Calguneri Meral, Ozbalkan Zeynep, Ozturk M Akif, Apras Sule, Ertenli A Ihsan, Kiraz Sedat
Department of Internal Medicine, Section of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey.
Clin Rheumatol. 2006 Nov;25(6):782-8. doi: 10.1007/s10067-006-0217-2. Epub 2006 Mar 18.
The objective of this study is to evaluate the efficacy, toxicity, and long-term outcome of low-dose IV cyclophosphamid therapy with repeated frequent intervals in combination with oral and IV methylprednisolone in patients with SLE nephritis. In this study, 113 patients diagnosed as having SLE and glomerulonephritis were assessed in between 1993 and 2002, with a median follow-up of 44.1+/-41.2 months. The patients were treated with 500 mg IV cyclophosphamide and 1 g IV methylprednisolone together with 60 mg/alternate-day oral methylprednisolone in a given schedule. The clinical and laboratory data were evaluated. There were significant improvements in the clinical and the laboratory parameters. Six patients died shortly after being hospitalized due to the disease activity itself. Eight patients were excluded from the study because of low compliance. The renal functions of the patients remained stable throughout the therapy; only 16/99 patients needed one or two additional pulses. Temporary leukopenia developed in 18/99 patients and diminished with the suspension or prolongation of the IV cyclophosphamide administration. Gastrointestinal side effects, which needed extra medication, developed in 20 patients. Hematuria was observed in 6/99 patients. Menstrual abnormalities were seen in 7/99 patients. No serious infections due to immunosuppression were observed with the given regimen. Hypertension was observed in 13 patients (minimum of 140/90 mmHg, maximum of 190/110 mmHg) and controlled with angiotensine-converting enzyme inhibitors. Mild central obesity was observed in 15 of the patients. Leimyosarcoma was observed in one patient who died during the follow-up period. Therapy starting with the weekly low-dose IV cyclophosphamide to induce remission together with IV and oral steroids, followed by prolonged intervals with the same doses for 2 years, appears to be useful in preserving renal function without major side effects in patients with lupus nephritis, in comparison to other studies.
本研究的目的是评估在系统性红斑狼疮肾炎患者中,低剂量静脉注射环磷酰胺并频繁重复给药,联合口服和静脉注射甲泼尼龙的疗效、毒性及长期预后。在本研究中,1993年至2002年间对113例诊断为系统性红斑狼疮和肾小球肾炎的患者进行了评估,中位随访时间为44.1±41.2个月。按照既定方案,患者接受500mg静脉注射环磷酰胺、1g静脉注射甲泼尼龙以及60mg隔日口服甲泼尼龙治疗。对临床和实验室数据进行了评估。临床和实验室参数有显著改善。6例患者因疾病活动本身在住院后不久死亡。8例患者因依从性差被排除在研究之外。患者的肾功能在整个治疗过程中保持稳定;仅16/99例患者需要额外进行一或两次冲击治疗。18/99例患者出现暂时性白细胞减少,在暂停或延长静脉注射环磷酰胺给药后减轻。20例患者出现需要额外用药的胃肠道副作用。6/99例患者观察到血尿。7/99例患者出现月经异常。按照给定方案未观察到因免疫抑制导致的严重感染。13例患者出现高血压(最低140/90mmHg,最高190/110mmHg),通过血管紧张素转换酶抑制剂得以控制。15例患者观察到轻度中心性肥胖。1例患者在随访期间死亡,尸检发现平滑肌肉瘤。与其他研究相比,对于狼疮性肾炎患者,起始采用每周低剂量静脉注射环磷酰胺联合静脉和口服类固醇诱导缓解,随后以相同剂量延长给药间隔2年,似乎有助于保护肾功能且无重大副作用。