Nephrology, Dialysis, Transplantation
Volume 29, Issue 11
Acute Kidney Injury--urine; Insulin-Like Growth Factor Binding Proteins--urine; Tissue Inhibitor of Metalloproteinase-2--urine
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.
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.
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%.
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).
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
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.
Reproduced with permission of Oxford Journals. Nephrology, Dialysis, Transplantation.