基于机器学习的老年原发性膜性肾病预后预测模型

Prognostic Prediction Model for Primary Membranous Nephropathy in the Elderly Based on Machine Learning

  • 摘要: 目的 老年原发性膜性肾病(primary membranous nephropathy,PMN)预后异质性显著、免疫治疗耐受性差,目前缺乏针对该人群的早期预后预测工具。本研究旨在构建适用于老年PMN的预后预测模型。方法 本研究回顾性纳入经肾活检确诊PMN的老年患者,主要终点事件为复合肾脏不良结局,包括:终末期肾脏病、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)下降50%或全因死亡。所有患者按7∶ 3比例随机划分为训练集和验证集。采用最小绝对收缩与选择算子(least absolute shrinkage and selection operator,LASSO)回归联合随机生存森林筛选重要特征,并基于惩罚Cox回归构建预测模型。通过C指数(C-index)、时间依赖受试者工作特征曲线下面积(area under the receiveroperating characteristic curve,AUROC)、校准曲线和决策曲线分析评估模型性能,并采用SurvSHAP (t)方法对模型进行可解释性分析。结果 本研究共纳入309例老年PMN患者,中位年龄为65.00(62.00,68.00)岁,其中男性占61.2%(189/309)。在中位随访47.00(25.00,89.00)个月的随访期内,38.2%(118/309)的患者发生终点事件。最终模型纳入eGFR、总蛋白、肾小球囊粘连、尿糖、肾小球节段硬化比例、纤维蛋白原、尿素、年龄、活化部分凝血活酶时间9个关键特征。在验证集中,模型表现出良好的区分度,C指数为0.731(95% CI: 0.652~0.797)。模型在预测3年、5年及10年不良结局的时间依赖性AUROC分别为0.758(95% CI: 0.614~0.901)、0.781(95% CI: 0.646~0.916)和0.866(95% CI: 0.740~0.993)。校准曲线显示预测概率与实际发生率高度吻合,决策曲线分析证实了模型在临床决策中的净获益。结论 该预测模型在验证集中可有效预测老年PMN患者的不良结局风险,有望为老年PMN的个体化风险分层及治疗决策提供科学依据。

     

    Abstract: Objective Elderly patients with primary membranous nephropathy (PMN) exhibit significant prognostic heterogeneity and poor tolerance to immunotherapy. However, there is a lack of early prognostic prediction tools specifically for this population. This study aimed to develop a prognostic prediction model applicable to elderly PMN patients. Methods This study retrospectively included elderly patients with PMN confirmed by renal biopsy. The primary endpoint was a composite renal adverse outcome including end-stage renal disease (ESRD), a 50% decline in estimated glomerular filtration rate (eGFR), or all-cause death. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Key prognostic features were identified using least absolute shrinkage and selection operator (LASSO) regression combined with random survival forest, and a predictive model was constructed based on penalized Cox regression. Model performance was evaluated using the concordance index (C-index), time-dependent area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curve analysis. The SurvSHAP(t) method was employed for interpretability analysis of the model. Results A total of 309 elderly patients with PMN were included in this study, with a median age of 65.00 years (IQR, 62.00–68.00) and a male predominance (61.2%, 189/309). During a median follow-up of 47.00 months (IQR, 25.00-89.00), 38.2% (118/309) reached the endpoint event. The final model included nine key features, including eGFR, total protein, glomerular capsular adhesion, glucosuria, segmental glomerulosclerosis proportion, fibrinogen, urea, age, and activated partial thromboplastin time (APTT). In the validation set, the model demonstrated good discrimination, with a C-index of 0.731 (95% CI: 0.652-0.797). The time-dependent AUROCs for predicting adverse outcomes at 3, 5, and 10 years were 0.758 (95% CI: 0.614–0.901), 0.781 (95% CI: 0.646–0.916), and 0.866 (95% CI: 0.740–0.993), respectively. Calibration curves demonstrated a high degree of concordance between predicted probabilities and actual event rates. Decision curve analysis confirmed the net clinical benefit of the model.Conclusions This prognostic model effectively predicts the risk of adverse outcomes in elderly patients with PMN in the internal validation cohort, offering a potential scientific basis for individualized risk stratification and treatment decision-making in this population.

     

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