Ioannidis J P, Boki K A, Katsorida M E, Drosos A A, Skopouli F N, Boletis J N, Moutsopoulos H M
Division of Clinical Care Research, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
Kidney Int. 2000 Jan;57(1):258-64. doi: 10.1046/j.1523-1755.2000.00832.x.
Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide.
Long-term intravenous cyclophosphamide (IVC) in combination with corticosteroids is standard therapy for proliferative lupus nephritis, but it has limitations. There are few data on long-term remission rates, predictors of relapse, and the ability to achieve a second remission with currently recommended IVC regimens.
A cohort of 85 patients with proliferative lupus glomerulonephritis (focal N = 33, diffuse N = 52) treated with IVC was assembled in three institutions. Timing and predictors of remission, relapse, and re-remission were evaluated with Kaplan-Meier analyses and Cox models.
The median time to remission was 10 months, whereas an estimated 22% of patients had not remitted after 2 years. The median time to relapse among 63 patients who had achieved remission was 79 months. In multivariate models, adverse predictors of remission were a delay in the initiation of therapy from the time nephritis was clinically diagnosed [hazard ratio (HR) 0.58, P = 0. 063] and a higher amount of proteinuria (HR 0.86 per 1 g/24 hours, P = 0.014). Predictors of earlier relapse for patients entering remission included a longer time to remission (HR 1.029 per month, P = 0.025), a history of central nervous system involvement (HR 8.41, P = 0.002), and World Health Organization histology (P = 0.01). Among the 23 patients who relapsed during follow-up, the median time to re-remission was 32 months, and with three exceptions, all patients took substantially longer time to remit the second time compared with their first remission (P = 0.01). The time to re-remission was longer in patients who had taken longer to remit the first time (HR 0.979 per month, P = 0.16), in patients who had relapsed earlier after the first remission (HR 1.071 per month, P = 0.002), and in those with evidence of chronicity in the original kidney biopsy (P = 0.015).
Prolonged courses with a cumulative risk of toxicity are needed to achieve remission in many first-treated patients and in most patients treated for a second time. The optimal management of patients with identified adverse predictors of response needs further study.
环磷酰胺治疗增殖性狼疮性肾炎的缓解、复发及再次缓解情况
长期静脉注射环磷酰胺（IVC）联合糖皮质激素是增殖性狼疮性肾炎的标准治疗方法，但存在局限性。关于长期缓解率、复发预测因素以及目前推荐的IVC方案实现二次缓解能力的数据较少。
在三个机构收集了85例接受IVC治疗的增殖性狼疮性肾小球肾炎患者队列（局灶性33例，弥漫性52例）。采用Kaplan-Meier分析和Cox模型评估缓解、复发及再次缓解的时间和预测因素。
缓解的中位时间为10个月，而估计22%的患者在2年后仍未缓解。63例缓解患者的复发中位时间为79个月。在多变量模型中，缓解的不良预测因素是从临床诊断肾炎开始治疗的延迟（风险比[HR]0.58，P = 0.063）和蛋白尿水平较高（每1g/24小时HR 0.86，P = 0.014）。进入缓解期的患者早期复发的预测因素包括缓解时间较长（每月HR 1.029，P = 0.025）、中枢神经系统受累史（HR 8.41，P = 0.002）和世界卫生组织组织学分类（P = 0.01）。在随访期间复发的23例患者中，再次缓解的中位时间为32个月，除3例例外，所有患者第二次缓解所需时间比第一次缓解长得多（P = 0.01）。首次缓解所需时间较长的患者再次缓解时间较长（每月HR 0.979，P = 0.16），首次缓解后较早复发的患者再次缓解时间较长（每月HR 1.071，P = 0.002），以及原肾活检有慢性病变证据的患者再次缓解时间较长（P = 0.015）。
许多初治患者和大多数二次治疗患者需要延长疗程并累积毒性风险才能实现缓解。对已确定有不良反应预测因素的患者的最佳管理需要进一步研究。
