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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

(2020) CRITICAL CARE. 24(1).
Author
Organization
Abstract
Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)center dot insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk (R). Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1 center dot TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk (R) cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk (R) cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk (R) had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.
Keywords
Critical Care and Intensive Care Medicine, Acute kidney injury, Biological markers, Biomarkers, Chitinase, Lipocalins, Intensive care, NephroCheck, YKL-40, INFLAMMATION, EPIDEMIOLOGY, GUIDELINES, FAILURE, SEPSIS, MARKER

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MLA
Hoste, Eric, et al. “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.” CRITICAL CARE, vol. 24, no. 1, 2020, doi:10.1186/s13054-020-02867-w.
APA
Hoste, E., The FINNAKI Study Group, [missing], Vaara, S. T., De Loor, J., Haapio, M., Nuytinck, L., … Meyer, E. (2020). 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. CRITICAL CARE, 24(1). https://doi.org/10.1186/s13054-020-02867-w
Chicago author-date
Hoste, Eric, [missing] The FINNAKI Study Group, Suvi T. Vaara, Jorien De Loor, Mikko Haapio, Lieve Nuytinck, Kristel Demeyere, Ville Pettilä, and Evelyne Meyer. 2020. “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.” CRITICAL CARE 24 (1). https://doi.org/10.1186/s13054-020-02867-w.
Chicago author-date (all authors)
Hoste, Eric, [missing] The FINNAKI Study Group, Suvi T. Vaara, Jorien De Loor, Mikko Haapio, Lieve Nuytinck, Kristel Demeyere, Ville Pettilä, and Evelyne Meyer. 2020. “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.” CRITICAL CARE 24 (1). doi:10.1186/s13054-020-02867-w.
Vancouver
1.
Hoste E, The FINNAKI Study Group [missing], Vaara ST, De Loor J, Haapio M, Nuytinck L, et al. 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. CRITICAL CARE. 2020;24(1).
IEEE
[1]
E. Hoste et al., “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,” CRITICAL CARE, vol. 24, no. 1, 2020.
@article{8661541,
  abstract     = {Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)center dot insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk (R). Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1 center dot TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk (R) cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk (R) cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk (R) had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.},
  articleno    = {144},
  author       = {Hoste, Eric and The FINNAKI Study Group, [missing] and Vaara, Suvi T. and De Loor, Jorien and Haapio, Mikko and Nuytinck, Lieve and Demeyere, Kristel and Pettilä, Ville and Meyer, Evelyne},
  issn         = {1466-609X},
  journal      = {CRITICAL CARE},
  keywords     = {Critical Care and Intensive Care Medicine,Acute kidney injury,Biological markers,Biomarkers,Chitinase,Lipocalins,Intensive care,NephroCheck,YKL-40,INFLAMMATION,EPIDEMIOLOGY,GUIDELINES,FAILURE,SEPSIS,MARKER},
  language     = {eng},
  number       = {1},
  pages        = {10},
  title        = {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},
  url          = {http://dx.doi.org/10.1186/s13054-020-02867-w},
  volume       = {24},
  year         = {2020},
}

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