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

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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 %).

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Abbreviations

ADHF:

Acute decompensated heart failure

AUC:

Area under the curve

BNP:

B-type natriuretic peptide

CCHMC:

Cincinnati Children’s Hospital Medical Center

CGCC:

Cincinnati Genomic Control Cohort

CHF:

Congestive heart failure

CKD:

Chronic kidney disease

CRS:

Cardiorenal syndrome

DCM:

Dilated cardiomyopathy

eGFR:

Estimated glomerular filtration rate

IL-18:

Interleukin 18

IQR:

Interquartile range

KIM-1:

Kidney injury molecule-1

L-FABP:

Liver-fatty acid binding protein

LV:

Left ventricular

LVEDD:

Left ventricular end-diastolic dimension

LVEF:

Left ventricular ejection fraction

LVESD:

Left ventricular end-systolic dimension

LVFS:

Left ventricular fractional shortening

LVNC:

Left ventricular non-compaction

NGAL:

Neutrophil gelatinase-associated lipocalin

OR:

Odds ratio

ROC:

Receiver operating characteristic

SCr:

Serum creatinine

TIM:

Tubular injury markers

uCr:

Urinary creatinine

uMAlb:

Urinary microalbumin

uPr:

Urinary protein

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Center for Acute Care Nephrology, Cincinnati, OH, USA

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

  2. Sidra Medical and Research Center, Doha, Qatar

    Ahmad Kaddourah

  3. The Heart Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA

    Stuart L. Goldstein & John L. Jefferies

  4. Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA

    Rajit Basu

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  1. Ahmad Kaddourah
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  2. Stuart L. Goldstein
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  3. Rajit Basu
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  7. Michael R. Bennett
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  9. John L. Jefferies
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Corresponding author

Correspondence to John L. Jefferies.

Ethics declarations

The study was approved by the Cincinnati Children’s Hospital Medical Center Institutional Review Board. Predefined clinical variables were extracted from medical records following provision of informed consent by the patient caregiver.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Kaddourah, A., Goldstein, S.L., Basu, R. et al. Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function: a pilot study. Pediatr Nephrol 31, 1637–1645 (2016). https://doi.org/10.1007/s00467-016-3360-2

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