接受老龄亲属活体供肾移植者采用小剂量西罗莫司的近期临床观察

Short-term clinical observation of low-dose sirolimus in living relative kidney transplantation from elderly donor

目的为降低老龄活体供肾移植后免疫抑制剂对移植肾的毒性作用,探讨应用小剂量西罗莫司的临床效果及其对移植肾的影响。方法19例亲属活体供肾移植,供者的年龄均超过55岁,受者的年龄均在30岁以下。9例肾移植后采用小剂量西罗莫司、霉酚酸酯(MMF)及泼尼松(Pred)联合用药预防急性排斥反应,10例采用环孢素A(或他克莫司)、MMF(或硫唑嘌呤)及Pred联合用药预防急性排斥反应。两种用药方案者在供、受者年龄方面的差异无统计学意义。统计术后1年、2年、3年时的血肌酐平均值,爬行肌酐的发生率,排斥反应发生率,不良事件发生率,慢性移植肾肾病(CAN)发生率。结果术后1年、2年、3年,采用小剂量西罗莫司者的血肌酐水平低于使用环孢素A(CsA)或他克莫司(FK506)者,其术后2、3年时的血肌酐水平明显低于使用CsA或FK506者(P<0.05)。使用西罗莫司者高尿酸血症发生率为11.1%,而使用CsA或FK506者这一比例为40.0%,差异有统计学意义(P<0.05);使用西罗莫司者爬行肌酐及慢性移植肾肾病的发生率均为11.1%,使用CsA或FK506者均为30.0%,差异有统计学意义(P<0.05);二者在急性排斥反应、肾功能恢复延迟、少尿、蛋白尿、血尿等不良事件发生率方面的差异无统计学意义。结论对于老龄活体供肾,移植后受者采用小剂量西罗莫司联合霉酚酸酯、泼尼松预防急性排斥反应是安全、有效的,其远期效果有待进一步观察。

Objective To investigate the clinical effectiveness of low-dose sirolimus in living relative kidney transplantation （LRKT） from elder donors, for decreasing nephrotoxicity of CNI, avoiding serum creatinine climbing up, prolonging survival with well-function kidney graft and expanding elder donors as living relative kidney donor source. Methods In all cases subject to LRKT, 19 donors were over 55 years old while recipients were younger than 30. The 19 recipients were ran-domly divided into two groups： Experimental group （n = 9） in which Sirolimus-based imrnunosuppressive protocol （combined with CsA or not） was administered after renal transplantation, and control group （n = 10） in which conventional protocol （consisting of CNI, MMF and steroid） was used. The average of serum creatinine and the incidence of creatinine climbing up, acute rejection and chronic allograft nephropathy （CAN） were measured. The differences between the two groups were analyzed statistically. Results The incidence of biopsy-confirmed acute rejection was similar between the two groups （experimental group vs control group, 11.1 % vs. 10 %, P〉0. 05）. But the rate of CAN was significantly lower in the experimental group than in the control group （ 1 vs 3 cases, P〈0. 05）.After transplantation, mean serum creatinine in the two groups in three phases were contrasted, respectively： （1） 1 year： 70 ± 16 μmol/L vs 73 ± 21 μmol/L （experimental group vs control group）, P 〈0. 05 ; （2） 2 year： 101 ± 19 μmol/L vs 74 ± 27 μmol/L （experimental group vs control group）, P〈 0. 05; （3） 3 year： 126 ± 36 μmol/L vs 87 ± 29μmol/L （experimental group vs control group）, P〈 0. 05. Creatinine climbing up in elder donors was the main reason for second kidney transplantation. By using low-dose sirolimus-based immunosuppressive protocol, there was no difference in the frequency of acute rejection between the two groups. In the experimental group, the rate of CAN and mean serum creatinine after transplantation were decreased significantly. Conclusions Treatment of the low-dose Sirolimus for the recipients with elder donors in LRKT did not increase the risk of acute rejection but protect the graft. This protocol also could prevent the CAN, avoid the renal insufficiency and reduce the rate of second kidney transplantation. It is also positive for expanding the age criteria of donors in LRKT.