Table 4Clinical characteristics of the validation cohortTable Table55 provides the respective performance calculations for the two candidate biomarkers Tofacitinib Citrate Sigma in the validation cohort. Both candidate biomarkers were able to predict SSAKI with 100% sensitivity in the validation cohort. However, the markers carried limited positive predictive value. In the validation cohort, 35 patients had an MMP-8 level >11 ng/ml without sustained SSAKI. In these patients, eight (23%) met criteria for at least mild AKI (pediatric Risk, Injury, Failure, Loss, End-Stage kidney injury (RIFLE) Risk) for at least 1 day. Also in the validation cohort, 30 patients had an elastase-2 level >235 ng/ml without sustained SSAKI. OK Nine (30%) of these patients met at least pediatric RIFLE Risk criteria for at least 1 day.

Both biomarkers had negative predictive values for SSAKI of 100%, an important finding that adds clinical utility for practitioners treating patients who carry risks for developing severe AKI. Collectively, our results indicate that admission microarray data can be used to identify novel candidate biomarkers for SSAKI.Table 5Individual performance calculations of serum protein levels for predicting SSAKI in the validation cohortDiscussionWe have demonstrated that microarray data can be leveraged to identify gene expression patterns common in SSAKI. Although mRNA levels do not necessarily correlate with protein expression, analysis of MMP-8 and elastase-2 protein levels in the serum compartment indicates that our gene expression data can identify novel serum protein biomarkers for SSAKI.

Although sepsis is the most important predictor of AKI in critically ill patients [37,38], few clinical studies are dedicated to identifying the early phenotype of patients with SSAKI. Interrogation of several large databases of critically ill adult patients has yielded variables that may be predictive of SSAKI but are not consistently reliable (Table (Table6).6). The conclusions of these studies simply state that elevated proinflammatory markers portend adverse outcomes in acute kidney disease and death in patients with septic shock [39,40].Table 6Variables predictive of SSAKI in selected major adult trialsNGAL has received considerable attention as a potential biomarker for AKI.

NGAL derivation and validation studies were primarily performed in ischemic or nephrotoxic AKI Drug_discovery with great efficacy [13], while investigations of NGAL biomarker utility in SSAKI have demonstrated variable results. In the general ICU population, serum NGAL levels have not been reliably demonstrated to be specific for SSAKI (Table (Table6).6). We previously published that while day 1 serum NGAL levels were elevated, with acceptable sensitivity, in children who develop SSAKI, the specificity was quite poor (39%) [41]. A recent prospective cohort study of 632 adult ICU patients demonstrated that the likelihood ratio for AKI (RIFLE Failure) was 1.