Glomerular Abnormalities Associated with Chronic Calcineurin Inhibitor Nephrotoxicity in Late Renal Allograft Biopsies

Background Chronic calcineurin inhibitor (CNI) nephrotoxicity has been considered a significant risk factor for renal allograft survival. The aim of this study was to assess the association between the severity of chronic CNI nephrotoxicity and glomerular abnormalities in late renal allograft biopsies. Methods A total of 4388 renal allograft biopsies including both protocol and episode biopsies was done at the Tokyo Women’s Medical University Hospital and affiliated hospitals between January 2010 and October 2017. Among them, 245 biopsies, which were obtained more than 10 years after transplantation, was enrolled in this retrospective study. All patients were maintained under CNI-based immunosuppression. According to the severity of arteriolar hyalinosis (ah), which is a typical histologic feature of chronic CNI nephrotoxicity, the study subject was divided into two groups: biopsies with Banff ah0-1, (Group1, n=41) and biopsies with Banff ah2-3 (Group 2, n=204). Results The median time to graft biopsy in the Group 1 and Group 2 was 4749 and 5252 days, respectively. The incidence of transplant glomerulopathy (TGP) was significantly higher in the Group 2 (Group1 n=7, 18%; Group 2: n=78, 38%, p<0.01). Among the biopsies without active antibody-mediated graft injury (Banff g+ptc<2), TGP was also more observed in the Group 2 (Group 1: 3/35, 8%; Group 2: 35/155, 23%, p=0.06). Focal segmental glomerulsclerosis without other etiology such as active rejection, and recurrence and/or de novo glomerular disease was more common in the Group 2 (Group 1: n=1, 2%; Group 2: n=37, 18%, p=0.01). The average percentage of global sclerosis in the specimens was significantly higher in the Group 2 (20.6% vs 29.4%, p=0.01). Conclusions Chronic CNI nephrotoxicity was significantly associated with glomerular abnormalities including transplant glomerulopathy and glomerular sclerosis in the late renal allograft biopsies.