018 Sirolimus in rescue of chronic allograft nephropathy in children: inhibition of proliferation added to less anticalcineurinic toxicity

Abstract

Sirolimus, an mTOR immunosuppressor has been used in kidney transplanted children with advantage related to no renal toxicity and antiproliferative action that could slow the course of chronic allograft nephropathy (CAN). Sirolimus has been used as de novo therapy or after conversion from anticalcineurinic (CNI) based regime, alone or combined with mycophenolic acid. Our present work suggest that in the context of CAN, sirolimus plus an anticalcineurinicin in a lesser dose and mycophenolic acid (MMF) could offer in kidney-transplanted children an immunosuppressive regime with less toxicity and even an improvement of renal function. After a follow-up period post-transplant of 6 ± 2.2 years, 12 patients that developed biopsy-proved CAN nephropathy and with a therapeutic regime based in CNI and MMF received sirolimus and a lower level (50 %) of CNI with MMF unchanged. After a follow-up of 18 months, creatinine level improved from 2.8 ± 0.56 g/100 ml to 2.2 ± 0.4 mg/100 ml (p < 0.04) in 8 patients, and was unchanged in the other 4. Proteinuria was initially 24 ± 8 mg/m 2 /h and did not show significative chages. No adverse adverse effects were registered. The rational of this approach is to establish a synergy between CNI, mTOR and MMF because the target of these immunosuppressants is different. CNI toxic effects and sirolimus infectious and wound healing problems could be also eluded, because the use of a lesser dose of CNI and delayed introduction of mTOR. Nevertheless the risk of PTLD could not change with the use of mTOR.