Subtypes and Mimics of Sepsis.

Sepsis is a heterogenous and imprecise syndrome that includes multiple phenotypes, some of which are amenable to specific therapies. Developing new therapies for sepsis will require focusing on subsets of patients. Key to improving care is evaluating patients for sepsis mimics and treatable diseases whose manifestations lead to a clinical classification of sepsis. Because sepsis is common, it is easy to overlook unusual causes of organ failure and succumb to confirmation bias about the nature of an illness. Careful attention to medical and family histories, focused diagnostic testing, and subspecialty input can help identify potentially treatable diseases masquerading as typical sepsis.

Uncommon Causes of Acute Kidney Injury.

Acute kidney injury (AKI) is one of the most important complications of critical illness and a significant public health concern. AKI is commonly associated with sepsis, cardiac dysfunction, and exposure to nephrotoxic medication; however, less common causes of AKI can lead to devastating patient outcomes when the underlying diagnosis is missed or delayed. These uncommon causes of AKI fall into 3 large categories: structural, immune mediated, and microvascular, including various types of thrombotic microangiopathy. Kidney imaging, urine studies, and serum hemolytic studies should be a routine part of the evaluation of AKI among critically ill patients.

Association of early hyponatremia and the development of acute kidney injury in critically ill children.

BACKGROUND: Hyponatremia is an independent prognostic factor for mortality; however, the reason for this remains unclear. An observed relationship between hyponatremia and the development of acute kidney injury (AKI) has been reported in certain disease states, but hyponatremia has not been evaluated as a predictor of AKI in critically ill patients or children. METHODS: This is a single-center retrospective cohort study of critically ill children admitted to a tertiary care center. We performed regression analysis to assess the association between hyponatremia at ICU admission and the development of new or worsening stage 2 or 3 (severe) AKI on days 2-3 following ICU admission. RESULTS: Among the 5057 children included in the study, early hyponatremia was present in 13.3% of children. Severe AKI occurred in 9.2% of children with hyponatremia compared to 4.5% of children with normonatremia. Following covariate adjustment, hyponatremia at ICU admission was associated with a 75% increase in the odds of developing severe AKI when compared to critically ill children with normonatremia (aOR 1.75, 95% CI 1.28-2.39). Evaluating sodium levels continuously, for every 1 mEq/L decrease in serum sodium level, there was a 0.05% increase in the odds of developing severe AKI (aOR 1.05, 95% CI 1.02-1.08). Hyponatremic children who developed severe AKI had a higher frequency of kidney replacement therapy, AKI or acute kidney disease at hospital discharge, and hospital mortality when compared to those without. CONCLUSIONS: Hyponatremia at ICU admission is associated with the development of new or worsening AKI in critically ill children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association of Acute Kidney Injury With Subsequent Sepsis in Critically Ill Children.

OBJECTIVES: Acute kidney injury is a major cause of morbidity and mortality in critically ill children. A growing body of evidence has shown that acute kidney injury affects immune function, yet little is known about the association between acute kidney injury and subsequent infection in pediatric patients. Our objective was to examine the association of non-septic acute kidney injury with the development of subsequent sepsis in critically ill children. DESIGN: A single-center retrospective cohort study. SETTING: The pediatric and cardiac ICUs at a tertiary pediatric care center. PATIENTS: All patients 0-18 years old without a history of chronic kidney disease, who did not have sepsis prior to or within the initial 48 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data for 5,538 children (median age, 5.3 yr; 58.2% male), and identified 255 (4.6%) with stage 2 or 3 acute kidney injury. Suspected sepsis occurred in 46 children (18%) with stage 2 or 3 acute kidney injury compared to 286 children (5.4%) with stage 1 or no acute kidney injury. On adjusted analysis, children with stage 2 or 3 acute kidney injury had 2.05 times greater odds of developing sepsis compared to those with stage 1 or no acute kidney injury (95% CI, 1.39-3.03; p < 0.001). Looking at acute kidney injury severity, children with stage 2 and 3 acute kidney injury had a 1.79-fold (95% CI, 1.15-2.79; p = 0.01) and 3.24-fold (95% CI, 1.55-6.80; p = 0.002) increased odds of developing suspected sepsis, respectively. CONCLUSIONS: Acute kidney injury is associated with an increased risk for subsequent infection in critically ill children. These results further support the concept of acute kidney injury as a clinically relevant immunocompromised state.

Kidney-Immune System Crosstalk in AKI.

Acute kidney injury (AKI) now is recognized as a systemic disease. It occurs frequently in critically ill patients and has profound effects on morbidity and mortality. Recent research efforts have shown a bidirectional interplay between AKI and the immune system. Both innate and adaptive immune responses mediate renal injury as well as recovery from AKI. Dendritic cells, monocytes/macrophages, neutrophils, T lymphocytes, and B lymphocytes all play specific roles in the development of AKI. M2 macrophages and regulatory T cells also are pivotal in controlling inflammation, tissue remodeling, and repair after AKI. Conversely, existing evidence also suggests that increased production and decreased clearance of cytokines as well as dysfunction of immune cells, in particular neutrophils, can contribute to immune dysfunction and impaired bacterial clearance during AKI. Clinical data indicate that AKI is a risk factor for infections after various forms of critical illness, including cardiac surgery, malignancies, or severe trauma. Available evidence does not suggest that standard renal replacement therapies improve outcome from AKI beyond control of fluid balance and azotemia. Thus, novel approaches likely will be necessary to prevent or treat AKI-induced dysregulation of the inflammatory response.