynamic histological change in repeated biopsies performed for protocol or for cause may provide transplant nephrologists with an early signal of increased mortality risk.