Importantly, the pathophysiology of SSAKI may be unique from that of ischemic or nephrotoxic AKI [18]. Therapies aiming to restore renal perfusion in ischemic AKI [19-21] have not been selleck chem inhibitor demonstrated to be particularly effective and may be even less effective in SSAKI, a process that may not be secondary to impaired glomerular preload. Persistent SSAKI may fall into the class of fluid-unresponsive AKI [22]. Renal replacement therapy has been used as therapy for AKI and data exist demonstrating that initiation prior to accumulation of excessive fluid overload may improve outcomes [23,24]. The aggregate data, however, show that patients with SSAKI have consistently increased mortality, even with early renal replacement therapy initiation [25,26].

The modest efficacy of biomarkers at identifying SSAKI also underscores the notion that the pathophysiology of SSAKI is unique from other etiologies of AKI. There is a need to identify novel candidate biomarkers of SSAKI, which would expedite early treatment aimed at preventing the effects of this highly morbid complication of sepsis.We have generated an extensive genome-wide expression database from children with septic shock by way of microarray technology and have now leveraged this database to identify candidate biomarkers for SSAKI [27-32]. Herein we report the identification of 21 unique gene probes upregulated in patients with SSAKI, within the first 24 hours of admission to the pediatric intensive care unit (PICU), and their ability to robustly predict SSAKI.

Two readily measurable gene products from this list, matrix metalloproteinase-8 (MMP-8) and neutrophil elastase-2, show high sensitivity for SSAKI in a cohort of patients with septic shock.Materials and methodsPatients and data collectionThe study protocol was approved by the Institutional Review Boards of each participating institution (n = 11). Children ��10 years of age admitted to the PICU and meeting pediatric-specific criteria for septic shock were eligible for enrollment [33]. Controls, used to normalize the microarray data across the patients with septic shock and to conduct the three-group analysis of variance in the first derivation analysis, were recruited from the ambulatory departments of participating institutions using published inclusion and exclusion criteria [28-32]. These controls were required to reliably compare data across different batches of samples.

All patients and controls in the derivation cohort were previously reported in microarray-based studies addressing hypotheses entirely different from that of the current report [28-32]. All microarray data have been deposited in the NCBI Gene Expression Omnibus (GEO:”type”:”entrez-geo”,”attrs”:”text”:”GSE26440″,”term_id”:”26440″GSE26440 Brefeldin_A and GEO:”type”:”entrez-geo”,”attrs”:”text”:”GSE26378″,”term_id”:”26378″GSE26378). The patients in the validation cohort have not been previously reported in any manner.