Rasche F M, Keller F, Rasche W G, Schiekofer S, Kahn T, Fahnert J
Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Nephrology, Section of Nephrology, University Leipzig, Leipzig, Germany.
Department of Internal Medicine I, Division of Nephrology, University Hospital of Ulm, Ulm, Germany.
Clin Exp Immunol. 2016 Feb;183(2):307-16. doi: 10.1111/cei.12719. Epub 2015 Nov 26.
In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long-term follow-up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP-MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy-proven IgAN and treated with CyP. Thirty-one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow-up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from -0·4 ml/min to -0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2-17·8), with CyP-MPA 10·7 years (range = 8·3-13·1), with IVIg 4·7 years (range = 2·6-6·6), and in untreated patients 1·2 years (range = 0·8-1·6; log-rank test P < 0·01). In patients with progressive IgAN, our long-term follow-up observation indicates that sequential CyP-MPA therapy maintains renal survival significantly.
在进行性免疫球蛋白A（IgA）肾病（IgAN）中，环磷酰胺脉冲疗法（CyP）、大剂量静脉注射免疫球蛋白（IVIg）和霉酚酸（MPA）已被用于阻止肾功能的进行性丧失，但在初始治疗结束后疾病仍可能进展。在此，我们报告了以MPA作为CyP（CyP-MPA）后维持治疗的进行性IgAN患者的长期随访情况。在中位观察时间6.2年里，我们分析了47例经活检证实为IgAN并接受CyP治疗的患者肾功能丧失的斜率。31例病情进一步进展的患者接受了MPA维持治疗，中位时间为5.2年。将随访结果与对症治疗组和IVIg组作为历史匹配对照组进行比较。CyP治疗期间，肾功能的中位丧失率从每月0.9 ml/min显著降低至0.1 ml/min（P<0.05），而复发患者接受MPA治疗至研究结束时，肾功能丧失率从每月-0.4 ml/min降至-0.1 ml/min（P<0.05）。蛋白尿在CyP治疗后从1.6 g/l显著降至1.0 g/l，在MPA治疗期间降至0.6 g/l（Friedman检验，P=0.001）。接受CyP治疗患者的中位肾脏生存时间为10.5年（范围=3.2-17.8年），接受CyP-MPA治疗患者为10.7年（范围=8.3-13.1年），接受IVIg治疗患者为4.7年（范围=2.6-6.6年），未治疗患者为1.2年（范围=0.8-1.6年；对数秩检验，P<0.01）。在进行性IgAN患者中，我们的长期随访观察表明，序贯CyP-MPA疗法可显著维持肾脏生存。
