Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers

Authors

Eric A.J. Hoste
Peter A. McCullough
Kianoush Kashani
Lakhmir S. Chawla, George Washington UniversityFollow
Michael Joannidis
The Sapphire Investigators

Document Type

Journal Article

Publication Date

11-2014

Journal

Nephrology, Dialysis, Transplantation

Volume

Volume 29, Issue 11

Inclusive Pages

2054-2061

DOI

10.1093/ndt/gfu292

Keywords

Acute Kidney Injury--urine; Insulin-Like Growth Factor Binding Proteins--urine; Tissue Inhibitor of Metalloproteinase-2--urine

Abstract

Background

Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers.

Methods

We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2–3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the USA.

Results

One hundred subjects (14%) in Sapphire and 27 (18%) in Opal met the primary end point. The results of the Opal study replicated those of Sapphire. Relative risk (95% CI) in both studies for subjects testing at ≤0.3 versus >0.3–2 were 4.7 (1.5–16) and 4.4 (2.5–8.7), or 12 (4.2–40) and 18 (10–37) for ≤0.3 versus >2. For the 0.3 cutoff, sensitivity was 89% in both studies, and specificity 50 and 53%. For 2.0, sensitivity was 42 and 44%, and specificity 95 and 90%.

Conclusions

Urinary [TIMP-2]•[IGFBP7] values of 0.3 or greater identify patients at high risk and those >2 at highest risk for AKI and provide new information to support clinical decision-making.

Clinical Trials Registration

Clintrials.gov # NCT01209169 (Sapphire) and NCT01846884 (Opal).

Comments

Reproduced with permission of Oxford Journals. Nephrology, Dialysis, Transplantation.

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

APA Citation

Hoste, E. A. J., McCullough, P. A., Kashani, K., Chawla, L. S., Joannidis, M., et al. (2014). Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrology Dialysis Transplantation, 29(11), 2054–2061.

Peer Reviewed

1

Open Access

1