Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

摘要: Background Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led numerous studies investigating withdrawal tapering strategies. Despite this, uncertainty remains about minimisation or of CNI. Objectives This review aimed look at the benefits harms in terms function loss, incidence episodes, treatment-related side (hypertension, hyperlipidaemia) death. Search methods We searched Cochrane Kidney Transplant Specialised Register 11 October 2016 through contact Information Specialist using search relevant this review. Studies contained identified strategies specifically designed for CENTRAL, MEDLINE, EMBASE; handsearching conference proceedings; searching International Clinical Trials (ICTRP) Search Portal ClinicalTrials.gov. Selection criteria All randomised controlled trials (RCTs) where drug regimens containing were compared alternative (CNI withdrawal, low dose) post-transplant period included, without age dosage restriction. Data collection analysis Two authors independently assessed eligibility, risk bias, extracted data. Results expressed ratio (RR) mean difference (MD) 95% confidence intervals (CI). Main results We included 83 that involved 16,156 participants. Most open-label studies; less than 30% reported randomisation method allocation concealment. analysed intent-to-treat 60% all pre-specified outcomes 54 studies. The attrition reporting bias unclear remainder factors used judge inconsistently. We also noted 50% (47 studies) funded by pharmaceutical industry. We classified into four groups: avoidance substitution mammalian target rapamycin (mTOR-I); dose mTOR-I. groups further stratified subgroups major outcomes. CNI lead (RR 2.54, CI 1.56 4.12; moderate certainty evidence), make little no death 1.09, 0.96 1.24; certainty), probably slightly reduces 0.85, 0.74 0.98; quality evidence). Hypertension was reduced group 0.82, 0.71 0.95; while malignancy 1.10, 0.93 1.30; makes cytomegalovirus (CMV) 0.87, 0.52 1.45; certainty) CNI result increased 2.16, 0.85 5.49; certainty) 0.96, 0.79 1.16; certainty). Late 3.21, 1.59 6.48; 0.84, 0.72 0.97, certainty). Results similar when combined introduction mTOR-I; 1.43; 1.15 1.78; there 0.96; 0.69 1.36, mTOR-I 0.94, 0.75 1.19; 0.86, 0.64 1.15; moderate), 0.60, 0.44 0.82; 0.69, 0.47 1.00; Lymphoceles 1.45, 0.95 2.21; certainty). Low glomerular filtration rate (GFR) (MD 6.24 mL/min, 3.28 9.119; 0.75, 0.55 1.02; made 1.13 ; 0.91 1.40; decreased 0.98, 0.80 1.20; CMV 0.41, 0.16 1.06; Low plus 1.22, 0.42 3.53; 1.16, 1.90; certainty). Authors' conclusions CNI increases least over short-term. induction events, use infections These conclusions must be tempered lack long-term data most studies, particularly regards antibody-mediated rejection, suboptimal methodological