Scientific Reports · Apr 21, 2026

Uncovering core diseases in temporal trajectories of cardiovascular-kidney-metabolic (CKM) syndrome in UK Biobank: network-based study

By Long X, Li M, Li D et al.

Cardiovascular–kidney–metabolic (CKM) syndrome is a progressive, multisystem disorder whose real-world clinical trajectory remains incompletely characterized. This study aimed to characterize the temporal progression of CKM syndrome and its associated disease spectrum using large-scale, population-based diagnostic data. Utilizing first-occurrence diagnosis data from the UK Biobank, we implemented a sequential analytical pipeline to: (i) quantify pairwise disease associations; (ii) construct longitudinal progression maps for cardiovascular, renal, and metabolic conditions; (iii) identify pivotal diagnoses via unsupervised clustering and network centrality; and (iv) validate findings through a nested case–control study. Trajectory-defined subpopulations were analyzed to assess comorbidity-specific progression patterns. From 1,408,155 diagnostic records, 3351 unique disease trajectories were reconstructed. Essential hypertension was the most frequent initiating diagnosis (44.1% of trajectories). Chronic kidney disease (CKD) and type 2 diabetes emerged as frequently co-occurring conditions within the core diagnosis sets. In case–control analysis, CKD was associated with a significantly increased risk of transition to subsequent diagnoses (RR = 3.597; 95% CI 3.325–3.892). Among individuals with hypertension, those with coexisting type 2 diabetes (E11) had a significantly higher risk of developing CKD (N18) compared to those with atrial fibrillation (I48) or chronic ischaemic heart disease (I25) (HR = 2.944; 95% CI 2.760–3.139; P < 0.001). Our findings provide a detailed trajectory map of CKM syndrome based on UK Biobank data, describing hypertension-initiated, CKD-associated multimorbidity patterns. These findings offer a data-driven framework that may inform future mechanistic and interventional research targeting early stages of CKM progression.

doi.org/10.1038/s41598-026-49572-2 Open access PubMed 42014907 Populations