Calcineurin inhibitor sparing in paediatric solid organ transplantation : managing the efficacy/toxicity conundrum.

摘要: Despite their efficacy, the calcineurin inhibitors (CNIs) ciclosporin and tacrolimus carry a risk of debilitating adverse effects, especially nephrotoxicity, that affect long-term outcome survival children who are given organ transplants. Simple reduction in dosage CNI has little or no benefit on complete withdrawal without threatening graft may only be possible after liver transplantation. Until last decade, option was to increase corticosteroid and/or azathioprine doses, which imposed additional hazards. Considered here emerging generation new agents offering an opportunity for improving survival, minimizing CNI-related events ensuring patient well-being. A holistic, multifaceted strategy need considered — initial selection optimized use monitoring immunosuppressant regimens, early recognition indicators dysfunction, and, where applicable, introduction CNI-sparing regimens facilitating withdrawal. The evidence reviewed supports these approaches but remains far from definitive paediatric solid Because de novo immunosuppression uses more than 93% patients, effects focused sparing recurring theme sirolimus mycophenolate mofetil have been used this purpose is importance limit damage provide benefit: example, renal function critically reflects at 1 year post-transplant. While mycophenolic acid shows advantages over preserving because latter associated with proteinuria, appears potent also impairs wound healing. CNI-free depleting non-depleting antibodies plus needs much wider investigation achieve acceptable rejection rates conserve function. alternative immunosuppressants, particularly dyslipidaemia sirolimus, minimized avoid replacing one set (from CNIs) another. we can conjecture judicious combinations second novel immunosuppressants currently development will solutions, rationale low-dose therapy multiple acting by complementary mechanisms seems hold promise efficacy minimal toxicity until vision tolerance achieves reality.