Tanaka H, Suzuki K, Nakahata T, Tsugawa K, Ito E, Waga S
Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Japan.
Clin Nephrol. 2003 Dec;60(6):390-4. doi: 10.5414/cnp60390.
Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. To relieve disease flare of lupus nephritis, a prospective pilot study of oral MZR pulse therapy (a phase II trial) is conducted as an alternative therapy to dose up of corticosteroids.
Six Japanese patients with biopsy-proven lupus nephritis who experienced disease flare were prospectively evaluated. MZR at a dose of 5 - 10 mg/kg per day (up to 500 mg) in 1 or 2 divided daily doses was orally administered twice a week for 3 months. At the time of disease flare, 4 patients had refused to take dose up of corticosteroids, and the other 2 had complained of opportunistic infection.
At presentation, urine protein excretion, serum hemolytic complement activity (CH50) and serum anti-dsDNA antibody were 1.9 +/- 0.6 g/day, 15.7 +/- 5.8 U/ml (normal 23 - 46 U/ml) and 164.8 +/- 184.0 IU/ml (normal < 12.0 IU/ml), respectively. Urine protein excretion and serum anti-dsDNA antibody decreased significantly following MZR oral pulse therapy (0.2 +/- 0.1 g/day and 29.7 +/- 23.4 IU/ml (p < 0.05), respectively), and serum CH50 recovered to normal (35.1 +/- 10.4 U/ml, p < 0.05). Moreover, a significant histologic improvement was observed in a patient who received repeat renal biopsies at pre- and post-treatment. Reported peak serum MZR levels enough to inhibit human mixed-lymphocyte reaction (3.0 - 6.0 microg/ml) were achieved in all patients. No serious adverse effects were observed.
Although we had no control subjects in this series, MZR oral pulse therapy may be of benefit to a proportion of patients with disease flare of lupus nephritis as an alternative therapy to dose up of corticosteroids.
咪唑立宾（MZR）是日本新开发的一种免疫抑制剂。为缓解狼疮性肾炎的疾病复发，开展了一项口服MZR脉冲疗法的前瞻性试点研究（一项II期试验），作为增加皮质类固醇剂量的替代疗法。
对6例经活检证实患有狼疮性肾炎且经历疾病复发的日本患者进行前瞻性评估。MZR剂量为每日5 - 10mg/kg（最大500mg），分1或2次每日剂量，每周口服2次，共3个月。在疾病复发时，4例患者拒绝增加皮质类固醇剂量，另外2例患者出现机会性感染。
就诊时，尿蛋白排泄量、血清溶血补体活性（CH50）和血清抗双链DNA抗体分别为1.9±0.6g/天、15.7±5.8U/ml（正常23 - 46U/ml）和164.8±184.0IU/ml（正常<12.0IU/ml）。MZR口服脉冲治疗后，尿蛋白排泄量和血清抗双链DNA抗体显著降低（分别为0.2±0.1g/天和29.7±23.4IU/ml，p<0.05），血清CH50恢复正常（35.1±10.4U/ml，p<0.05）。此外，一名在治疗前和治疗后接受重复肾活检的患者出现了显著的组织学改善。所有患者均达到了足以抑制人混合淋巴细胞反应的报告峰值血清MZR水平（3.0 - 6.0μg/ml）。未观察到严重不良反应。
尽管本系列研究中没有对照对象，但MZR口服脉冲疗法作为增加皮质类固醇剂量的替代疗法，可能对一部分狼疮性肾炎疾病复发患者有益。
