Ahmad Kaddourah1,2, Stuart L Goldstein1,3, Rajit Basu4, Edwards J Nehus1, Tara C Terrell1, Lori Brunner1, Michael R Bennett1, Christopher Haffner1, John L Jefferies5,6. 1. Center for Acute Care Nephrology, Cincinnati, OH, USA. 2. Sidra Medical and Research Center, Doha, Qatar. 3. The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA. 4. Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA. 5. Center for Acute Care Nephrology, Cincinnati, OH, USA. john.jefferies@cchmc.org. 6. The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA. john.jefferies@cchmc.org.
Abstract
BACKGROUND: Evolving data suggest tubular injury markers (TIM) to be diagnostic and prognostic biomarkers of kidney injury in adults with chronic cardiac dysfunction. Such data are not well delineated in asymptomatic children with cardiomyopathy. This study sought to evaluate kidney involvement in children with left ventricular (LV) systolic dysfunction. METHODS: We conducted a cross-sectional case-control study in 61 asymptomatic children (aged 1.7-21.9 years) with dilated cardiomyopathy (DCM) and LV ejection fraction (LVEF) < 55 %. Routine conventional kidney function markers and the following urinary TIM were measured: KIM-1, IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and L-FABP. Characteristics and TIM data of cases were compared with those of 61 age- and gender-matched healthy controls. RESULTS: Children with DCM had higher TIM concentrations compared with controls for IL-18 (28.2 pg/mg, IQR [15.9-42.5] vs19.0 [12.6-28.6], p < 0.001), NGAL (13.2 ng/mg [6.5-44.3] vs 8.3 [3.1-17.5], p = 0.01), and KIM-1 (386 pg/mg (248-597) vs 307 [182-432], p = 0.02). All conventional kidney function markers were within normal limits in the DCM cohort. A combined model using cut-off values of KIM-1 ≥ 235, IL-18 ≥ 17.5, and (BNP) > 15 pg/ml resulted in distinction between patients with mildly depressed LV (55 > LVEF ≥ 45) and those with LVEF < 45 %. The sensitivity of this model was ≥80 % when any of the cut-off values was met and specificity 83 % when all cut-off values were met. CONCLUSIONS: Our data suggest that asymptomatic children with LVEF < 55 % might have subclinical kidney injury that cannot be detected with conventional kidney function markers. TIM in conjunction with other cardiac function markers may be utilized to distinguish asymptomatic children with DCM and moderate or worse LV dysfunction (LFEV < 45 %) from those with mild LV dysfunction (55 > LVEF ≥ 45 %).
BACKGROUND: Evolving data suggest tubular injury markers (TIM) to be diagnostic and prognostic biomarkers of kidney injury in adults with chronic cardiac dysfunction. Such data are not well delineated in asymptomatic children with cardiomyopathy. This study sought to evaluate kidney involvement in children with left ventricular (LV) systolic dysfunction. METHODS: We conducted a cross-sectional case-control study in 61 asymptomatic children (aged 1.7-21.9 years) with dilated cardiomyopathy (DCM) and LV ejection fraction (LVEF) < 55 %. Routine conventional kidney function markers and the following urinary TIM were measured: KIM-1, IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and L-FABP. Characteristics and TIM data of cases were compared with those of 61 age- and gender-matched healthy controls. RESULTS:Children with DCM had higher TIM concentrations compared with controls for IL-18 (28.2 pg/mg, IQR [15.9-42.5] vs19.0 [12.6-28.6], p < 0.001), NGAL (13.2 ng/mg [6.5-44.3] vs 8.3 [3.1-17.5], p = 0.01), and KIM-1 (386 pg/mg (248-597) vs 307 [182-432], p = 0.02). All conventional kidney function markers were within normal limits in the DCM cohort. A combined model using cut-off values of KIM-1 ≥ 235, IL-18 ≥ 17.5, and (BNP) > 15 pg/ml resulted in distinction between patients with mildly depressed LV (55 > LVEF ≥ 45) and those with LVEF < 45 %. The sensitivity of this model was ≥80 % when any of the cut-off values was met and specificity 83 % when all cut-off values were met. CONCLUSIONS: Our data suggest that asymptomatic children with LVEF < 55 % might have subclinical kidney injury that cannot be detected with conventional kidney function markers. TIM in conjunction with other cardiac function markers may be utilized to distinguish asymptomatic children with DCM and moderate or worse LV dysfunction (LFEV < 45 %) from those with mild LV dysfunction (55 > LVEF ≥ 45 %).
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