Associations of Biomarkers of Kidney Tubule Health, Injury, and Inflammation with Left Ventricular Hypertrophy in Children with CKD

KEY POINTS: Higher plasma and urine kidney injury molecule-1, urine monocyte chemoattractant protein-1, and lower urine alpha-1-microglobulin were associated with left ventricular hypertrophy, even after adjustment for confounders. Biomarkers of tubular injury, dysfunction, and inflammation may indicate the severity of kidney pathology and are associated with left ventricular hypertrophy. BACKGROUND: Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. We have shown that several plasma and urine biomarkers are associated with increased risk of CKD progression. As CKD is associated with LVH, we sought to investigate the association between the biomarkers and LVH. METHODS: In the CKD in Children Cohort Study, children aged 6 months to 16 years with an eGFR of 30–90 ml/min per 1.73 m(2) were enrolled at 54 centers in the United States and Canada. We measured plasma biomarkers kidney injury molecule-1 (KIM-1), tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase-type plasminogen activator receptor and urine KIM-1, monocyte chemoattractant protein-1 (MCP-1), YKL-40, alpha-1-microglobulin (alpha-1m), and epidermal growth factor in stored plasma and urine collected 5 months after enrollment. Echocardiograms were performed 1 year after enrollment. We assessed the cross-sectional association between the log(2) biomarker levels and LVH (left ventricular mass index greater than or equal to the 95th percentile) using a Poisson regression model, adjusted for age, sex, race, body mass index, hypertension, glomerular diagnosis, urine protein-to-creatinine ratio, and eGFR at study entry. RESULTS: Among the 504 children, LVH prevalence was 12% (n=59) 1 year after enrollment. In a multivariable-adjusted model, higher plasma and urine KIM-1 and urine MCP-1 concentrations were associated with a higher prevalence of LVH (plasma KIM-1 prevalence ratio [PR] per log(2): 1.27, 95% confidence interval [CI], 1.02 to 1.58; urine KIM-1 PR: 1.21, 95% CI, 1.11 to 1.48; and urine MCP-1 PR: 1.18, 95% CI, 1.04 to 1.34). After multivariable adjustment for covariates, lower urine alpha-1m was also associated with a higher prevalence of LVH (PR: 0.90, 95% CI, 0.82 to 0.99). CONCLUSIONS: Higher plasma and urine KIM-1, urine MCP-1, and lower urine alpha-1m were each associated with LVH prevalence in children with CKD. These biomarkers may better inform risk and help elucidate the pathophysiology of LVH in pediatric CKD.