Results of Immunosuppressive Switch in Polyoma Virus Nephropathy in Immunologically High Risk Kidney Transplant Recipients

Abstract

Introduction: Polyoma virus nephropathy is one of the most dreadful complications after kidney transplantation and usually results in graft lost and jeopardizes the future possibility of re-transplantation. Here we present the results of five kidney transplant recipients (KTRs) who developed polyoma virus nephropathy (BKVN) within the first six months after living-related kidney transplantation (LRKT) and were switched to a new immunosuppressive regimen consisting of: low dose cyclosporin, low dose everolimus and reduced dose of antimetabolites. Methods: Four KTRs were men and one was a woman with an average age of 46 years. All were immunologically high risk KTRs with an average HLA mismatch of 4 and were transplanted their first grafts from living-related donors. All of them had received ATG (Fresenius S) and methylprednisolone (500 mg/day) as an induction therapy. The maintenance immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil (2 gm/day) and prednisolone (tapered from 40 mg/day to 5 mg/day within 6 weeks). Tacrolimus trough levels were monitored in all patients. All patients also received valganciclovir (900 mg/day) and TMP-SMX (400 mg/day) for prophylaxis. None of the recipients were diabetic but two of them developed NODAT and were receiving insulin treatment (HbA1C's %7.1 and 6.7). Results: Average time for BKVN after transplantation was 164 days. The initial presentation of the BKVN was an increase in serum creatinine levels (average increment from the baseline = 0.7 mg/dL) and CRP levels (average increment rate % 18). Mild proteinuria (< 500 mg/L) was detected in two patients. Average trough tacrolimus level was 9.8 mg/mL). The patients underwent graft biopsy and the biopsy samples were analyzed by a nephropathologist with light microscopy and immunofluorescent stainings. After receiving the initial pathology results, urine and plasma BKV PCRs were measured. Biopsies revealed BKVN with varying degrees of tubulointerstitial inflammation and all stained for SV40. Average plasma BKV copies were 800.000 copies/mL and urinary BKV copies were 160 million/mL. The average serum creatinine level was 1.8 mg/dL at the time of diagnosis. Tacrolimus was discontinued, MMF dose reduced to 1 gm/day and prednisolone dose was reduced to 5 mg/day immediately after diagnosis. Treatment with ciclosporin-A neoral 75 mg b.id. and everolimus 0.5 mg bid was initiated. Conclusion: Average follow-up period after this immunosupressive switch was 4 months. There was an initial increase in CRP and serum creatinine levels (average increase 0.3 mg/dL) after new regimen. The serum creatinine levels didn't return to baseline value but remained stable for four months for all of the patients. The average serum creatinine levels were 1.96 mg/dL at the end of four months. There was no graft loss and evidence of systemic polyoma virus infection. Although the follow-up period is brief and the number of patients in the study are insufficient, these preliminary findings suggest that low dose ciclosporin A and everolimus combination may prevent graft loss and rejection in immunologically high risk KTRs who develop BKVN in the early course after transplantation.