Background: A translational study in renal transplantation suggested YKL-40, a chitinase 3-like-1 gene product,\nplays an important role in acute kidney injury (AKI) and repair, but data are lacking about this protein in urine from\nnative human kidneys.\nMethods: This is an ancillary study to a single-center, prospective observational cohort of patients with\nclinically-defined AKI according to AKI Network serum creatinine criteria. We determined the association of\nYKL ?40 ? 5 ng/ml, alone or combined with neutrophil gelatinase-associated lipocalin (NGAL), in urine collected\non the first day of AKI with a clinically important composite outcome (progression to higher AKI stage and/or\nin-hospital death).\nResults: YKL-40 was detectable in all 249 patients, but urinary concentrations were considerably lower than in\npreviously measured deceased-donor kidney transplant recipients. Seventy-two patients (29%) progressed or died\nin-hospital, and YKL-40 ? 5 ng/ml had an adjusted odds ratio (95% confidence interval) for the outcome of 3.4\n(1.5-7.7). The addition of YKL-40 to a clinical model for predicting the outcome resulted in a continuous net\nreclassification improvement of 29% (P = 0.04). In patients at high risk for the outcome based on NGAL concentrations\nin the upper quartile, YKL-40 further partitioned the cohort into moderate-risk and very high-risk groups.\nConclusions: Urine YKL-40 is associated with AKI progression and/or death in hospitalized patients and improves\nclinically determined risk reclassification. Combining YKL-40 with other AKI biomarkers like NGAL may further delineate\nprogression risk, though additional studies are needed to determine whether YKL-40 has general applicability and to\ndefine its association with longer-term outcomes in AKI.
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