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

Abstract

BackgroundAcute 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).MethodsThis 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.ResultsAfter 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 1st 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.ConclusionsIn this pilot study we found that UCHI3L1 was a good biomarker for prediction of AKI stage ≥2 in adult ICU patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1192-x) contains supplementary material, which is available to authorized users.

Urinary cell cycle arrest biomarkers and chitinase 3-like protein 1 (CHI3L1) to detect acute kidney injury in the critically ill: a post hoc laboratory analysis on the FINNAKI cohort

“…In this multicenter validation study, we found that uCHI3L1 was markedly increased in general ICU patients who developed AKI stage 2 or 3 within a 24-h [15]. This study and previous studies on uCHI3L1 have demonstrated its use as a biomarker for diagnosis of AKI, and this with comparable performance to uNGAL and NephroCheck Risk® [8,9,[17][18][19]. CHI3L1 may also provide mechanistic insights in injury and repair mechanisms in the kidney.…”

“…The aim of this study was to evaluate uCHI3L1 as a biomarker for AKI in ICU patients included in the multicenter Finnish Acute Kidney Injury (FINNAKI) study and compare this to the NephroCheck Risk® score, the composite of the cell cycle arrest biomarkers TIMP-2 and IGFBP7. This may provide external validation to the biomarker uCHI3L1 that showed promise in our single-center study [8].…”

“…Given, the heterogeneous etiology of AKI and also different patients' baseline characteristics, different biomarkers may be complimentary to each other. Recently, we showed in a single-center prospective cohort study that urinary chitinase 3-like protein 1 (uCHI3L1) is a promising AKI biomarker in ICU patients when compared to urinary neutrophil gelatinaseassociated lipocalin (uNGAL) [8]. A subsequent study by our group in adult patients who underwent elective cardiac surgery demonstrated that in this specific setting, both uCHI3L1 and uNGAL showed inadequate predictive value for AKI [9].…”

Stability of glomerular and tubular renal injury biomarkers in canine urine after 4 years of storage

“…Even in human medicine, relatively few studies have evaluated the impact of preanalytical factors on urine proteins. 4,7 To our knowledge, only a single urine biomarker study, investigating the stability of RBP, albumin, Abstract. Urine biomarkers are sensitive indicators of early-stage renal injury, consequently, research in this area is expanding in both human and veterinary medicine.…”

Implementation of Proteomics Biomarkers in Nephrology: From Animal Models to Human Application?

“…In a single center study recruiting 181 severely ill adult ICU patients, urinary CHI3L1 predicted the development of AKI stage ≥2 (Kidney disease Improving global outcome (KDIGO) classification) with a reasonably well area under the curve (AUC) of 0.792 similar to urinary NGAL measured in the same study. Furthermore, increased urinary CHI3L1 abundance was associated to increased AKI severity after the event . In a subsequent study, the group reported the association of urinary CHI3L1 to the development of AKI after cardiac surgery involving 211 patients.…”