西罗莫司替代钙调磷酸酶抑制剂治疗肾毒性和慢性移植肾肾病

Sirolimus alternative for calcineurin inhibitor in treatment of nephrotoxicity and chronic allograft nephropathy

背景:西罗莫司替代钙调磷酸酶抑制剂治疗肾移植后钙调磷酸酶抑制剂肾毒性和慢性移植肾肾病,转换对象的选择和时机至关重要。目的:观察不同血肌酐水平下应用西罗莫司替代钙调磷酸酶抑制剂治疗肾移植患者钙调磷酸酶抑制剂肾毒性和慢性移植肾肾病的临床效果。方法:选择肾移植后确诊钙调磷酸酶抑制剂慢性肾毒性和慢性移植肾肾病患者,根据转换前血肌酐≤220μmol/L和血肌酐>220μmol/L,各分为钙调磷酸酶抑制剂肾毒性组、慢性移植肾肾病组和钙调磷酸酶抑制剂维持组;前两组将原有免疫抑制方案中钙调磷酸酶抑制剂转换为西罗莫司,转换组共53例,钙调磷酸酶抑制剂维持患者为对照组共28例,随访3年。动态观察各组在不同随访时间点的血肌酐水平及不良事件发生率,并在随访终点共行移植肾穿刺活检9例。结果与结论:转换前血肌酐≤220μmol/L钙调磷酸酶抑制剂肾毒性组、慢性移植肾肾病组血肌酐值,在随访第24、36个月血肌酐较转换前明显降低(P<0.05),钙调磷酸酶抑制剂维持组血肌酐呈缓慢爬行上升高于前两组(P<0.05)。血肌酐>220μmol/L钙调磷酸酶抑制剂肾毒性组血肌酐转换后显著下降(P<0.05);后两组转换后血肌酐呈爬行上升(P<0.05)。转换后主要不良事件有轻度贫血(30.2%)、高脂血症(35.8%)、白细胞低下(22.6%)等。肾移植后血肌酐爬行升高转换西罗莫司方案疗效显著,转换前穿刺活检确诊钙调磷酸酶抑制剂肾中毒还是慢性移植肾肾病,并结合血肌酐水平综合判断是否行西罗莫司转换治疗,注意监测血脂水平;转换应在移植肾功能发生严重损害前进行,早期转换,患者将获益更大。

BACKGROUND： Sirolimus alternative for calcineurin inhibitor therapy is used for calcineurin inhibitor nephrotoxicity and chronic allograft nephropathy after renal transplantation. Conversion object selection and timing are essential. OBJECTIVE： To observe the clinical effects of sirolimus alternative calcineurin inhibitor in the treatment of renal transplant patients with calcineurin inhibitor nephrotoxicity and chronic allograft nephropathy under different serum creatinine levels. METHODS： Chronic calcineurin inhibitor nephrotoxicity and chronic allograft nephropathy patients, who were diagnosed after renal transplantation, were enrolled. In accordance with serum creatinine ≤ 220 μmol/L and serum creatinine 〉 220 μmol/L before transition, they were divided into calcineurin inhibitor nephrotoxicity group, chronic allograft nephropathy group and calcineurin inhibitor maintenance group. In the former two groups, calcineurin inhibitor was converted into sirolimus （conversion group, n=53）. Calcineurin inhibitor maintenance patients served as control group （n=28）. Follow-up was done for 3 years. Serum creatinine levels and the incidence of adverse events were dynamically observed in each group at different follow-up time points. Nine cases underwent the transplanted kidney biopsy at the end of the follow-up. RESULTS AND CONCLUSION： Before conversion, under serum creatinine ≤ 220 μmol/L, serum creatinine levels were significantly lower at 24 and 36 months after follow-up in the calcineurin inhibitor nephrotoxicity group and chronic allograft nephropathy group （P 〈 0.05）. Serum creatinine levels were higher in the calcineurin inhibitor maintenance group than that in the chronic allograft nephropathy group and calcineurin inhibitor nephrotoxicity group （P 〈 0.05）. Under serum creatinine 〉 220 μmol/L, serum creatinine levels were significantly reduced in the calcineurin inhibitor nephrotoxicity group after conversion （P 〈 0.05）. Serum creatinine levels were increased in the chronic allograft nephropathy group and calcineurin inhibitor maintenance group after conversion （P 〈 0.05）. After conversion, major adverse events included mild anemia （30.2%）, hyperlipidemia （35.8%）, and leukopenia （22.6%）. After renal transplantation, a significant effect was detected in elevated serum creatinine crawling conversion sirolimus program. Pre-conversion biopsy diagnosed calcineurin inhibitor nephrotoxicity or chronic allograft nephropathy. In combination of serum creatinine levels, we comprehensively judged whether sirolimus conversion therapy was performed or not. Blood lipid levels were monitored. The conversion should be conducted before severe damage occurred in transplanted kidney, i.e., early conversion. The patients will benefit more.