vv Archive of Organ Transplantation DOI CC By 01 Clinical Group Citation: Bonini ATG, Esteves ABA, Camargo LF, do Valle CF, Rivelli GG, et al. (2017) Therapy with mTOR Inhibitors in Polyomavirus Allograft Nephropathy (PVAN): A Five Year Follow Up. Arch Organ Transplant 2(1): 001-03. Case Report Therapy with mTOR Inhibitors in Polyomavirus Allograft Nephropathy (PVAN): A Five Year Follow Up Ana Theresa Guanaes Bonini, André Barros Albuquerque Esteves, Leonardo Figueiredo Camargo, Carla Feitosa do Valle, Gabriel Giollo Rivelli, Marcos Vinícius de Sousa and Marilda Mazzali* Division of Nephrology, Department of Medicine, School of Medical Sciences, University of Campinas- DCM/FCM/UNICAMP, Rua Tessalia Vieira de Camargo, Brazil Dates: Received: 15 December, 2016; Accepted: 18 March, 2017; Published: 22 March, 2017 *Corresponding author: Marilda Mazzali, Division of Nephrology, Department of Medicine, School of Medi- cal Sciences, University of Campinas- DCM/FCM/UNI- CAMP, Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, 13083-970- Campinas- Sao Paulo- Brazil, Tel: 55-19-35218204; Fax: 55-19-3521- 8208; E-mail: Keywords: Polyomavirus; mTOR inhibitor; Renal transplantation https://www.peertechz.com Introduction Polyomavirus allograft nephropathy (PVAN) is an important post-transplant complication. Despiteits low incidence, around 5%, graft loss occurs in about 50% of cases [1]. In established PVAN (stage B), reduction in immunosuppressive therapy is considered as a safe strategy, in order to retard graft loss. However, the best approach remains controversial. While some groups suggest reduction of mycophenolate doses, others consider calcineurin inhibitors withdrawal or converting therapy to mTOR inhibitors or azathioprine [2]. Experimental data showed that Polyomavirus activates mTOR pathway in epithelial tubular cells. In Polyomavirus infected tubular cells culture, sirolimus and/or leflunomide reduced the expression of BKvirus large T antigen, suppressing the infection [3]. Abstract Polyomavirus nephropathy (PVAN) has a negative impact on renal allograft survival. Therapy options include reduction of immunosuppression and antiviral drugs. Aim: Evaluate the effect ofmTORi based immunosuppression on PVAN. Methods: Cross-sectional cohort of 21 renaltransplant recipients with PVAN. Initial immunosuppression based on MPA/tacrolimus was changed to mTOR/steroids at diagnosis, if urine protein/creatinine ratio <0.5 g/l. Patients weremonitored by urine cytology, qualitative PCR in peripheral blood, serum creatinine andprotein/creatinine ratio. Results: PVAN was suspected 14.3±19.3 months post-transplant, by thepresence of decoy cells in serial urine cytology. At this point, serum creatinine was 1.4 ± 0.5 mg /dL, through levels of tacrolimus (TAC) was 8.6 ± 3.5 ng/dL. TAC dose was reduced (through level 6.8 ± 2.8 ng/dL). However, in presence of persistent viruria and allograft dysfunction (creatinine 2.5 ± 0.7 mg/dL), a biopsy was performed 30.0±18.1 months post-transplant, with the final diagnosis of PVAN stage 2. MPA and TAC were withdrawn and immunosuppressive therapy maintained with mTORi (sirolimus or everolimus) plus steroids. No rejection episodes were observed. In a 5-year follow up, 10/21 (47.6%) grafts were lost due progression of PVAN. Risk factors for graft loss were higher creatinine at first viruria (1.7 ± 0.7 versus 1.4 ± 0.4 mg/dl, p<0.05) or at biopsy (3.1 ± 0.6 versus 2.3 ± 0.7 mg / dl), compared to group with a functioning graft after 5 years. In the latter group, after 70 months of follow-up, renal function remained stable (creatinine 2.0 ± 0.5 mg/dl); with negative viruria 16 weeks post mTORi. Conclusion: In this series, the change of immunosuppression to mTORi and prednisone was safe with cleared viruria onaverage 16 weeks after conversion. In patients with earlier renal biopsy and with better renal function, this strategy preserved the allograft function. Based on these data, we hypothetized that early changes in immunosuppression to proliferation signal inhibitors (PSI- mTORi) in renal transplant patients with viruria or viremia could have a protective effect on the progression of PVAN. Local protocol consists in routine screening for Polyomavirus infection by sequential viruria (urine cytology) and conversion to mTORi (sirolimus or everolimus) at histologic confirmation of PVAN. The aim of this study was to evaluate the safety and efficacy of converting therapy to mTORi in renal transplant patients with PVAN. Patients and Methods From the renal transplant database, all patients with PVAN diagnosis were selected, and medical records analyzed for inclusion and exclusion criteria. Inclusion criteria: a) Recipients from isolated kidney.