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Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury

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Abstract

Background

Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients.

Methods

Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects.

Results

Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81–0.98] for calprotectin and 0.73 (95 % CI 0.58–0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35–0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63–0.92) and 0.77 (CI 0.65–0.90), respectively.

Conclusions

Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.

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Acknowledgments

We thank Simone Voigt for her indefatigable efforts in this study. We are indebted to all children and their parents who participated in the study.

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Author notes

    Authors and Affiliations

    1. Department of Pediatrics I, University Children’s Hospital, Heidelberg, Germany

      Jens H. Westhoff, Alexander Fichtner & Burkhard Tönshoff

    2. Department of Neonatology, University Children’s Hospital, Heidelberg, Germany

      Sina Waldherr

    3. Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University of Bochum, Bochum, Germany

      Nikolaos Pagonas, Felix S. Seibert, Nina Babel, Frederic Bauer & Timm H. Westhoff

    Authors
    1. Jens H. Westhoff
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    2. Alexander Fichtner
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    Correspondence to Jens H. Westhoff or Timm H. Westhoff.

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    Funding

    The study was funded by the German Research Foundation (Research Unit FOR1368).

    Conflict of interest

    A patent for “Assay method for intrinsic acute kidney injury” has been granted.

    Ethics statement

    The study was approved by the ethics committee of the Medical Faculty of Heidelberg. Written informed consent was obtained from legal guardians of each patient with assent from the patient when appropriate. All clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki.

    Additional information

    Frederic Bauer and Timm H. Westhoff contributed equally to this work.

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    Westhoff, J.H., Fichtner, A., Waldherr, S. et al. Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury. Pediatr Nephrol 31, 2353–2363 (2016). https://doi.org/10.1007/s00467-016-3418-1

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    • DOI: https://doi.org/10.1007/s00467-016-3418-1

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