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A Novel, Semiquantitative, Clinically Correlated Calcineurin Inhibitor Toxicity Score for Renal Allograft Biopsies

Neeraja Kambham^*, Suja Nagarajan, Sheryl Shah, Li Li, Oscar Salvatierra, and Minnie M. Sarwal

Departments of ^* Pathology, Pediatrics, and Surgery, Stanford University Medical Center, Stanford, California

Address correspondence to: Dr. Neeraja Kambham, Department of Pathology, Room H2110, 300 Pasteur Drive, Stanford, CA 94305-5324. Phone: 650-725-5193; Fax: 650-725-7409; E-mail: nkambham{at}stanford.edu or Dr. Minnie Sarwal, Department of Pediatrics, G306, 300 Pasteur Drive, Stanford, CA 94305-5304. Phone: 650-723-7903; Fax: 650-497-8614; E-mail: msarwal{at}stanford.edu

Calcineurin inhibitor toxicity (CNIT) is an important cause of chronic allograft nephropathy (CAN), but clinically relevant, diagnostic pathologic criteria remain to be defined. A semiquantitative, clinically correlative CNIT scoring system was developed and validated by pathologic analyses of 254 renal transplant biopsies that were obtained from 50 consecutive pediatric renal transplant recipients. Differentially weighted pathologic criteria (glomerulosclerosis, tubular atrophy, arteriolar medial hyaline, and tubular isometric vacuolization) contributed to the composite CNIT model score. Unlike other established pathology chronicity scores, such as the chronic allograft damage index, Banff, and modified Banff, the CNIT score was highly correlated with future graft function. The 3-mo CNIT score correlated significantly with 12 mo (P = 0.021) and 24 mo (P = 0.03) calculated creatinine clearance. Arteriolar medial hyalinosis seems to be the most important factor contributing to the clinical impact of the CNIT score.