慢性肾脏病（CKD）是一种常见、复杂和异质性疾病，对老年人口产生影响。在真实世界环境中确定从中年到老年的疾病进展轨迹，使我们能更好地了解CKD的进展情况、风险人群中进展模式的异质性以及与其他临床情况（如癌症）的相互作用。本研究利用电子健康记录（EHR）描绘Wake Forest Baptist Medical Center（WFBMC）患者人群的CKD进展轨迹。我们建立了一个EHR队列（n = 79,434），通过508,732个临床接触中的18个基本临床指标确定患者的健康状况。我们开发了DisEase PrOgression Trajectory (DEPOT)方法来建立CKD进展轨迹，并个性化临床决策支持。DEPOT是一种有证据支持的基于图形的临床信息学方法，通过系统地使用图形人工智能（图形AI）模型进行表征学习和轨迹重构的图形嵌入来解决纵向EHR数据中的独特挑战。此外，DEPOT还包括一个预测模型，可将新患者分配到进展轨迹上。我们在WFUBMC队列中成功建立了基于EHR的CKD进展轨迹。我们用肾功能、年龄和其他指标（包括癌症）对轨迹进行了注释。该CKD进展轨迹图显示了与不同临床情况相关的多样化肾衰竭途径。具体而言，我们已确定了一个高风险轨迹和两个低风险轨迹。从低风险轨迹转向高风险轨迹与肾功能迅速下降有关。在这个轨迹图上，高风险患者在皮肤和GU癌症方面富集，与低风险患者不同，这表明了根本不同的疾病进展机制。总的来说，CKD进展轨迹图揭示了2型糖尿病中新颖多样的肾衰竭途径，并突出了与癌症表型相关的疾病进展模式。

Chronic kidney disease (CKD) is a common, complex, and heterogeneous disease impacting aging populations. Determining the landscape of disease progression trajectories from midlife to senior age in a real-world context allows us to better understand the progression of CKD, the heterogeneity of progression patterns among the risk population, and the interactions with other clinical conditions like cancers. In this study, we use electronic health records (EHRs) to outline the CKD progression trajectory roadmap for the Wake Forest Baptist Medical Center (WFBMC) patient population. We establish an EHR cohort (n = 79,434) with patients' health status identified by 18 Essential Clinical Indices across 508,732 clinical encounters. We develop the DisEase PrOgression Trajectory (DEPOT) approach to model CKD progression trajectories and individualize clinical decision support. The DEPOT is an evidence-driven, graph-based clinical informatics approach that addresses the unique challenges in longitudinal EHR data by systematically using the graph artificial intelligence (graph-AI) model for representation learning and reverse graph embedding for trajectory reconstruction. Moreover, DEPOT includes a prediction model to assign new patients along the progression trajectory. We successfully establish the EHR-based CKD progression trajectories with DEPOT in the WFUBMC cohort. We annotate the trajectories with clinical features, including kidney function, age, and other indices, including cancer. This CKD progression trajectory roadmap reveals diverse kidney failure pathways associated with different clinical conditions. Specifically, we have identified one high-risk trajectory and two low-risk trajectories. Switching pathways from low-risk trajectories to the high-risk one is associated with accelerated decline in kidney function. On this roadmap, high-risk patients are enriched in the skin and GU cancers, which differs from low-risk patients, suggesting fundamentally different disease progression mechanisms. Overall, the CKD progression trajectory roadmap reveals novel diverse renal failure pathways in type 2 diabetes mellitus and highlights disease progression patterns associated with cancer phenotypes.