Is arteriolar vacuolization a predictor of calcineurin inhibitor nephrotoxicity?

Calcineurin inhibitors (CNI) have been commonly used as pivotal immunosuppressive agents to renal transplant recipients and have contributed significantly to improving short-term allograft survival. However, long-term administration of CNI may cause an adverse effect on kidney function, known as chronic nephrotoxicity. Chronic CNI nephrotoxicity (CNI-NT) shows characteristic histopathological findings that involve arteriolar hyalinosis. Recently, the term alternative arteriolar hyalinosis (aah) is used to discriminate CNI-specific arteriolar hyaline deposition from non-specific arteriolar hyalinosis. We studied whether arteriolar vacuolization represents an early lesion of aah as a predictor of CNI-NT. We retrospectively studied the 79 patients under treatment with a CNI immunosuppressant, who underwent living-related renal transplantation (RTx) from January 2007 to March 2009. We examined serial protocol graft biopsies at one h, one, six, and 12 months after RTx. We classified histological findings into two groups on the basis of aah lesion (with or without aah) in serial biopsies for 12 months. Arteriolar vacuolization was more frequently observed in the aah group than in the non-aah group with a significant difference. Arteriolar vacuolization was found even in the one-h biopsy specimens, indicating a non-specific histopathological finding. But in the aah group, arteriolar vacuolization tended to be more frequently observed later on. Aah can be a predictor of CNI-NT.