慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效观察

The curative effect of sirolimus conversion for liver transplantation patients with chronic renal injury

目的观察慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效。方法应用钙调磷酸酶抑制剂（CNI）并伴有慢性肾功能损伤的肝移植受者23例（其中19例应用他克莫司，4例应用环孢素A）转换为西罗莫司（SRL）治疗。SRL的起始剂量为4mg／d，次日为2mg／d，应用高压液相色谱法测定全血SRL浓度，当血SRL浓度达5～8μg／L后，停用CNI类药物，同时服用吗替麦考酚酯，1g／d。记录受者入组前的基础血清肌酐（cr）、肌酐清除率、肾小球滤过率（GFR），并分别于用药后第1、3、6、12和24个月时监测血SRL浓度、Cr、肌酐清除率、GFR，同时监测受者体重、血压、血细胞计数、肝功能和肝脏生化指标、血脂、尿蛋白。于用药后12个月时行肝脏穿刺活检确认有无排斥反应。结果23例平均随访29．4个月，随访期内死亡2例，另21例于用药后1、3、6、12和24月时的Cr分另U为（147．40±23．36）、（152．60±20．08）、（1S0．20±22．64）、（137．60±18．09）、（138．30±17．04）μmol／L，与cr的基础值[（158．91±29．13）μmol／L]相比较，1、12、24个月时的差异有统计学意义（P〈0．05）。用药后1、3、6、12和24月时的肌酐清除率分别为（0．97±0．18）、（0．99±0．14）、（1．00±0．17）、（1．07±0．29）、（1．14±0．12）ml／s，与基础肌酐清除率[（0．91±0．14）ml／s]相比较，1、12、24个月时的差异有统计学意义（P〈0．05）。用药后1、3、6、12和24月时的GFR分别为（0．80±0．15）、（0．78±0．11）、（0．75±0．12）、（0．84±0．10）、（0．94±0．13），与基础GFR[（0．71±0．11）ml／s]相比较,1、12、24个月时的差异有统计学意义（P〈0．05）。应用SRL后第1、3、6、12和24个月时，Cr≤123μmol／L者所占的比例分别为38．1％、33．3％、28．6％、47．6％和52．4％。随访期内无受者发生排斥反应。结论慢性肾功能损伤的肝移植受者转换为西罗莫司治疗可改善其肾功能。转换治疗未增加排斥反应的发生率。

Objective To observe the curative effect of sirolimus conversion for liver transplantation patients with chronic renal injury. Methods In 23 recipients of liver transplantation using CNI （19 cases using tacrolimus, and 4 cases using cyclosporine A） with chronic renal injury, the immunosuppressant was converted to sirolimus （SRL）. The initial dose of SRL was 4 mg per day and 2 mg at the next day. The blood SRL concentration was determined by using high pressure liquid chromatography. When the valley value of SRL concentration reached a range between 5 to 8 μg/L, CNI was withdrawn and MMF （1 g/day） was given simultaneously. The basal values of serum creatinine （Scr）, creatinie clearance rate （Ccr） and glomerular filtration rate （GFR） were recorded in the recipients before study, and at 1st, 3rd, 6th, 12th, and 24th month after using SRL, blood SRL concentration, Scr, Ccr and GFR, as well as body weight, blood pressure, blood cells count, liver function （serum bilirubin, albumin and prothrombin time）, liver biochemistry （AST, ALT, γ-GT and AKP）, blood fat （cholesterol and triglyceride） and urine protein were monitored. At the 12th month after using SRL, the graft liver was biopsied to diagnosis rejection. Results During an average follow- up period of 29. 4 months, there were two deaths. In the remaining 21 cases, the Scr values were （147.40 ± 23. 36）, （152. 60 ±20. 08）, （150. 20 ± 22. 64）, （ 137.60 ± 18. 09） and （138. 30 ± 17.04）μmol/L, respectively at 1st, 3rd, 6th, 12th, 24th month after using SRL. As compared with basal Scr values [（158. 91 ± 29. 13） μmol/L], there were statistically significant differences at 1st, 12th, 24th month （P〈0. 05）. The Ccr values were （0.97 ± 0. 18）, （0. 99 ± 0. 14）, （1.00 ±0. 17）, （1.07 ± 0. 29） and （1.14±0. 12） ml/s, respectively at 1st, 3rd, 6th, 12th, 24th month after using SRL. As compared with basal Ccr value [（0. 91 ± 0. 14） ml/s], there were statistically significant differences at 1st, 12th, 24th month （P〈0. 05）. The GFR values were （0. 80 ± 0. 15）, （0. 78 ± 0. 11）, （0. 75 ± 0. 12）, （0. 84±0. 10） and （0. 94±0. 13） ml/s, at 1st, 3rd, 6th, 12th, 24th month after using SRL. As compared with basal GFR value [（0.71 ± 0. 11） ml/s], there were statistically significant differences at 1st, 12th, 24th month （P〈0. 05）. The proportion of patients with Scr≤123μmol/L in 21 cases was 38. 1%, 33.3 %, 28. 6 %, 47. 6 % and 52. 4%, respectively at 1st, 12th, 24th month （P〈0.05）. No rejection cases were observed. Conclusion The immunosuppressant conversion to SRL improves renal function of liver transplantation patients with chronic renal injury, and the conversion cure can not cause rejection.