Abstract

Abstract Background and Aims Despite offering superior outcomes for patients with end-stage kidney disease, kidney transplantation poses significant cardiovascular risks. Recently, histopathological findings in chronic kidney disease patients have been associated with all-cause mortality and cardiovascular events, but there is scant data on this subject in kidney transplant recipients. This study assesses the relationship between histopathological findings in protocol biopsies of kidney grafts and cardiovascular events, graft loss, and mortality in renal transplant recipients. Method A prospective observational study included 530 renal transplant recipients at the Hospital Clínic de Barcelona from March 2015 to 2019, with follow-up until March 2023. Data included demographics, comorbidities, laboratory tests, and protocol allograft biopsies at 3 and 12 months post-transplant. Associations between histopathological findings and outcomes (cardiovascular events, graft loss, mortality) were analyzed. Results Chronic vascular lesions (CV) were significantly correlated with cardiovascular death and major adverse cardiovascular events (MACE) (OR 10.4 (1.6–66.4); p 0.002). Arteriolar hyalinosis and interstitial fibrosis were independently associated with all-cause mortality (OR 4.9 (1.1-21.4); p 0.02, and 1.2 (1.03-1.3), p 0.005; respectively) regardless of the estimated glomerular filtration rate (eGFR). Associations were also found between pre-transplant factors (diabetes, hypertension, hyperphosphatemia), active smoking, and deceased donors. Notably, post-transplant hypophosphatemia was related to MACE, suggesting a potential association with malnutrition though, this subject requires further investigation. Conclusion Histopathological findings in early protocol biopsies of kidney grafts, especially chronic vascular lesions, arteriolar hyalinosis, and interstitial fibrosis, have a potential predictive value for cardiovascular events, mortality, and graft outcomes in transplant recipients, irrespective of eGFR. These insights emphasize the importance of timely post-transplant histological assessments for risk stratification and personalized interventions. Prospective studies are imperative to validate these findings and improve customized care strategies in this population.

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