Supplementary Material for: Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1

Background The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remains uncertain, warranting further research.
Methods A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS+immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups.
Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS+immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-hour proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 ml/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable.
Conclusion Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

背景：对于伴新月体形成率低于25%的免疫球蛋白A肾病（immunoglobulin A nephropathy, IgAN）C1型病变患者，在糖皮质激素（corticosteroid, CS）治疗基础上加用免疫抑制治疗的肾脏保护获益仍不明确，有待进一步研究。
方法：本研究为回顾性研究，纳入2017年5月1日至2020年5月1日期间在新桥医院经肾活检确诊为C1型新月体病变的IgAN患者。将患者分为糖皮质激素单药治疗组与糖皮质激素联合免疫抑制治疗组，所有患者均接受为期24个月的随访评估。采用倾向性评分分析以1:1比例匹配接受糖皮质激素单药与糖皮质激素联合免疫抑制药物治疗的患者。主要结局指标包括估算肾小球滤过率（estimated glomerular filtration rate, eGFR）、尿白蛋白肌酐比（urine albumin-to-creatinine ratio, UACR）的变化情况。本研究开展亚组分析以评估不同人群的治疗获益，复合终点结局包括eGFR下降30%、需透析或肾移植的终末期肾病（end-stage kidney disease, ESKD）以及肾病相关死亡，同时比较两组患者的不良事件发生情况。
结果：本研究共纳入296例C1型病变IgAN患者进行分析。基线特征显示，糖皮质激素联合免疫抑制治疗组患者的基线肾功能更差、UACR水平更高。倾向性评分分析有效平衡了两组患者的基线临床特征，包括年龄、血清肌酐、基线eGFR、UACR以及24小时尿蛋白定量。随访期间，两组患者的eGFR均呈持续改善趋势，UACR均显著降低，尤以6个月时最为明显。但在匹配前后的整个随访周期内，两组患者的eGFR改善速率与UACR降低速率均无显著差异。亚组分析显示，两组患者的eGFR均有所改善，其中基线eGFR低于90 ml/min/1.73 m²的患者获益尤为显著；反之，对于C1型病变且细胞性新月体占比超过50%的IgAN患者，接受糖皮质激素联合免疫抑制治疗后肾功能显著改善，尿蛋白肌酐比亦明显下降。两组患者的复合终点结局无显著差异，不良事件发生率亦相当。
结论：本研究结果表明，与糖皮质激素单药治疗相比，在C1型病变IgAN患者的糖皮质激素单药治疗基础上加用免疫抑制治疗，并未带来显著的治疗获益，但部分特定人群似乎可从该联合治疗方案中获得轻度益处。