Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray

Rajit K. Basu, Stephen W. Standage, Natalie Z. Cvijanovich, Geoffrey L. Allen, Neal J. Thomas, Robert J. Freishtat, Nick Anas, Keith Meyer, Paul A. Checchia, Richard Lin, Thomas P. Shanley, Michael T. Bigham, Derek S. Wheeler, Prasad Devarajan, Stuart L. Goldstein, Hector R. Wong

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Abstract

Introduction: Septic-shock-associated acute kidney injury (SSAKI) carries high morbidity in the pediatric population. Effective treatment strategies are lacking, in part due to poor detection and prediction. There is a need to identify novel candidate biomarkers of SSAKI. The objective of our study was to determine whether microarray data from children with septic shock could be used to derive a panel of candidate biomarkers for predicting SSAKI.Methods: A retrospective cohort study compared microarray data representing the first 24 hours of admission for 179 children with septic shock with those of 53 age-matched normal controls. SSAKI was defined as a >200% increase of baseline serum creatinine, persistent to 7 days after admission.Results: Patients with SSAKI (n = 31) and patients without SSAKI (n = 148) were clinically similar, but SSAKI carried a higher mortality (45% vs. 10%). Twenty-one unique gene probes were upregulated in SSAKI patients versus patients without SSAKI. Using leave-one-out cross-validation and class prediction modeling, these probes predicted SSAKI with a sensitivity of 98% (95% confidence interval (CI) = 81 to 100) and a specificity of 80% (95% CI = 72 to 86). Serum protein levels of two specific genes showed high sensitivity for predicting SSAKI: matrix metalloproteinase-8 (89%, 95% CI = 64 to 98) and elastase-2 (83%, 95% CI = 58 to 96). Both biomarkers carried a negative predictive value of 95%. When applied to a validation cohort, although both biomarkers carried low specificity (matrix metalloproteinase-8: 41%, 95% CI = 28 to 50; and elastase-2: 49%, 95% CI = 36 to 62), they carried high sensitivity (100%, 95% CI = 68 to 100 for both).Conclusions: Gene probes upregulated in critically ill pediatric patients with septic shock may allow for the identification of novel candidate serum biomarkers for SSAKI prediction.

Original languageEnglish (US)
Article numberR273
JournalCritical Care
Volume15
Issue number6
DOIs
StatePublished - Nov 18 2011

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All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

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Basu, R. K., Standage, S. W., Cvijanovich, N. Z., Allen, G. L., Thomas, N. J., Freishtat, R. J., Anas, N., Meyer, K., Checchia, P. A., Lin, R., Shanley, T. P., Bigham, M. T., Wheeler, D. S., Devarajan, P., Goldstein, S. L., & Wong, H. R. (2011). Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray. Critical Care, 15(6), [R273]. https://doi.org/10.1186/cc10554