Urinary chitinase 3-like protein 1 for early diagnosis of acute kidney injury: a prospective cohort study in adult critically ill patients.

BACKGROUND: Acute kidney injury (AKI) occurs frequently and adversely affects patient and kidney outcomes, especially when its severity increases from stage 1 to stages 2 or 3. Early interventions may counteract such deterioration, but this requires early detection. Our aim was to evaluate whether the novel renal damage biomarker urinary chitinase 3-like protein 1 (UCHI3L1) can detect AKI stage ≥ 2 more early than serum creatinine and urine output, using the respective Kidney Disease | Improving Global Outcomes (KDIGO) criteria for definition and classification of AKI, and compare this to urinary neutrophil gelatinase-associated lipocalin (UNGAL). METHODS: This was a translational single-center, prospective cohort study at the 22-bed surgical and 14-bed medical intensive care units (ICU) of Ghent University Hospital. We enrolled 181 severely ill adult patients who did not yet have AKI stage ≥ 2 based on the KDIGO criteria at time of enrollment. The concentration of creatinine (serum, urine) and CHI3L1 (serum, urine) was measured at least daily, and urine output hourly, in the period from enrollment till ICU discharge with a maximum of 7 ICU-days. The concentration of UNGAL was measured at enrollment. The primary endpoint was the development of AKI stage ≥ 2 within 12 h after enrollment. RESULTS: After enrollment, 21 (12%) patients developed AKI stage ≥ 2 within the next 7 days, with 6 (3%) of them reaching this condition within the first 12 h. The enrollment concentration of UCHI3L1 predicted the occurrence of AKI stage ≥ 2 within the next 12 h with a good AUC-ROC of 0.792 (95% CI: 0.726-0.849). This performance was similar to that of UNGAL (AUC-ROC of 0.748 (95% CI: 0.678-0.810)). Also, the samples collected in the 24-h time frame preceding diagnosis of the 1(st) episode of AKI stage ≥ 2 had a 2.0 times higher (95% CI: 1.3-3.1) estimated marginal mean of UCHI3L1 than controls. We further found that increasing UCHI3L1 concentrations were associated with increasing AKI severity. CONCLUSIONS: In this pilot study we found that UCHI3L1 was a good biomarker for prediction of AKI stage ≥ 2 in adult ICU patients.

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

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.

Airway, but not serum or urinary, levels of YKL-40 reflect inflammation in early cystic fibrosis lung disease.

BACKGROUND: Cystic fibrosis (CF) lung disease begins in early life and is progressive with the major risk factor being an exaggerated inflammatory response. Currently, assessment of neutrophilic inflammation in early cystic fibrosis (CF) lung disease relies on bronchoalveolar lavage (BAL). The chitinase-like protein YKL-40 is raised in sputum and serum of adults with CF. We investigated YKL-40 in BAL, serum and urine to determine whether this reflected inflammation and infection in young children with CF. METHODS: YKL-40 was measured in matched samples of BAL, serum and urine obtained from 36 infants and young children with CF participating in an early surveillance program. Levels were compared to clinical data and markers of inflammation detected in the lung. RESULTS: YKL-40 in BAL correlated with pulmonary infection [ß=1.30 (SE 0.34), p < 0.001] and BAL markers of inflammation [macrophage number: r2 = 0.34, p < 0.001; neutrophil number: r2 = 0.74, p < 0.001; neutrophil elastase: r2 = 0.47, p < 0.001; CXCL8: r2 = 0.45, p < 0.001; IL-ß: r2 = 0.62, p < 0.001]. YKL-40 was detectable in serum but levels did not correlate with BAL levels in the same individuals (r2 = 0.04, p = 0.14) or with inflammatory markers. YKL-40 was below the limit of detection in urine (30 pg/ml). CONCLUSIONS: This study demonstrates that levels of the chitinase-like protein YKL-40 reflect airway inflammation and infection in early CF lung disease. The lack of increased YKL-40 in serum in the absence of systemic inflammation limits the benefit of this potential biomarker in early disease.

Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation.

Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness.

Prognostic effect of serum and tissue YKL-40 levels in bladder cancer.

OBJECTIVES: YKL-40 is a novel inflammatory serum protein shown to be associated with the presence and prognosis of several malignancies. However, its prognostic relevance has not yet been analyzed in bladder cancer (BC). Therefore, the aim of this study was to assess the tissue, serum, and urinary levels of YKL-40 and their prognostic value in BC. METHODS AND MATERIALS: YKL-40 gene expression levels were analyzed in frozen tissue samples of 91 patients with BC; YKL-40 concentrations were measured in 120 serum (101 patients with BC and 19 controls) and 154 urine samples (125 patients with BC and 29 controls). In 16 cases, corresponding serum samples collected before and after radical cystectomy were analyzed for YKL-40. Results were correlated with clinicopathological parameters and follow-up data. RESULTS: YKL-40 gene expressions and serum concentrations were higher in patients with BC compared with controls; however, urinary YKL-40 levels remained under the detection limit in both patients and controls. Higher tissue gene expressions and serum concentrations were associated with poor patients' survival in the univariable analysis (P = 0.037 and 0.022, respectively), but only high YKL-40 serum levels proved to be independent prognostic factors in BC (hazard ratio = 1.755, 95% CI: 1.014-3.039, P = 0.045). We found no significant difference between preoperative and postoperative serum concentrations of YKL-40. CONCLUSIONS: YKL-40 serum levels are associated with the presence of BC and poor patients' survival. The independent prognostic relevance of YKL-40 is of particular interest in patients with muscle-invasive BC treated with radical surgery. Our data suggest that BC tissue is not the main source of serum YKL-40 levels.

Clinical implication of plasma and urine YKL-40, as a proinflammatory biomarker, on early stage of nephropathy in type 2 diabetic patients.

OBJECTIVE: Chronic inflammation has emerged as being a key pathophysiology in the early stages of diabetic nephropathy. YKL-40 has been established as an inflammatory marker in chronic inflammation. The aim of this study was to evaluate the association of plasma and urine YKL-40 with albuminuria in the early stage of type 2 diabetic nephropathy. DESIGN AND METHODS: A total of 75 type 2 diabetic patients and 22 nondiabetic controls with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2) were enrolled. Plasma and urine concentrations of YKL-40 were analyzed by ELISA kit. RESULTS: The plasma levels of YKL-40 were significantly higher in the normoalbuminuric group with diabetes than in the control group, and increased with increasing severity of albuminuria among diabetes. However, urine YKL-40 was only increased in macroalbuminuric state. Plasma YKL-40 was positively correlated with urine YKL-40 (r=0.291, P=0.011). Urinary albumin significantly correlated with both plasma and urine YKL-40 in a univariate analysis. After adjusting for several confounding factors, plasma YKL-40 was significantly correlated with albuminuria (r=0.359; P=0.001), whereas urine YKL-40 did not show significant correlation with albuminuria (r=0.128, P=0.241). CONCLUSIONS: Although urine YKL-40 has a limited role, plasma YKL-40, as an proinflammatory marker, was an independent factor associated with albuminuria in early stage of nephropathy in type 2 diabetes and might have an useful role as a noninvasive marker for the early diabetic nephropathy detection.