Touchard G, Hauet T, Cogny Van Weydevelt F, Hurault de Ligny B, Peyronnet P, Lebranchu Y, Toupance O, N'Doye P, Busson M
Department of Nephrology, University Hospitals of Poitiers, France.
Nephrol Dial Transplant. 1997 Sep;12(9):1956-60. doi: 10.1093/ndt/12.9.1956.
There is considerable debate about whether maintenance cyclosporin (CsA) monotherapy is advisable or not in renal transplantation.
Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. Initial immunosuppression was sequential: antilymphocyte or antithymocyte globulins (10-14 days), prednisone and azathioprine were combined and CsA was introduced (6-8 mg/kg/day) when the antilymphocyte or antithymocyte globulins were discontinued. When the graft function was stable and the peak of preformed lymphocytotoxic antibodies was < or = 25% and/or the number of rejection episodes was < or = 1, the steroid therapy was stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies > 25% and more than one rejection episode were excluded. Cyclosporin doses were adapted for whole-blood trough levels between 100 and 200 ng/ml (monoclonal antibody radioimmunoassay or high-performance liquid chromatography). Cyclosporin monotherapy was attempted in 234 of the 463 patients.
At the end of the investigation in January 1993 (follow-up time > 36 months, mean 60.5 +/- 4.5 months), 135 patients were receiving CsA without steroids or azathioprine. The 99 CsA monotherapy failures were due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four with poor compliance. Renal function was stable in patients with successful CsA monotherapy: mean creatininaemia was 124 +/- 10 mumol/l at the time of CsA monotherapy inclusion and 129 +/- 10 mumol/l at the end of follow-up (mean time of CsA monotherapy 52 +/- 6 months). The parameters for predicting monotherapy success were age (43.2 versus 37.8. P = 0.0014), timing of trial inclusion > or = 6 months post-transplant (7.9 +/- 3 versus 5.3 +/- 3.1 months, P = 0.04), and excellent and stable renal function at the time of inclusion (124 +/- 10 versus 145 +/- 32 mumol/l, P < 0.001).
Maintenance CsA monotherapy was effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patient and graft survival were respectively 90 and 73% at 6 years. We propose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time post-transplantation > 6 months, and stable creatininaemia levels.
对于肾移植中维持性环孢素（CsA）单一疗法是否可取存在相当大的争议。
1984年8月至1989年12月期间，463例成年患者接受了首次尸体肾移植。初始免疫抑制采用序贯疗法：抗淋巴细胞或抗胸腺细胞球蛋白（10 - 14天），联合泼尼松和硫唑嘌呤，当停用抗淋巴细胞或抗胸腺细胞球蛋白时引入CsA（6 - 8mg/kg/天）。当移植肾功能稳定且预先形成的淋巴细胞毒性抗体峰值≤25%和/或排斥反应次数≤1次时，移植后1.5 - 3个月内停用类固醇疗法，3 - 12个月内停用硫唑嘌呤。抗HLA抗体>25%且有不止一次排斥反应的患者被排除。根据全血谷浓度在100至200ng/ml之间（单克隆抗体放射免疫测定或高效液相色谱法）调整CsA剂量。463例患者中的234例尝试采用CsA单一疗法。
在1993年1月调查结束时（随访时间>36个月，平均60.5±4.5个月），135例患者在未使用类固醇或硫唑嘌呤的情况下接受CsA治疗。99例CsA单一疗法失败病例中，48例是由于排斥反应，26例是由于CsA肾毒性，25例是由于其他原因，包括5例死亡和4例依从性差。CsA单一疗法成功的患者肾功能稳定：纳入CsA单一疗法时平均肌酐血症为124±10μmol/l，随访结束时为129±10μmol/l（CsA单一疗法平均时间52±6个月）。预测单一疗法成功的参数为年龄（43.2对37.8，P = 0.0014）、移植后≥6个月纳入试验的时间（7.9±3对5.3±3.1个月，P = 0.04）以及纳入时肾功能良好且稳定（124±10对145±32μmol/l，P<0.001）。
维持性CsA单一疗法在58%的低免疫风险首次移植患者中有效，可能不会危及我们首次移植的总体结果：6年时患者和移植肾存活率分别为90%和73%。我们建议对选定的免疫风险低、移植后随访时间>6个月且肌酐血症水平稳定的依从性受者采用该策略，以避免糖皮质激素和硫唑嘌呤的长期并发症。
