Related Experiment Video

Updated: Jun 20, 2026

Assessment of Vascular Function in Patients With Chronic Kidney Disease
08:50

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Published on: June 16, 2014

Cardiovascular-Kidney-Metabolic Multimorbidity Burden and Phenotype Differentially Influence Cardiovascular and Renal

William R Marshall1,2, Rajkumar Chinnadurai3,4, Darren Green3,4

  • 1Division of Cardiovascular Sciences, University of Manchester, Manchester, UK, william.marshall-6@postgrad.manchester.ac.uk.

Cardiorenal Medicine
|June 18, 2026
PubMed

Insights

Increasing cardiovascular-kidney-metabolic (CKM) conditions predict cardiovascular events and mortality in chronic kidney disease (CKD) patients. However, kidney disease progression is more linked to specific phenotypes, especially diabetic kidney disease.

Area of Science:

  • Nephrology
  • Cardiology
  • Metabolic Diseases

Background:

  • Chronic kidney disease (CKD) often coexists with cardiovascular disease (CVD), diabetes, and obesity, linked by shared pathways within the American Heart Association's cardiovascular-kidney-metabolic (CKM) construct.
  • It remains unclear if adverse outcomes in CKD stem from overall multimorbidity or distinct CKM phenotypes.

Purpose of the Study:

  • To investigate whether cumulative multimorbidity burden or specific CKM disease phenotypes are the primary drivers of adverse cardiovascular and renal outcomes in patients with non-dialysis-dependent CKD.

Main Methods:

  • Retrospective longitudinal cohort study of 2,003 patients with non-dialysis-dependent CKD and at least one other CKM comorbidity.
  • Patients were categorized by CKM multimorbidity burden (2, 3, or 4 conditions) and predefined CKM phenotypes.
  • Outcomes included major adverse cardiovascular events (MACE), composite kidney endpoint (CKE), and all-cause mortality, analyzed using multivariable time-to-event models.

Main Results:

  • Higher CKM multimorbidity burden (4 conditions vs. 2) significantly increased MACE risk (HR 1.93).
  • The CKD-CVD-diabetes-obesity phenotype showed the highest MACE risk.
  • Diabetes-containing phenotypes were linked to higher CKE risk, while multimorbidity burden had limited predictive value for kidney progression.
  • The CKD-diabetes-CVD phenotype exhibited the highest all-cause mortality.

Conclusions:

  • Increasing CKM multimorbidity burden predicts cardiovascular events and mortality, aligning with the AHA staging framework.
  • Kidney progression is more strongly associated with specific disease phenotypes, particularly diabetic kidney disease.
  • This cardiovascular-renal dissociation suggests refining CKM staging by phenotype could improve risk stratification in advanced CKD.
Abstract

Keywords:
Cardiovascular-kidney-metabolic constructEstimated glomerular filtration rate slopeMajor adverse cardiovascular eventMultimorbidity

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