5%; P < .05) [75]. A US OPTN database review of 48,292 KTxRs [35] reported that the risk of treatment for BKV replication was increased in those discharged on maintenance steroids versus those that were not (adjusted hazards ratio 1.16 (95% Paclitaxel Microtubule Associat CI 1.02, 1.31); P = .0237)). None of these studies reported on whether immunological risk status and immunosuppression target levels differed between groups. However, the study of Dadhania et al. [67] used multivariable logistic regression analysis to account for the effects of antihuman thymocyte globulin (ATG) induction, tacrolimus trough levels, tacrolimus and MMF dose and acute rejection, while the database review [35] fitted a Cox proportional hazards model to account for a very large number of possible confounding variables. 2.2.3.

Calcineurin Inhibitor-Free, Mammalian Target of Rapamycin (mTOR-) Based Regimens and Risk of BKV Replication BKVAN has been uncommonly observed in patients receiving calcineurin inhibitor-free or mTOR-based regimens. A small case series reported the development of BKVAN in 3 KTxRs maintained on sirolimus, prednisolone, and MMF [76]. None had been previously exposed to calcineurin inhibitors or experienced prior rejection. Two had received interleukin-2 antagonist induction therapy, while one had received thymoglobulin. A retrospective study reported nine cases of BKVAN in 344 kidney and 34 pancreas-kidney transplant recipients treated with sirolimus-based immunosuppression (cyclosporine-sirolimus in 6 recipients, tacrolimus-sirolimus in 1 recipient, MMF-sirolimus in 1 recipient, and cyclosporine-MMF-sirolimus in 1 recipient) [77].

Eight of nine patients had been previously exposed to ATG, while 3 had experienced acute rejection. In the US OPTN database review [35], 5380 of 48,292 KTxRs were discharged on mTOR-based immunosuppression, of whom 83 (1.74%) received treatment for BKVAN within 2 years of transplant. Multivariable analysis showed a reduction in risk of treatment for BKV replication with use of an mTOR at discharge, as compared to no mTOR use (adjusted hazards ratio 0.69 (95% CI 0.54, 0.89); P = .0048)). 2.2.4. Lymphocyte Depleting Therapy and Risk of BKV Replication The majority of studies have shown an increase in BKV replication following use of lymphocyte depleting agents for induction or treatment of rejection. This is not surprising given the immunosuppressive potency of these agents.

In a study of 120 KTxRs, multivariable analysis showed an independent influence of ATG induction on risk of BKV replication (odds ratio 5.83 (95% CI 1.60, 21.35); P = .008) [67]. Similarly, in the retrospective study of 344 kidney and 34 pancreas-kidney transplant recipients mentioned above [77], multivariable analysis correlated Dacomitinib exposure to ATG for either induction or rejection treatment with a higher incidence of BKVAN (3.53% versus 1.44%; P = .