BACKGROUND The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial. METHODS This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0 g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD. RESULTS All patients were followed for a medial of 33.2 months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73 m2 per year. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups. CONCLUSION Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.

中文翻译：

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治疗 3 期或 4 期慢性肾病的 IgA 肾病：低剂量皮质类固醇联合口服环磷酰胺。

背景 对 IgA 肾病肾功能不全和严重蛋白尿患者使用免疫抑制治疗是有争议的。方法 这是一项单中心回顾性研究。我们回顾了 132 名接受不受控制的支持治疗 (n = 41)、皮质类固醇 (CS) (n = 22) 或低剂量 CS 的连续 3 或 4 期慢性肾病和蛋白尿 ≥ 1.0 g/d 的 IgA 肾病 (IgAN) 患者2008 年 1 月至 2016 年 12 月期间与口服环磷酰胺 (CTX) (n = 69) 联合使用。联合终点定义为 eGFR 或 ESRD 降低 ≥ 50%。结果 所有患者均进行了为期 33.2 个月的中期随访，67 名 (50.8%) 患者经历了综合终点。肾功能下降的速度为 - 4.5 (- 12.6, - 0.1) ml/min/1.73 m2 每年。在多变量 Cox 回归分析中，免疫抑制治疗（HR = 0.349，95% CI 0.194-0.629，P < 0.001）在调整年龄、性别、MAP、蛋白尿、eGFR、系膜细胞过多评分> 0.5 (M1)、毛细血管内细胞过多后与联合事件风险降低相关存在 (E1)、存在节段性肾小球硬化 (S1)、肾小管萎缩/间质纤维化 > 25% (T1-2)、存在新月体 (C1-2) 和 RAAS 阻滞剂。免疫抑制治疗也作为分类变量进行分析，多变量 Cox 分析表明 CS 并没有降低联合事件的风险，而 CS + CTX 显着降低了联合事件的风险。在匹配的队列中，CS + CTX 组的 TP-A 降低显着更低 [1.2 (0.6, 2.3) g/d 对比 1.8 (1.2, 2.5), P = 0.023] 和更好的肾脏存活率 (39.4%)第 66.7% 节，P = 0。026) 比不受控制的支持治疗组。在三个研究组中，感染所需的住院次数相似。其他不良事件在三组之间没有显着差异。结论 对于肾功能下降的 IgAN 患者，低剂量 CS 联合口服 CTX 治疗可能比不受控制的支持治疗更有效。研究结果还需要随机对照研究进一步证实。