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Association of Kidney Tubule Biomarkers With Cardiac Structure and Function in the Multiethnic Study of
Nicholas Wettersten1, Ronit Katz2, Jason H Greenberg3
1Cardiology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California; Division of Cardiology, Department of Medicine, University of California San Diego, San Diego, California.
Insights
Kidney tubule health impacts heart structure and function, independent of kidney filtration markers. Biomarkers of tubule injury predict cardiac abnormalities, suggesting a direct link beyond estimated glomerular filtration rate and albuminuria.
Area of Science:
- Nephrology and Cardiology
- Biomarker Discovery
- Cardiorenal Syndrome
Background:
- Glomerular filtration rate (eGFR) and albuminuria are established markers of kidney disease linked to cardiovascular disease (CVD).
- The role of kidney tubule injury and inflammation in cardiac abnormalities is less understood.
- Existing research often focuses on glomerular markers, potentially overlooking tubule-specific contributions to cardiorenal health.
Purpose of the Study:
- To investigate the association between biomarkers of kidney tubule injury, function, and systemic inflammation with cardiac structural abnormalities.
- To determine if these kidney biomarkers predict cardiac dysfunction independently of established markers like eGFR and albuminuria.
- To explore novel pathways linking kidney health to cardiovascular structure and function.
Main Methods:
- Cross-sectional analysis of 393 participants from the Multi-Ethnic Study of Atherosclerosis without pre-existing diabetes, CVD, or chronic kidney disease.
- Assessment of 12 biomarkers related to kidney tubule injury, function, and inflammation.
- Cardiac magnetic resonance imaging (MRI) to measure left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF).
- Linear regression models used to assess associations, adjusting for CVD risk factors, eGFR, and albuminuria.
Main Results:
- Elevated plasma soluble urokinase plasminogen activator receptor (suPAR) was associated with increased LVmvr and decreased LVEF.
- Plasma monocyte chemoattractant protein 1 (MCP-1) showed a similar association with higher LVmvr.
- Increased plasma chitinase-3-like protein 1 (CHI3L1) and urine alpha-1-microglobulin (A1M) were linked to lower LVEF.
- These associations remained significant even after accounting for eGFR and albuminuria.
Conclusions:
- Kidney tubule health, assessed by specific biomarkers, is significantly associated with cardiac structural abnormalities and dysfunction.
- These findings suggest that kidney tubule injury and inflammation contribute to cardiac issues independently of glomerular markers.
- Targeting kidney tubule health may offer novel therapeutic strategies for preventing cardiovascular complications in at-risk populations.
Abstract:
Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m2; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.
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