Abstract

Introduction: Allograft vasculopathy (AV) defined by arterial intimal fibrosis with mononuclear cell inflammation in fibrosis and formation of neointima is one of the main limiting factors in renal graft survival. The etiopathogenesis is multifactorial, including immune mediated mechanism (chronic active or chronic ABMR or mixed ABMR/TCMR), inmune independent factors (e.g.,donnor age) and the endothelial to mesenchymal transition (ETM).The aim of this study is to evaluate the presence of transplant vasculopathy in kidney transplant biopsies, and the risk factors associated. Methods: This retrospective study included 400 allograft biopsies for cause in 294 kidney transplant recipient from 2014 to 2018. All biopsies, with and without transplant vasculopathy, donor, recipient and transplant variables were analyzed. We classified the biopsies in Early (< 3 months) and late(> 3 months).Clinical variables of the recipient were analyzed: age, antiHLA sensitization; from the donor: age, alive -deceased; optimal-marginal and transplant process: TIF, mismatch, delayed graft function (DGF); histological features: rejections, microcirculation injury, C4d. Statistical analysis: Categorical variables are reported as percentages and continuous variables as mean ± standard deviation, median or interquartile range, according to distribution. Chi square test was used to compare categorical variables and T test for continuous variables. Logistic regression models were applied to determine the association of clinical and histological factors with vasculopathy. Odds ratios (OR) with 95% CI were estimated. A p <0.05 was considered significant. The statistical package Medcalc 3.0 was used. Results: Transplant vasculopathy was found in 51,7 % (207/400) sample biopsies, 40% in the early and 60 % in the late transplant biopsies. Recipient age 46(18-76) years, 57 % men, 11,1 % sensitized and 12,2 % hypersensitized. 19,3 % had unacceptable antigens and 16,6%(49/294) developed DSA. All patients received induction and triple immunosuppression therapy. Donor age was 46 (10-73) years, 51 % males, 54,4 % deceased donors and 16, 6%(49) met expanded criteria. Mean Ischemic time was 16,7 ± hours, MM 3.5(1.4), DGF 62,3 %. Vasculopathy in early biopsies was associated with ABMR in patients with DSA. In univariate analysis transplant vasculopathy was correlated with male recipient gender (p=0,0354), staining c4d +(p=0,029) and chronic glomerulopathy (p=0,0116). Late vasculopathy was associated with c4d + p=0,0048; MVI p=0,0018; late rejection p<0.0001 and cellular rejection p=0.03. In multivariate analysis recipient gender (p=0,04) and time of rejection(p=0,03) were statistically significant. Conclusion: Transplant vasculopathy was correlated with male recipient gender, staining c4d +, and chronic glomerulopathy. Late vasculopathy was associated with c4d +, MVI, late and cellular rejection.

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