POS-794 Conversion to sirolimus in kidney transplant patients: the main indications

Abstract

The mTOR inhibitors (Sirolimus) has been used in kidney transplantation for very specific indications, essentially in case of neoplastic complications after transplantation secondary to calcineurin inhibitors.Then, the indications have been extended.To describe the different indications of sirolimus conversion in renal transplant patients in Tunisia, we carried out a multicenter study. This is a retrospective multicentric cross-sectional and analytical study performed over a period of 30 years (from 1986 to 2017), which collected all kidney transplant patients who received mTOR inhibitors during any time of their follow-up for a minimum period of 6 months. During study period, 89 patients were collected from the different Tunisian renal transplantation units. The majority of patients came from the SAHLOUL and CHARLES NICOLLES hospitals. The average age of patients at the time of transplantation was 34.71 years. Seventy percent were male. Initial nephropathy was indeterminate in 39 % of patients. All patients received sirolimus during their post-transplant follow-up with a mean of 3.13 +/- 4.73 years. The first indication (49% of cases) of Sirolimus initiation in our study was the diagnosis of neoplastic and pre-neoplastic lesions. Neoplastic lesions were noted in 36 patients (40%) and pre-neoplastic lesions in 08 patients. The most frequent neoplasia was Kaposi's sarcoma in diagnosed in 22.5% of patients. The second indication for switching to sirolimus was calcineurin inhibitors toxicity. In fact, 21 patients in our study had received Sirolimus because of calcineurin inhibitors toxicity. Tacrolimus toxicity was noted in 13 patients (15%) and Ciclosporin toxicity was found in 08 patients (9%). On the other hand, seven patients in our study had received Sirolimus after renal transplantation because of BK virus nephritis. Two patients had presented a thrombotic micro angiopathy related to tacrolimus requiring switching to Sirolimus. One patient presented with severe leuko-neutropenia with white blood cell count of 880/mm³ and neutrophils of 150/mm³. The etiological investigation was negative. In front of persistence of this leuko-neutropenia despite decreasing and then withdrawing MMF, a switch to Sirolimus was decided. In addition, Sirolimus was administered to one patient because of a primary CMV infection that occurred after 04 months of renal transplantation and was resistant to treatment with Foscavir and Ganciclovir. Furthermore, 13 patients had been programmed to be converted to Sirolimus. The conversion was decided, in 04 cases, in front of past history of lesions providing degeneration before the transplantation. These antecedents were: villous atrophy, a colloid thyroid nodule, Bourneville's tuberous sclerosis causing degeneration of skin nodules, and a mixed germ cell tumor. In 09 patients, the systematic conversion to Sirolimus was a part of a national protocol. Conversion from calcineurin inhibitor to sirolimus is one of the major thrusts of the current development of immunosuppression in kidney transplantation. The aim is to minimize the side effects of calcineurin inhibitors and ensure better graft and patient survival. According to our study, neoplastic complications and calcineurin inhibitors toxicity are the main indications of conversion to Sirolimus in Tunisia.