环孢素A转换为他克莫司对慢性移植肾肾病患者的治疗效果

Effect of conversion from cyclosporine A to tacrolimus on the patients with chronic allograft nephropathy

目的探讨由环孢素A（CsA）转换为他克莫司（Tac）为主的免疫抑制方案对慢性移植肾肾病（CAN）患者的治疗效果。方法选择接受同种肾移植后发生CAN的患者153例，患者肾移植后均采用CsA、吗替麦考酚酯（MMF）及泼尼松（Pred）的免疫抑制方案。根据是否以Tac替换CsA将患者分为两组。（1）CsA组：45例，进入研究后患者维持原免疫抑制方案。（2）Tac组：108例，进入研究后将CsA转换为Tac，停用CsA后立即开始服用Tac，MMF和Pred的用法同CsA组。对所有患者随访12个月，观察人／移植。肾存活率、急性排斥反应发生率、移植。肾功能、24h尿蛋白定量、移植肾穿刺病理学活检及免疫抑制剂的不良反应等指标。结果随访12个月时，CsA组和Tac组患者存活率均为100％，移植肾存活率分别为86．6％和93．5％（P〈0．05）；急性排斥反应发生率分别为4．4％（2／45）和3．7％（4／108）（P〉0．05），6例发生急性排斥反应的患者均经甲泼尼龙冲击治疗3d后逆转。Tac组患者移植肾功能明显改善，并且出现重度蛋白尿、重度肾间质纤维化和肾小管萎缩的患者比例较CsA组显著减少（P〈0．05）。Tac组有13．8％（15例）的患者出现轻度血糖增高，发生率显著高于CsA组的4．4％（2例）（P〈0．05）；Tac组有22．2％（24例）的患者发生高血压，发生率显著低于CsA组的55．6％（25例）（P〈0．05）；17例因使用CsA而出现牙龈增生和多毛症者，经转换治疗后，症状均明显好转。结论由CsA转换为Tac为主的免疫抑制方案能够显著改善CAN患者的移植肾功能，延缓CAN的发展，转换过程中未发生严重Tac不良反应并且改善了使用CsA时出现的不良反应。

Objective To investigate the effect of conversion from cyelosporine A （CsA） to tacrolimus （Tac） on chronic allograft nephropathy （CAN）. Methods 153 CAN patients undergoing kidney transplantation received CsA, mycophenolate mofetil （MMF） and prednisone （CsA-MMF- Pred） regimen after kidney transplantation, and divided into 2 groups according to whether CsA were maintained in the immunosuppressive regimen： CsA＋ MMF＋ Pred group （CsA group, n = 45） ; Tae ＋MMF＋ Pred group （Tac group, n = 108）. The patients were followed up with patient/kidney survival rate, acute rejection incidence, renal function, 24-h proteinuria and adverse events of immunosuppressive drugs for 12 months. Results Compared with CsA group, the transplanted kidney survival rate was significantly higher in Tac group （93.5 % vs 86. 6 %, P〈0. 05）. Acute rejection （AR） was diagnosed in 4. 4 % （2/45） of recipients in CsA group and 3.7%（4/108） in Tac group （P〈0. 05） respectively. Acute rejection （2 cases in CsA group and 4 in Tac group） was reversed by 500 mg of methylprednisolone for consecutive 3 days, and the patients in Tac group showed a significantly lower degree of interstitial fibrosis and tubular atrophy （IF/TA） （P〈0. 05）. Renal allograft functions and 24-h proteinuria during a follow-up period of 12 months were significantly improved in Tac group （P% 0. 05）. Incidence of mild hyperglycemia in Tac Group （13.8 %, 15/108） was significantly higher than in CsA group （4.4 %, 2/45）, and that of hypertension in Tac group （22. 2 %, 24/108） was significantly lower than in CsA group （55. 6 %, 25/45）. CsA-related side effects （such as hirsutism and gingival hypertrophy） in 17 patients were greatly improved after conversion from CsA to Tac treatment. Conclusion The conversion from CsA to Tac on the patients with CAN can improve renal allograft function, retard the progression of renal allograft dysfunction, reduce the incidence of CsA-related side effects and not generate serious adverse effects of Tac.