Risk of onset of chronic kidney disease in type 2 diabetes mellitus (ROCK-DM): Development and validation of a 4-variable prediction model.

Jie Ming Nigel Fong, Serena Low, Yang Xu, Pek Siang Edmund Teo, Gek Hsiang Lim, Huili Zheng, Keven Ang, Ngiap Chuan Tan, Cheng Boon Poh, Hui Boon Tay, Allen Yan Lun Liu, Choong Meng Chan, Chieh Suai Tan, Su Chi Lim, Yong Mong Bee, Jia Liang Kwek
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Abstract

Aims: The aim of this study was to develop and validate a prediction model for incident chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM), defined as eGFR < 60 ml/min/1.73m2 and/or urine albumin:creatinine ratio (UACR) > 3 mg/mmol in ≥ 2 consecutive readings ≥ 3 months apart.

Methods: Model derivation was performed in the SingHealth Diabetes Registry, including patients aged ≥ 21 years diagnosed with T2DM without pre-existing CKD. External validation was performed in a single-center prospective observational cohort. Cox Proportional Hazard model was created to evaluate predictors associated with time-to-onset of incident CKD. Increasingly parsimonious models were assessed for discrimination and calibration. Models underwent external validation, benchmarking against existing models, and decision curve analysis.

Results: 25,142 (59 %) of 42,552 patients in the derivation cohort developed CKD over a median 4.0 years (IQR 2.1-7.7) follow up. An 18-variable model, 12-variable model, and 4-variable model (including age, duration of T2DM, eGFR, and previous non-persistent albuminuria) was developed. The 4-variable model had a C-statistic of 0.78 and good calibration on plots of observed-versus-predicted risk. The 12-variable and 18-variable models performed similarly. In the external validation cohort of 2249 patients, of whom 1035 (46 %) developed incident CKD, the 4-variable model had a C-statistic of 0.87. All models had better discrimination than existing benchmarks. Decision curve analysis of the 4-variable model showed positive net benefit for any threshold probability above 16 % for 2-year and 28 % for 5-year CKD risk.

Conclusion: The 4-variable model for prediction of incident CKD in T2DM demonstrates good performance, predicts both eGFR and albuminuria endpoints, and is simple-to-use. This may guide personalized care, resource allocation and population health.

目的:本研究旨在开发和验证 2 型糖尿病(T2DM)患者慢性肾脏病(CKD)的预测模型:模型推导在新加坡保健集团糖尿病登记处进行,包括年龄≥ 21 岁、确诊为 T2DM 但无原有 CKD 的患者。外部验证在单中心前瞻性观察队列中进行。建立了 Cox 比例危险模型,以评估与 CKD 发病时间相关的预测因素。对越来越简化的模型进行了判别和校准评估。结果:在中位随访 4.0 年(IQR 2.1-7.7)的 42,552 名衍生队列患者中,有 25,142 人(59%)发展为 CKD。建立了一个 18 变量模型、12 变量模型和 4 变量模型(包括年龄、T2DM 持续时间、eGFR 和既往非持续性白蛋白尿)。4 变量模型的 C 统计量为 0.78,在观察风险与预测风险图上校准良好。12 变量模型和 18 变量模型的表现类似。在由 2249 名患者组成的外部验证队列中,有 1035 名患者(46%)发生了慢性肾脏病,4 变量模型的 C 统计量为 0.87。所有模型的区分度均优于现有基准。4 变量模型的决策曲线分析表明,任何阈值概率超过 16% 的 2 年期 CKD 风险和 28% 的 5 年期 CKD 风险都会带来正的净收益:预测 T2DM 患者发生 CKD 的 4 变量模型性能良好,可预测 eGFR 和白蛋白尿终点,而且简单易用。这可以为个性化护理、资源分配和人口健康提供指导。
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