Mammalian Target of Rapamycin Signal Inhibitors (imTOR) Use in First and Relapse BK Polyomavirus Nephritis (BKVN) in Renal Allograft Recipients

Abstract

Background: BK virus (BKV) nephropathy is a potential deleterious infection in renal transplant patients, with a prevalence of 2-9 % in the first year after transplantation. Minimization of immunosuppression is the most common approach, and the use of imTOR in this context has been also advocated, but rarely has been used in BKV relapse of the second graft. Patients and methods: 88 pediatric patients had been transplanted since 2006 in our centre. 5 patients had developed BKV infection (5,6%) and 3 (3,4%) BKV nephropathy. Histology showed Grade C BKV nephropathy in Patient 1, and B in Patients 2 and 3. All of them were switched to low levels of imTOR (Patients 1 and 2 to sirolimus, Patient 3 to everolimus) for a through level of 4-5 ng/ml. Patient 1 loosed the graft and Patients 2 and 3 recovered normal function with blood PCR assay less than log3,5 for BKV. Patient 1 became PCR negative after transplantectomy, but under sirolimus 4 -5 ng/ml developed reinfection in the second graft. (BKV PCR log6,5), and 1 month after blood PCR BKV was negative but developed biopsy-proven acute humoral rejection with donor specific antibodies without BKV nephropathy. Gammaglobulin and repeated plasmapheresis were given, sirolimus was maintained and cyclosporine was added. After a 6months follow-up creatinine is stable, around 2 mg/dl and BKV PCR is negative with proteinuria 1 g/24h. Conclusions: To low immunosuppression is the first step in treatment of BKV nephropathy. imTOR could be the drug of choice in this context. BKV prognosis is related to histology. Relapse of BKV could happen also after transplactectomy. Rejection could happen when immunosuppression is lowered.