原发性膜性肾病患者合并动脉粥样硬化性心血管疾病影响因素分析及列线图预测模型建立

    Analysis of influencing factors for primary membranous nephropathy complicated with atherosclerotic cardiovascular disease and establishment of a nomogram prediction model

    • 摘要: 目的 用机器深度学习法研究原发性膜性肾病(primary membranous nephropathy,PMN)患者动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)的危险因素,并建立列线图模型。方法 回顾性纳入2017年9月1日至2023年5月31日在新疆医科大学第一附属医院做过肾穿刺诊断膜性肾病患者620例。按纳入排除标准,最终424例PMN患者被纳入我们的研究,其中包含219例ASCVD。患者按7∶3的比例被分成训练组(n=297)和验证组(n=127)。使用Mann-Whitney U检验、独立样本t检验及卡方检验进行单因素筛选,并使用LASSO回归进一步优化筛选变量,建立列线图预测模型,通过可视化统计方法对临床模型的有效性进行了评估。结果 ASCVD组与非ASCVD组患者比较,年龄更大56(51,63)岁比35(28,44)岁,男性占比更多154(70.3%)比117(57.1%),吸烟占比更多71(32.4%)比43(21.0%),饮酒占比更多54(24.7%)比32(15.6%),收缩压更高130(120,142)mmHg(1 mmHg=0.133 kPa)比122.0(113.5,135.5)mmHg,舒张压更高80(75,90)mmHg比80.0(70.0,85.5)mmHg,高血压占比更高142(64.8%)比67(32.7%),体力工作者占比更多60(27.4%)比28(13.7%)。此外,淋巴细胞计数、血小板计数、血钠浓度、尿素氮、血肌酐、估算肾小球滤过率、24 h尿蛋白定量、天冬氨酸转氨酶、尿潜血、尿透明管型及病理管型数、C反应蛋白、补体C4、凝血酶原时间、血浆纤维蛋白原、D二聚体、中性粒细胞淋巴细胞比值比较,差异有统计学意义(P<0.05)。采用LASSO回归分析方法,筛选出4个与PMN患者发生ASCVD风险相关的预测变量,得到年龄、高血压、尿素氮、估算肾小球滤过率是PMN患者ASCVD的风险因素。训练组ASCVD发生风险的受试者工作特征(receiver operating characteristic,ROC)曲线的曲线下的面积(area under curve,AUC)为0.924(95%CI:0.895~0.952),验证组ASCVD发生风险的AUC为0.932(95%CI:0.892~0.972)。校准曲线Hosmer-Lemeshow拟合度较好(训练组P=0.827;验证组P=0.389)。决策曲线分析显示当患者的阈值概率为0.01~1时,使用列线图预测模型预测PMN患者发生ASCVD风险均有益。结论 本研究发现年龄、高血压、尿素氮、估算肾小球滤过率是PMN患者并发ASCVD的风险因素,建立了包含该4个风险因素的列线图预测模型,可用于预测PMN患者发生ASCVD的风险。

       

      Abstract: Objective To investigate the risk factors for atherosclerotic cardiovascular disease(ASCVD) in primary membranous nephropathy(PMN) patients by machine deep learning, and to construct a nomogram. Methods This was a retrospective study including 620 patients with membranous nephropathy diagnosed by renal puncture in the First Affiliated Hospital of Xinjiang Medical University from September 1, 2017 to May 31, 2023. Based on inclusion and exclusion criteria. Eligible 424 PMN patients were finally enrolled, involving 219 ASCVD patients. They were assigned into the training (n=297) and validation groups at a 7∶3 ratio. The Mann-Whitney U test and independent-sample t test were used to screen influencing factors for ASCVD in PMN patients. LASSO regression was applied to optimize the screening variables. A nomogram was constructed and validated for its performance through visualized statistical methods. Results Compared with patients in the non-ASCVD group, those in the ASCVD group were significantly older 56(51, 63) years vs 35(28, 44) years, and had significantly higher proportions of males 154(70.3%) vs 117(57.1%), smokers71(32.4%) vs 43(21.0%), and alcohol consumption54(24.7%) vs 32(15.6%). They also had significantly higher systolic blood pressure 130(120, 142) mmHg(1 mmHg=0.133 kPa) vs 122.0(113.5, 135.5) mmHg, higher diastolic blood pressure 80 (75, 90) mmHg vs 80(70, 85.5) mmHg, higher prevalence of hypertension142(64.8%) vs 67 (32.7%), and higher proportion of manual workers60(27.4%) vs 28(13.7%) Additionally, lymphocyte count (LYM), platelet count (PLT), blood sodium concentration (Na), blood urea nitrogen (BUN), blood creatinine (Cr), estimated glomerular filtration rate (eGFR), 24-hour quantitative urine protein, glutamic transaminase, urinary occult blood, number of urinary hyaline and pathological tubular patterns, C-reactive protein (CRP), complement C4, plasma fibrinogen, D-dimer, and centrocyte-lymphocyte ratio were all significantly different between the two groups (P<0.05). Age, hypertension, BUN and eGFR were selected as risk factors for predicting ASCVD of PMN patients through LASSO regression. The area under the ROC curve (AUC) of the nomogram to predict ASCVD was 0.924 (95% CI: 0.895-0.952) in the training group, and 0.932 (95% CI: 0.892-0.972) in the validation group. The calibration curve Hosmer-Leme showed the fit was good (P=0.827 for the training group; P=0.389 for the validation group). DCA showed that the use of nomogram prediction model was more beneficial in predicting ASCVD in PMN when the threshold probability of patients was 0.01 to 1. Conclusion The nomogram prediction model containing four predictor variables (age, hypertension, BUN, eGFR) developed in this study can be used to predict the risk of ASCVD in patients with PMN.

       

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