Knoll Greg A, MacDonald Ian, Khan Asmat, Van Walraven Carl
Division of Nephrology, Kidney Research Centre, and Department of Medicine, University of Ottawa, and Clinical Epidemiology Unit, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
J Am Soc Nephrol. 2003 Sep;14(9):2381-6. doi: 10.1097/01.asn.0000079616.71891.f5.
Mycophenolate mofetil (MMF) significantly decreases acute rejection rates after renal transplantation, but intolerance often occurs, leading to dose reduction. The clinical effect of MMF dose reduction has not been clearly established. This study determined whether MMF dose reduction after renal transplantation was associated with subsequent risk of acute rejection. This retrospective cohort study assessed 213 renal transplant recipients. Cox regression was used to model MMF dose as a time-dependent variable, with time to first acute rejection as the primary outcome. One hundred twenty-six patients (59%) had a total of 176 MMF dose reductions during the study. MMF dose was reduced because of leukopenia (55.1%), gastrointestinal symptoms (22.2%), infection (7.4%), malignancy (1.1%), and unknown reasons (14.2%). The cumulative number of days with the MMF dose reduced below full dose was an independent predictor of acute rejection. The relative risk of rejection increased by 4% for every week that the MMF dose was reduced below full dose. No significant association was observed between the number of days with MMF dropped below full dose and allograft failure. The cumulative number of days with the MMF dose dropped below full dose is a significant predictor of acute rejection after renal transplantation. Clinicians need to be aware of the rejection risk when the MMF dose is reduced and maintain close surveillance on such patients.
霉酚酸酯(MMF)可显著降低肾移植术后急性排斥反应的发生率,但常出现不耐受情况,导致剂量减少。MMF剂量减少后的临床效果尚未明确。本研究旨在确定肾移植术后MMF剂量减少是否与随后的急性排斥反应风险相关。这项回顾性队列研究评估了213名肾移植受者。采用Cox回归将MMF剂量作为时间依赖性变量进行建模,将首次发生急性排斥反应的时间作为主要结局。126例患者(59%)在研究期间共进行了176次MMF剂量减少。MMF剂量减少的原因包括白细胞减少(55.1%)、胃肠道症状(22.2%)、感染(7.4%)、恶性肿瘤(1.1%)以及不明原因(14.2%)。MMF剂量降至全剂量以下的累计天数是急性排斥反应的独立预测因素。MMF剂量降至全剂量以下每持续一周,排斥反应的相对风险增加4%。未观察到MMF剂量降至全剂量以下的天数与移植肾失功之间存在显著关联。MMF剂量降至全剂量以下的累计天数是肾移植术后急性排斥反应的重要预测因素。临床医生在MMF剂量减少时需要意识到排斥反应风险,并对这类患者进行密切监测。