Ducloux Didier, Motte Gérard, Billerey Claude, Bresson-Vautrin Catherine, Vautrin Pierre, Rebibou Jean-Michel, Saint-Hillier Yves, Chalopin Jean-Marc
Department of Nephrology, Dialysis, and Renal Transplantation, Hôpital Saint-Jacques, 2, Place Saint-Jacques, 25030, Besançon, France.
Transpl Int. 2002 Sep;15(8):387-92. doi: 10.1007/s00147-002-0403-3. Epub 2002 Aug 21.
Because recent large studies have demonstrated that mycophenolate mofetil (MMF) is superior to azathioprine (AZA) as a post-transplant immunosuppressant, it has been speculated that MMF could have a cyclosporin (CsA)-sparing effect in renal transplant recipients with chronic allograft dysfunction. Between April 1996 and October 1998, 31 patients with chronic allograft dysfunction were assigned to have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and graft outcomes were analysed. Mean follow-up time after MMF conversion was 27+/-11 months. Serum creatinine concentration (sCt) significantly decreased after conversion and remained stable at the end of follow-up (227+/-31 micro mol/l vs. 185+/-50 micro mol/l; P<0.0005). Mean variation in sCt was -24% after conversion, whereas it was +20% in the year before conversion ( P<0.001). There was a significant inverse relationship between proteinuria at baseline and improvement in renal function (r=-0.35; P=0.01). Proteinuria increased during follow-up (0.79+/-0.6 vs. 1.79+/-1.08 g/day; P=0.04). Isolated CsA nephropathy was associated with the best outcome. Renal function significantly improved in patients with grade 1 chronic rejection and remained stable in patients with grade 2 chronic rejection. Two patients (6.5%) experienced late acute rejection, respectively 13 and 24 months after CsA withdrawal. Eight patients (29%) experienced systemic infections requiring hospitalization. Blood pressure control and lipid profile improved after conversion. CsA withdrawal with a concomitant switch from AZA to MMF allows a substantial and durable improvement in renal function. Both allograft histology and proteinuria at baseline are predictive of the evolution of renal function after conversion. Physicians should consider the risk of over-immunosuppression possibly associated with this therapeutic strategy.
由于近期的大型研究表明,霉酚酸酯(MMF)作为移植后免疫抑制剂优于硫唑嘌呤(AZA),因此有人推测,MMF对患有慢性移植物功能障碍的肾移植受者可能具有环孢素(CsA)节省效应。在1996年4月至1998年10月期间,31例患有慢性移植物功能障碍的患者被安排从AZA转换为MMF,并同时停用CsA。对患者和移植物的结局进行了分析。MMF转换后的平均随访时间为27±11个月。转换后血清肌酐浓度(sCt)显著降低,并在随访结束时保持稳定(227±31微摩尔/升对185±50微摩尔/升;P<0.0005)。转换后sCt的平均变化为-24%,而转换前一年为+20%(P<0.001)。基线蛋白尿与肾功能改善之间存在显著的负相关(r=-0.35;P=0.01)。随访期间蛋白尿增加(0.79±0.6对1.79±1.08克/天;P=0.04)。孤立性CsA肾病的结局最佳。1级慢性排斥反应患者的肾功能显著改善,2级慢性排斥反应患者的肾功能保持稳定。两名患者(6.5%)分别在停用CsA后13个月和24个月发生迟发性急性排斥反应。八名患者(29%)发生需要住院治疗的全身感染。转换后血压控制和血脂情况有所改善。停用CsA并同时从AZA转换为MMF可使肾功能得到实质性且持久的改善。移植肾组织学和基线蛋白尿均可预测转换后肾功能的演变。医生应考虑这种治疗策略可能带来的免疫抑制过度风险。