Background: Subclinical inflammation in stable renal allografts observed in surveillance biopsies is associated with IF/TA progression and de novo HLA donor specific antibodies (DSA). Maintenance immunosuppression has been associated with subclinical inflammation being lower in patients treated with tacrolimus and MMF. However, the relationship between tacrolimus/MMF exposure and sublcinical inflammation has not been widely explored.
Patients and Methods: We analyze a prospective cohort of early surveillance biopsies (3-6 months) performed in 131 low immunological risk renal transplants treated with tacrolimus and MMF. Surveillance biopsies were evaluated according to the last update of Banff classification. We analyze the relationship between subclinical inflammation (i-Banff score >1) and clinical variables. To evaluate exposure to tacrolimus, time-concentration area under the curve (AUC; ng/mL/day) at different time points before performing the biopsy (AUC-TAC_0-1 month, AUC-TAC_1-2 months; AUC-TAC_2-3 months and AUC-TAC_3 months-biopsy) and the coefficient of variation of tacrolimus trough levels until biopsy were estimated. To evalaute exposure to MMF, AUC of MMF dose at the same time periods was estimated.
Results: Sublcinical inflammation was observed in 34 out of 131 biopsies (25.9%). In the univariate analysis subclinical inflammation was associated with patient age, HLA-DR mismatches, early steroid withdrawal, time of biopsy, AUC-TAC_2-3 months, AUC-TAC_3 months-Bx and coefficient of variation of TAC levels until biopsy. By logistic regression analysis independent variables associated with subclinical inflammation were: AUC-TAC_3 months-Bx (OR:0.64, p=0.005), HLA-DR mismatches (OR:2.09, p=.043) and early steroid withdrawal (OR:21, p=0.004).
Conclusions: Subclinical inflammation in early surveillance biopsies  is associated with low TAC exposure few weeks before biopsy, steroid free regimens and in  high HLA-DR mismatches.