Clinical significance of renal biopsies showing concurrent acute rejection and tacrolimus-associated tubular vacuolization.

Abstract

The clinical significance of biopsies showing both rejection and isometric tubular vacuolization has not been well defined in the literature. The clinical picture, sequential histopathologic findings, and response to therapy were compared between 24 renal allograft biopsies showing both tubular vacuolization and rejection and 14 biopsies showing vacuolization alone. The rejection was categorized as grade 1 in 4/24 (16.6%), grade 2A in 10/24 (41.6%), and grade 2B in 10/24 (41.6%) cases (Banff schema, 1993-1995). Treatment with additional steroids and tacrolimus led to a decrease in the interstitial inflammation score (2.6+/-0.1 to 1.3+/-0.1, P<0.001), tubulitis score (2.6+/-0.1 to 1.1+/-0.1, P<0.001), and serum creatinine (4.4+/-2.2 mg/dl to 3.3+/-2.6 mg/dl, P=0.001). Complete response, partial response and no response to antirejection therapy were observed in 16/24 (66.7%), 3/24 (12.5%), and 5/24 (20.8%) patients, respectively. Although there was a rise in the plasma (1.4+/-0.2 ng/ml to 2.8+/-0.3 ng/ml, P<0.001) and whole blood (16.5+/-2.8 ng/ml to 31.2+/-5.7 ng/ml, P<0.001) tacrolimus levels, repeat biopsy showed no change in the size or extent of tubular vacuolization (mean score 2.88+/-0.19 vs. 2.83+/-0.21). The morphologic characteristics of the tubular vacuoles in these cases did not differ from those observed in 14 cases of tacrolimus nephrotoxicity not complicated by rejection. Patients with concurrent acute rejection and tubular vacuolization usually benefit from increased immunosuppression. The pathogenesis of the vacuolization in this clinical setting is not clear, but may reflect immune-mediated tubular injury.