Barbour Sean J, Ronco Pierre, Praga Manuel, Fervenza Fernando C, Induruwage Dilshani, Zhu Bingyue, Debiec Hanna, Fernández-Juárez Gema, Caravaca-Fontán Fernando, Cattran Daniel C
Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
BC Renal, Vancouver, British Columbia, Canada.
Clin J Am Soc Nephrol. 2025 Apr 14;20(6):854-865. doi: 10.2215/CJN.0000000694.
In phospholipase A2 receptor-membranous nephropathy, clinical variables and antibody levels over 3 or 6 months of treatment were predictors of remission at 1 year. Prediction models at 3 and 6 months had similar performance predicting remission, with the 3-month model allowing for earlier assessment of response. The 3-month and 6-month prediction models could be applied in those treated with supportive therapy, rituximab, calcineurin inhibitors, or cyclophosphamide.
In patients with antiphospholipase A2 receptor antibody–associated membranous nephropathy, there is currently no accepted method to predict an individual's probability of remission after treatment with immunosuppression or supportive therapy using changes in antibody levels and clinical variables during the first 3–6 months of therapy.
Using a cohort of 187 patients from the Glomérulopathie extramembraneuse rituximab, Membranous Nephropathy Trial of Rituximab, and Sequential Treatment with Tacrolimus and Rituximab Versus Alternating Corticosteroids and Cyclophosphamide in primary Membranous Nephropathy clinical trials with antibody levels at baseline ≥14 RU/ml, we derived logistic regression models to predict proteinuria remission at 12 months that can be used at baseline or after 3 or 6 months of treatment. Treatment exposures in the trials included supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide. Predictors in the models included male sex and baseline and changes in serum albumin, proteinuria, and antibody levels, with or without changes in eGFR.
Proteinuria remission at 12 months was achieved in 107 patients. Compared with the model at baseline, the 3-month and 6-month models had better model fit with lower Akaike information criterion (186/158 versus 225) and higher R (52.7%/62.4% versus 25.8%), better discrimination with higher C-statistic (0.87 and 0.91 versus 0.75, < 0.001), and better calibration with lower integrated calibration index (0.89%/2.22% versus 2.51%). The 3-month and 6-month models had no consistent difference in prediction performance, and decision curve analysis demonstrated similar net benefit for treatment decisions based on either model up to a threshold probability of 31%. Prediction performance was similar after internal validation using optimism correction. Prediction performance was maintained within subgroups of different treatment regimens, including supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide.
Either the 3-month or 6-month models can be used in patients with antiphospholipase A2 receptor antibody associated membranous nephropathy after 3 or 6 months of treatment with a variety of immunosuppression or supportive therapy to predict remission status at 12 months.
在磷脂酶A2受体相关性膜性肾病中，治疗3或6个月时的临床变量和抗体水平是1年缓解的预测指标。3个月和6个月时的预测模型在预测缓解方面具有相似的性能，3个月模型可更早评估反应。3个月和6个月预测模型可应用于接受支持治疗、利妥昔单抗、钙调神经磷酸酶抑制剂或环磷酰胺治疗的患者。
在抗磷脂酶A2受体抗体相关膜性肾病患者中，目前尚无公认的方法可利用治疗前3至6个月期间抗体水平和临床变量的变化来预测个体经免疫抑制或支持治疗后缓解的概率。
利用来自“肾小球外膜性疾病利妥昔单抗”、“利妥昔单抗膜性肾病试验”以及“原发性膜性肾病中他克莫司与利妥昔单抗序贯治疗对比交替使用皮质类固醇和环磷酰胺”临床试验的187例患者队列，这些患者基线抗体水平≥14 RU/ml，我们推导了逻辑回归模型以预测12个月时的蛋白尿缓解情况，该模型可在基线时或治疗3或6个月后使用。试验中的治疗暴露包括支持治疗、利妥昔单抗、钙调神经磷酸酶抑制剂和环磷酰胺。模型中的预测指标包括男性性别以及基线和血清白蛋白、蛋白尿、抗体水平的变化，无论估算肾小球滤过率（eGFR）有无变化。
107例患者在12个月时实现蛋白尿缓解。与基线模型相比，3个月和6个月模型具有更好的模型拟合度，Akaike信息准则更低（186/158对225）且R更高（52.7%/62.4%对25.8%），具有更好的区分度，C统计量更高（0.87和0.91对0.75，P<0.001）以及更好的校准度，综合校准指数更低（0.89%/2.22%对2.51%）。3个月和6个月模型在预测性能上无一致差异，决策曲线分析表明，基于任一模型进行治疗决策直至阈值概率为31%时，净效益相似。经乐观校正的内部验证后，预测性能相似。在不同治疗方案的亚组中，包括支持治疗、利妥昔单抗、钙调神经磷酸酶抑制剂和环磷酰胺，预测性能均得以维持。
对于接受各种免疫抑制或支持治疗3或6个月后的抗磷脂酶A2受体抗体相关膜性肾病患者，3个月或6个月模型均可用于预测12个月时的缓解状态。
