Włodarczyk Z, Wałaszewski J, Perner F, Vitko S, Ostrowski M, Bachleda P, Kokot F, Klinger M, Szenohradsky P, Studenik P, Navratil P, Asztalos L, Rutkowski B, Nagy K Kalmar, Hickey D
Department of Transplantology, Poznan District Hospital, Poznan, Poland.
Ann Transplant. 2002;7(3):28-31.
This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids.
In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months.
Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S).
Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.
本前瞻性、随机、多中心研究调查了两种基于他克莫司的治疗方案的疗效和安全性，以及停用类固醇的可能性。
总共489例患者被随机分为两组，一组接受他克莫司和霉酚酸酯（n = 243），另一组接受他克莫司和硫唑嘌呤（n = 246），两组均同时使用类固醇。他克莫司初始口服剂量为0.2mg/kg/天，霉酚酸酯剂量为1g/天，硫唑嘌呤剂量为1 - 2mg/天。类固醇从20mg/天逐渐减量至5mg/天。从第3个月起，对于无类固醇抵抗性排斥反应且血清肌酐浓度<160μmol/L的患者停用类固醇。研究持续时间为6个月。
第6个月时患者生存率为他克莫司/霉酚酸酯/类固醇组98.3%，他克莫司/硫唑嘌呤/类固醇组98.4%；6个月时移植物生存率为他克莫司/霉酚酸酯/类固醇组95.0%，他克莫司/硫唑嘌呤/类固醇组93.5%。经活检证实的急性排斥反应6个月发生率在他克莫司/霉酚酸酯/类固醇组为18.9%，而他克莫司/硫唑嘌呤/类固醇组为26.8%，p = 0.038。类固醇抵抗性急性排斥反应6个月发生率在他克莫司/霉酚酸酯/类固醇组为2.1%，他克莫司/硫唑嘌呤/类固醇组为4.9%，p = 无统计学意义。在第3个月末，他克莫司/霉酚酸酯/类固醇组60.5%的患者和他克莫司/硫唑嘌呤/类固醇组48.8%的患者停用了类固醇，p < 0.01。在第4 - 6个月期间，他克莫司/霉酚酸酯组2.7%的患者经活检证实发生急性排斥反应，而他克莫司/硫唑嘌呤组为0.8%。在继续接受类固醇治疗的患者中，第4 - 6个月经活检证实的急性排斥反应发生率在他克莫司/霉酚酸酯/类固醇组为3.5%，他克莫司/硫唑嘌呤/类固醇组为7.1%。研究结束时，无类固醇患者肾功能良好；他克莫司/霉酚酸酯组血清肌酐中位数浓度为119.5μmol/L，他克莫司/硫唑嘌呤组为115.1μmol/L；整个研究组血清肌酐中位数为他克莫司/霉酚酸酯/类固醇组130.5μmol/L，他克莫司/硫唑嘌呤/类固醇组132.8μmol/L。
两种他克莫司治疗方案均有效且安全。他克莫司与霉酚酸酯联合使用可降低排斥反应发生率，并使无类固醇患者比例更高。急性排斥反应总体发生率较低且肾功能良好。
