The Bidirectional Association of Chronic Kidney Disease, Type 2 Diabetes, Atherosclerotic Cardiovascular Disease, and Heart Failure: The Cardio–Renal–Metabolic Syndrome

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Abstract
Background: The cardiometabolic syndrome focuses on the association between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), whereas the cardiorenal syndrome focuses on the association between chronic kidney disease (CKD) and heart failure (HF). Consideration of these two syndromes as a single entity has not been well described. Methods: We used the electronic medical records of Kaiser Permanente Northwest to identify 387,985 members aged 18+ years with a serum creatinine measured from 2005 to 2017. If the estimated glomerular filtration rate was 2 , we required a second confirmatory measurement 3–12 months later. Patients were followed through 2019. We calculated the age- and gender-adjusted incidence and progression of CKD per 1000 person-years using generalized estimating equations. We used Cox proportional hazard models to assess the time-dependent effect of each condition on incidence of the other conditions. Results: CKD incidence rates were highest in patients with T2DM, ASCVD, and HF (27.0 per 1000 person-years [95% confidence interval (CI) 24.8–29.4] vs. 5.9 [5.8–6.0] in patients with none of these conditions). Similar results were obtained for CKD progression (309.0, 283.9–336.4 for all three conditions vs. 147.9, 143.3–152.4 for no condition). In time-dependent models, all three conditions were independently associated with CKD incidence, being highest for HF (hazard ratio 2.14, 95% CI 2.07–2.21). All relationships between CKD, T2DM, ASCVD, and HF were significant and bidirectional. Conclusions: The presence of CKD, T2DM, HF, and ASCVD each conveys risk on the others. A cardiometabolic renal syndrome comprising these conditions may be an important disease entity that requires a comprehensive treatment approach.

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