The effect of the addition of mTOR (mammalian target of rapamycin) inhibitors to immunosuppression treatment in BK virus infection in renal transplant recipients

The frequency of BK virus (BKV) infection in renal transplant recipients has increased in recent years and BK virus nephropathy (BKVN) is an important problem in terms of graft function and graft survival. The most effective method in the treatment of BKV infection is to detect early viral replication with screening methods and to reduce immunosuppression. However, caution should be exercised as rapid reduction of immunosuppressive therapy may lead to an acute rejection risk. There are publications in recent years indicating that replacing the immunosuppressive treatments of patients with BK viremia and BKVN with the mTOR inhibitor reduces viremia and increases graft survival. In this study, it is aimed to retrospectively examine the effect of adding mTOR inhibitors to the immunosuppression treatment of patients with BK viremia; over BK viremia and BKVN course. The results to be obtained are intended to be guiding in terms of future treatment protocols. Between January 2010 and June 2019, the records of 2028 patients who underwent renal transplantation at Akdeniz University Faculty of Medicine Organ Transplantation Center and followed up were examined and 86 patients with BK viremia were included in the study. The information of the patients before and after the transplantation period were reached via the hospital information management system MIA-MED and organ transplantation follow-up files. The data of patients included in the study were analyzed as divided into 3 groups as TAC+EVL+CS / TAC+MMF(50%)+CS / TAC+CS (n=51, n=27, n=8, respectively) according to the immunosuppressive treatment protocols applied after detection of BK viremia. There was no significant difference between the treatment groups in terms of demographic data such as age, gender and CKD etiology (p>0,05). When the treatment responses determined according to the number of BKV copies are examined, the "full response" rate is lower in the patients receiving TAC+EVL+CS compared to the other treatment groups (%25,5, %51,9, %87,5, respectively), and the "partial response" rates are partially similar to the patients receiving the TAC+MMF(50%)+CS (%37,3, %29,6, respectively), the rate of "unresponsive to treatment" was higher in the patient group receiving TAC+EVL+CS compared to other treatment groups (%37,3, %18,5, %12,5, respectively) (p<0,05). When BKV titers were evaluated comparatively between groups, TAC+EVL+CS was found to be higher in the patient group given (p<0,05). It was thought that this difference occurred due to the significantly higher BKV titers at the time of diagnosis in the group given TAC+EVL+CS. When the patients who were determined to be "unresponsive to treatment" according to the number of BKV copies were evaluated separately; BKV titers did not differ significantly between treatment groups (p>0,05). In addition, when the time-dependent change of BKV titers was evaluated for each treatment group during the 12-month follow-up period, a statistically significant decrease in BKV titers was found in all treatment groups; including the group given TAC+EVL+CS (p<0,05). When the treatment response rates determined according to serum creatinine values are analyzed, the results between TAC+EVL+CS and TAC+MMF(50%)+CS groups were similar (p>0,05); the rate of "responsive to treatment" patients was found to be significantly lower in the group given TAC+CS (%88,2, %85,2, %50,0, respectively) (p<0,05). The limitations of our study are that; single-centered and retrospective design, the small number of patients examined, the number of patients not homogenously distributed among the treatment groups, and the duration of follow-up was limited to 12 months after the detection of BK viremia. Considering the results of our study, it is suggested that the addition of mTOR inhibitors to immunosuppression therapy in BK virus infection in renal transplant recipients may be an effective and safe treatment alternative. However, randomized controlled studies with more patients are needed to evaluate this subject with stronger data and analysis. Key Words: Renal Transplantation, BK Virus, BK Virus Nephropathy, BKVN, mTOR Inhibitors, Everolimus