TY - JOUR
T1 - Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function
T2 - a pilot study
AU - Kaddourah, Ahmad
AU - Goldstein, Stuart L.
AU - Basu, Rajit
AU - Nehus, Edwards J.
AU - Terrell, Tara C.
AU - Brunner, Lori
AU - Bennett, Michael R.
AU - Haffner, Christopher
AU - Jefferies, John L.
N1 - Funding Information:
The project described used the REDCap data application, which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant UL1 TR000002. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.
Publisher Copyright:
© 2016, IPNA.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 %).
AB - 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 %).
KW - Cardiomyopathy
KW - Cardiorenal syndrome
KW - Children
KW - Chronic kidney disease
KW - Tubular injury markers
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U2 - 10.1007/s00467-016-3360-2
DO - 10.1007/s00467-016-3360-2
M3 - Article
C2 - 27139898
AN - SCOPUS:84965082692
VL - 31
SP - 1637
EP - 1645
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 10
ER -