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Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?

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Abstract

Background

Early acute kidney injury (AKI) diagnosis is needed to pursue treatment trials. We evaluated cystatin C (CysC) as an early biomarker of serum creatinine (SCr)-AKI and an alternative to define AKI.

Methods

We studied 160 non-cardiac children in the intensive care unit (ICU). We measured daily CysC and SCr. AKI was staged by KDIGO (Kidney Disease: Improving Global Outcomes) guidelines using SCr and CysC (CysC-AKI). We calculated area under the curve (AUC) for (1) neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and urine CysC to diagnose SCr- and CysC-AKI; and (2) for CysC to diagnose SCr-AKI. We evaluated AKI associations with length of stay and ventilation duration.

Results

We found that 44 % of patients developed SCr-AKI; 32 % developed CysC-AKI. Early ICU NGAL was most diagnostic of CysC-AKI (AUC 0.69, 95% CI 0.54–0.84); IL-18 was most diagnostic for SCr-AKI (AUC 0.69 95% CI 0.55–0.82). Combining SCr and CysC-AKI definition led to higher biomarker diagnostic AUC’s. CysC-AKI was not more strongly associated with clinical outcomes. Early ICU CysC predicted SCr-AKI development (AUC 0.70, 95 % CI 0.53–0.89).

Conclusions

Our findings do not support replacing SCr by CysC to define AKI. Early ICU CysC predicts SCr-AKI development and combined SCr-CysC-AKI definition leads to stronger AKI biomarker associations.

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Acknowledgments

Dr. Zappitelli received institutional funding from the McGill University Health Centre Research Institute, the Kidney Research Scientist Core Education and National Training Program and the Fonds de Recherches en Santé du Quebec to support this work.

Disclosures

PD is a co-inventor on patents submitted for the use of NGAL as a biomarker of kidney injury.

JB is a co-inventor on patents involving KIM-1.

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Authors and Affiliations

  1. Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada

    Paola Lagos-Arevalo, Ana Palijan, Laura Vertullo, Ronald D. Gottesman & Michael Zappitelli

  2. Nephrology & Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Prasad Devarajan, Michael R. Bennett & Qing Ma

  3. Renal Division, Brigham’s and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Venkata Sabbisetti & Joseph V. Bonventre

  4. Montreal Children’s Hospital, 2300 Tupper, Room E-213, Montreal, QC, H3H1P3, Canada

    Michael Zappitelli

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  1. Paola Lagos-Arevalo
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  2. Ana Palijan
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  4. Prasad Devarajan
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  9. Ronald D. Gottesman
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Correspondence to Michael Zappitelli.

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Lagos-Arevalo, P., Palijan, A., Vertullo, L. et al. Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?. Pediatr Nephrol 30, 665–676 (2015). https://doi.org/10.1007/s00467-014-2987-0

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  • DOI: https://doi.org/10.1007/s00467-014-2987-0

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