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. 2025 Feb 20;45(2):379-386.
doi: 10.12122/j.issn.1673-4254.2025.02.19.

[High serum cystatin C is an independent risk factor for poor renal prognosis in IgA nephropathy]

[Article in Chinese]
Tianwei Tang  1 , Luan Li  2 , Yuanhan Chen  2 , Li Zhang  2 , Lixia Xu  2 , Zhilian Li  2 , Zhonglin Feng  2 , Huilin Zhang  3 , Ruifang Hua  3 , Zhiming Ye  2 , Xinling Liang  2 , Ruizhao Li  1
Affiliations

[High serum cystatin C is an independent risk factor for poor renal prognosis in IgA nephropathy]

[Article in Chinese]
Tianwei Tang et al. Nan Fang Yi Ke Da Xue Xue Bao. .

Abstract
in English, Chinese

Objectives: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients.

Methods: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC).

Results: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ2=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945).

Conclusions: Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.

目的: 探讨血清胱抑素C（CysC）水平评估IgA肾病（IgAN）患者肾脏预后的价值。方法: 回顾性收集2014年1月~2018年12月在广东省人民医院通过肾穿刺活检诊断为IgAN患者的临床资料。根据基线血清CysC值将患者分为高血清CysC组（CysC>1.03 mg/L）和正常血清CysC组（CysC≤1.03 mg/L）。估算肾小球滤过率（eGFR）下降≥50%，和/或进入终末期肾病（ESRD）作为肾脏不良预后的随访复合终点事件。采用lasso回归和多因素Cox回归筛选独立危险因素，并基于这些独立危险因素构建多因素Cox回归预测模型。采用Kaplan⁃Meier生存分析比较两组之间的肾脏生存率差异。平滑曲线拟合及阈值效应探究血清CysC水平与结局之间的关系。通过Bootstrap法内部验证预测模型并使用一致性指数、校正曲线、受试者工作特征（ROC）曲线及其曲线下面积（AUC）对模型预测效能进行评价，并通过列线图可视化。结果: 本研究共纳入356例IgAN患者，平均随访时间为（4.65±0.93）年，74例发生肾脏不良预后的复合终点事件。高血清CysC被筛选为IgAN肾脏不良预后的独立危险因素（HR=2.142，95% CI：1.222~3.755），且血清CysC水平高的患者肾脏生存率较低（Log-rank检验χ2=47.970，P<0.001）。阈值效应分析显示，当患者血清CysC≤2.12 mg/L时，血清CysC水平越高，肾脏不良预后风险越大（β=3.487，95% CI：2.561~4.413，P<0.001）；当患者的血清CysC>2.12 mg/L时，肾脏不良预后的发生风险仍有上升但差异无统计学意义（β=0.676，95% CI：-0.642~1.995，P=0.315）。基于血清 CysC及其他3个独立危险因素构建的多因素Cox回归预测模型经内部验证表现良好，其一致性指数为0.873（95% CI：0.839~0.907），AUC为0.909（95% CI：0.873~0.945）。结论: 血清CysC水平与IgAN患者肾脏预后相关，高血清CysC是IgA肾病不良预后的独立危险因素。.

Keywords: IgA nephropathy; prognosis; serum cystatin C.

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Figures

图1
图1
Lasso回归模型筛选变量 Fig.1 Variable selection by Lasso regression model. A: Log Lambda versus partial likelihood deviance. B: Log Lambda versus coefficients.
图2
图2
Kaplan⁃Meier生存曲线分析血清CysC对IgAN患者5年肾脏生存率的影响 Fig.2 Kaplan-Meier survival curves for analyzing the effect of serum CysC on 5-year renal survival rate of IgAN patients.
图3
图3
广义加性模型描述血清CysC水平与IgAN肾脏不良预后之间的关系 Fig.3 Generalized additive models demonstrate the relationship between serum CysC level and poor renal prognosis of IgAN.
图4
图4
IgAN患者预后的列线图模型 Fig.4 Nomogram prediction model of the prognosis of IgAN patients.
图5
图5
列线图模型的校准曲线 Fig.5 Calibration curve of nomogram prediction model.
图6
图6
列线图模型的ROC曲线 Fig.6 ROC curve of nomogram prediction model.
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