Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

Abstract

Background: Individuals with chronic kidney disease (CKD) have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods: We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age-and sex matched healthy volunteers. Among COMBINE participants, we examined the associations of estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results: Mean (standard deviation [SD]) age of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years. The mean (SD) baseline eGFR in COMBINE participants was 32.1 (8.0) and 85.9 (16.0) ml/ min/1.73m2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3 - 540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared to healthy volunteers (β estimate -0.13 CKD vs. non-CKD, 95% confidence interval [CI] -0.24, -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β-estimate per 1 unit increase in natural log UACR -0.06, 95% CI -0.09, -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions: Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction assessed by mitral valve E/A ratio in individuals with CKD with and without clinical CVD, but was not associated with change in any cMRI parameter.