Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function

a pilot study

Ahmad Kaddourah, Stuart L. Goldstein, Rajit Basu, Edwards J. Nehus, Tara C. Terrell, Lori Brunner, Michael R. Bennett, Christopher Haffner, John Jefferies

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 %).

Original languageEnglish (US)
Pages (from-to)1637-1645
Number of pages9
JournalPediatric Nephrology
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

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Left Ventricular Function
Kidney
Wounds and Injuries
Dilated Cardiomyopathy
Left Ventricular Dysfunction
Cardiomyopathies
Stroke Volume
Cross-Sectional Studies
Biomarkers

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function : a pilot study. / Kaddourah, Ahmad; Goldstein, Stuart L.; Basu, Rajit; Nehus, Edwards J.; Terrell, Tara C.; Brunner, Lori; Bennett, Michael R.; Haffner, Christopher; Jefferies, John.

In: Pediatric Nephrology, Vol. 31, No. 10, 01.10.2016, p. 1637-1645.

Research output: Contribution to journalArticle

Kaddourah, Ahmad ; Goldstein, Stuart L. ; Basu, Rajit ; Nehus, Edwards J. ; Terrell, Tara C. ; Brunner, Lori ; Bennett, Michael R. ; Haffner, Christopher ; Jefferies, John. / Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function : a pilot study. In: Pediatric Nephrology. 2016 ; Vol. 31, No. 10. pp. 1637-1645.
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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 {\%}).",
author = "Ahmad Kaddourah and Goldstein, {Stuart L.} and Rajit Basu and Nehus, {Edwards J.} and Terrell, {Tara C.} and Lori Brunner and Bennett, {Michael R.} and Christopher Haffner and John Jefferies",
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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

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 %).

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