慢性移植肾肾病的临床病理学特点与免疫抑制剂转换治疗

The clinical pathological characteristics and immunosuppresant conversion treatment of chronic allograft nephropathy

目的探讨慢性移植肾肾病(CAN)的病理学特点与临床应对策略。方法对20例临床诊断为慢性移植肾功能减退、病理诊断为CAN者的病理资料进行系统分析,依据Banff97标准对肾小球硬化、间质纤维化、肾小管萎缩及小动脉内膜炎等CAN特征性表现进行综合评分后,做出病理诊断和分层分析。20例肾移植后采用以环孢素A(CsA)为基础的免疫抑制方案,诊断为CAN后,3例转换为他克莫司(FK506)与霉酚酸酯(MMF)联用,17例转换为西罗莫司(Sir)与MMF联用,比较转换治疗前后肾功能的变化。结果9例(45%,9/20)合并发生亚临床排斥反应,激素冲击治疗有效;20例均存在间质纤维化、肾小管萎缩与肾小球硬化。慢性移植肾功能减退对转换治疗的反应与间质纤维化和肾小管萎缩的程度无明显相关性,但与肾小球硬化率密切相关,肾小球硬化率低于30%者预后良好,超过50%者移植肾功能丧失。结论肾小球硬化率有可能成为判断CAN病变程度和预后的指标;治疗慢性移植肾功能减退时应重视合并发生的亚临床排斥反应,撤除CsA、采用Sir与MMF联用方案值得推荐。

Objective To explore the clinical pathological characteristics and the immunosuppressant conversion treatment on chronic allograft nephropathy （CAN）. Methods Twenty cases of CAN diagnosed clinically received biopsy and then pathological evaluation based on Banff 97 schema according to glomerulosclerosis, interstitial fibrosis, tubular atrophy and arteriopathy. All cases had received cyclosporine （CsA）-based immunosuppressive protocol. Three cases were converted into tacrolimus （FK506）-based protocol and 17 into sirolimus （Sir）-based protocol. The changes in renal function were compared before and after conversion. Results Twenty cases suffered from CAN characterized by glomerulosclerosis, interstitial fibrosis and tubular atrophy. Subclinical rejection was present in 9 of them and was responsive by high-dose methylprednisolone bolus treatment. The graft function and the treatment outcome were not correlated with the severity of interstitial fibrosis and tubular atrophy, meanwhile the cases with less than 30% glomeruloscelrosis enjoyed relatively good prognosis but more than 50 % glomerulosclerosis indicated graft loss soon. Combined with mycophenolate mofetil （MMF）, basic immunosuppressant conversion of CsA to Sir or FKS06 resulted in decreased or stable blood creatinine. Conclusion The rate of glomerulosclerosis may evaluate the severity and the prognosis of CAN. The treatment protocol of CAN consists of reversion of subclinical rejection, CsA withdrawl and combined therapy of Sir and MMF.