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Open Access Research article

Urine YKL-40 is associated with progressive acute kidney injury or death in hospitalized patients

Isaac E Hall12, Edward P Stern3, Lloyd G Cantley1, Jack A Elias4 and Chirag R Parikh12*

Author Affiliations

1 Section of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

2 Program of Applied Translational Research, Yale School of Medicine, 60 Temple Street, 6th Floor, Suite 6C, New Haven, CT 06510, USA

3 Centre for Nephrology, University College London/Royal Free London NHS Foundation Trust, London, UK

4 Division of Biology and Medicine, Brown University, Providence, RI, USA

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BMC Nephrology 2014, 15:133  doi:10.1186/1471-2369-15-133

Published: 15 August 2014

Abstract

Background

A translational study in renal transplantation suggested YKL-40, a chitinase 3-like-1 gene product, plays an important role in acute kidney injury (AKI) and repair, but data are lacking about this protein in urine from native human kidneys.

Methods

This is an ancillary study to a single-center, prospective observational cohort of patients with clinically-defined AKI according to AKI Network serum creatinine criteria. We determined the association of YKL -40 ≥ 5 ng/ml, alone or combined with neutrophil gelatinase-associated lipocalin (NGAL), in urine collected on the first day of AKI with a clinically important composite outcome (progression to higher AKI stage and/or in-hospital death).

Results

YKL-40 was detectable in all 249 patients, but urinary concentrations were considerably lower than in previously measured deceased-donor kidney transplant recipients. Seventy-two patients (29%) progressed or died in-hospital, and YKL-40 ≥ 5 ng/ml had an adjusted odds ratio (95% confidence interval) for the outcome of 3.4 (1.5-7.7). The addition of YKL-40 to a clinical model for predicting the outcome resulted in a continuous net reclassification improvement of 29% (P = 0.04). In patients at high risk for the outcome based on NGAL concentrations in the upper quartile, YKL-40 further partitioned the cohort into moderate-risk and very high-risk groups.

Conclusions

Urine YKL-40 is associated with AKI progression and/or death in hospitalized patients and improves clinically determined risk reclassification. Combining YKL-40 with other AKI biomarkers like NGAL may further delineate progression risk, though additional studies are needed to determine whether YKL-40 has general applicability and to define its association with longer-term outcomes in AKI.

Keywords:
Acute kidney injury; Biomarker; BRP-39; Chitinase 3-like-1; Net reclassification improvement; YKL-40