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Systemic inflammatory response syndrome (SIRS) is characterized by the activation of the innate immune system resulting in stimulation of inflammatory responses, coagulation, and platelet activation that may contribute to complication such as the development of acute kidney injury (AKI). AKI importantly worsens the outcome of SIRS, implying the existence of a detrimental cross talk via systemic messages. Mitochondria are a source of damage-associated molecular patterns (DAMPs) and are thought to form a molecular link between tissue injury and stimulation of innate immunity. The role of mitochondrial DNA (mtDNA) in the cross talk between the onset of SIRS and subsequent development of AKI is unknown. Hence, we performed a case control study in critically ill patients with SIRS diagnosed with or without AKI, in which we determined mtDNA levels in plasma and urine, and correlated these to markers of renal impairment, inflammation, coagulation, and platelet activation. In addition, we exposed mice, primary renal tubular epithelial cells (TECs), and platelets to mtDNA or purified mitochondrial ligands, and measured their response to elucidate underlying pathophysiological mechanisms. Our data reveal that increased systemic mtDNA levels in SIRS patients do not correlate with systemic inflammation and renal disease activity. Moreover, AKI does not have an additional effect on circulating mtDNA levels. In contrast, we found that urinary mtDNA levels correlate with an elevated albumin creatinine ratio (ACR) as well as with increased urinary markers of inflammation, coagulation, and platelet activation. Both renal TECs and platelets respond to mtDNA and mtDNA ligands, leading to increased expression of, respectively, inflammatory cytokines and P-selectin. Moreover, activation of platelets results in mtDNA release. Together, these data suggest that circulating mtDNA is probably not important in the detrimental cross talk between SIRS and AKI, whereas renal mtDNA accumulation may be related to intrarenal inflammation, coagulation processes, and renal dysfunction in the pathophysiology of SIRS.

Objective: To evaluate the prognostic significance of microalbuminuria in critically ill children., Design: Prospective study., Setting: PICU of a teaching hospital., Patients: Admitted critically ill children., Interventions: The urine albumin-creatinine ratio was measured at admission and at 24 hours. Pediatric Risk of Mortality, Pediatric Index of Mortality II, Pediatric Logistic Organ Dysfunction, and Inotrope Score were calculated., Measurements and Main Results: In total, 102 patients (median age, 19 mo) were included in the study, among whom were 30 mortalities. Microalbuminuria was identified in 62 patients (64%). The patients were classified into three groups: patients with sepsis, patients with noninfectious systemic inflammatory response syndrome, and patients without systemic inflammatory response syndrome. The highest clinical scores, albumin-creatinine ratio levels, mortality rate, and duration of mechanical ventilation were found in the sepsis group, and the lowest values were seen in patients without systemic inflammatory response syndrome (p < 0.05). Significant correlations were observed between the albumin-creatinine ratio levels and the clinical scores (p < 0.05). The receiver operating characteristics curve analysis showed that the areas under the curves were 0.818 and 0.781, respectively, for albumin-creatinine ratio measured at admission and at 24 hours to identify PICU mortality. At a cutoff value of 34.2 mg/g, albumin-creatinine ratio measured at admission may be able to discriminate between patients a with sensitivity of 63.3%, specificity of 93.3%, positive predictive value of 95%, and negative predictive value of 56%., Conclusions: Microalbuminuria is a simple, inexpensive, and useful tool for predicting mortality and morbidity in critically ill children in the PICU.

Background: Intestinal mucosal ischemia and subsequent barrier dysfunction have been related to the development of organ dysfunction and death in the critically ill. We hypothesized that urine concentrations of intestinal fatty acid binding protein (IFABP), a sensitive marker of intestinal ischemia, might predict the development of the systemic inflammatory response syndrome (SIRS) and organ dysfunction., Methods: One hundred consecutive critically ill patients were prospectively studied for the development of infectious complications, organ dysfunction, and SIRS. Urine was collected daily for measurement of IFABP., Results: A total of 58 males and 42 females (mean age, 56 years; range,16-85 years) were studied. Of these 100 patients, 40 patients developed complications and 5 patients developed SIRS. IFABP was significantly elevated in all patients with SIRS, and IFABP levels peaked an average of 1.4 days (range, 0-7 days) before the diagnosis of SIRS., Conclusion: Elevated concentrations of urine IFABP correlated with the clinical development of SIRS. Studies to assess the utility of IFABP as a predictor of organ dysfunction and SIRS in the critically ill are warranted.