Clinical significance of renal biopsies showing concurrent acute rejectionand tacrolimus-associated tubular vacuolization

Background. The clinical significance of biopsies showing both rejection an d isometric tubular vacuolization has not been well defined in the literatu re. Methods. The clinical picture, sequential histopathologic findings, and res ponse to therapy were compared between 24 renal allograft biopsies showing both tubular vacuolization and rejection and 14 biopsies showing vacuolizat ion alone. Results. 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), t ubulitis 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 respo nse 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 who le 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 vacuolizat ion (mean score 2.88+/-0.19 vs. 2.83+/-0.21), The morphologic characteristi cs of the tubular vacuoles in these cases did not differ from those observe d in 14 cases of tacrolimus nephrotoxicity not complicated by rejection. Conclusion. Patients with concurrent acute rejection and tubular vacuolizat ion usually benefit from increased immunosuppression, The pathogenesis of t he vacuolization in this clinical setting is not clear, but may reflect imm une-mediated tubular injury.