Document Type
Journal Article
Publication Date
6-2016
Journal
Nephrology Dialysis Transplantation
DOI
10.1093/ndt/gfw238
Abstract
Background The NEPROCHECK test (Astute Medical, San Diego, CA, USA) combines urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) to identify patients at high risk for acute kidney injury (AKI). In a US Food and Drug Administration registration trial (NCT01573962), AKI was determined by a three-member clinical adjudication committee. The objectives were to examine agreement among adjudicators as well as between adjudicators and consensus criteria for AKI and to determine the relationship of biomarker concentrations and adjudicator agreement.
Methods Subjects were classified as AKI 3/3, 2/3, 1/3 or 0/3 according to the proportion of adjudicators classifying the case as AKI. Subjects were classified as Kidney Disease: Improving Global Outcomes (KDIGO) AKI(+) when stage 2 or 3 AKI criteria were met.
Results Concordance between adjudicators and between adjudicators and KDIGO criteria were lower for AKI than non-AKI subjects [78.9 versus 97.3% (P < 0.001) and 91.5 versus 97.9% (P = 0.01)]. Subjects who were AKI 3/3 or 2/3 but KDIGO AKI(−) had higher median [TIMP-2]•[IGFBP7] compared with those who were AKI-1/3 or 0/3 but KDIGO AKI(+) {2.78 [interquartile range (IQR) 2.33–3.56] versus 0.52 [IQR 0.26–1.64]; P = 0.008}. [TIMP-2]•[IGFBP7] levels were highest in patients with AKI 3/3 and lowest in AKI 0/3, whereas AKI 2/3 and 1/3 exhibited intermediate values.
Conclusions In this analysis, urine [TIMP-2]•[IGFBP7] levels correlated to clinically adjudicated AKI better than to KDIGO criteria. Furthermore, in difficult cases where adjudicators overruled KDIGO criteria, the biomarker test discriminated well. This study highlights the importance of clinical adjudication of AKI for biomarker studies and lends further support for the value of urine [TIMP-2]•[IGFBP7].
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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
APA Citation
Liu, K. D., Vijayan, A., Rosner, M. H., Shi, J., Chawla, L. S., & Kellum, J. A. (2016). Clinical adjudication in acute kidney injury studies: findings from the pivotal TIMP-2*IGFBP7 biomarker study. Nephrology Dialysis Transplantation, (). http://dx.doi.org/10.1093/ndt/gfw238
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Oxford University Press. Nephrology Dialysis Transplantation.