[1668] Pathology of Kidney Injury in Septic Patients

Joseph P Gaut, Osamu Takasu, Paul E Swanson, Richard S Hotchkiss. Washington University School of Medicine, St. Louis, MO; University of Washington, Seattle, WA

Background: Acute kidney injury (AKI), defined clinically as a rapid increase in serum creatinine, complicates 30-60% of patients with sepsis. Such patients require intensive care, but mortality is unacceptably high (70%). The mechanistic basis for renal dysfunction in sepsis is poorly understood. There is currently an urgent need for standardizing diagnostic AKI criteria particularly for new AKI targeting therapies. Renal biopsy is rarely performed for septic AKI and therefore there is little pathologic data from humans. It is the aim of this study to evaluate the renal histopathology of septic AKI.
Design: Rapid postmortem kidney tissue harvest was performed at the bedside (n=26). Control specimens were retrospectively obtained from trauma and oncologic patients who underwent partial or total nephrectomy (n=21). Tissues were examined for apoptosis and necrosis by light microscopy and by immunohistochemical staining for KIM-1, active caspase-3, cytokeratin-18, and cleaved PARP. Acute tubular injury (ATI) and KIM-1 staining were quantified as the percentage of injured tubules per 200 tubular cross-sections.
Results: Light microscopy showed relatively mild alterations in septic kidneys. Tubular dilatation, epithelial flattening, and rare necrosis was seen in the renal cortex of 77% of septic cases, affecting an average of 6±1.2% of cortico-medullary junction (CMJ) tubules, and 1.2±0.4% of cortical tubules. In contrast to the mild light microscopic findings, KIM-1 was more sensitive for detecting ATI, highlighting 22% of the CMJ tubules and 12% of the cortical tubules, on average. Active caspase-3, cytokeratin-18, and cleaved PARP showed only rare staining. Interestingly, the medulla showed more frequent tubular necrosis in septic kidneys, affecting all septic patients, with an average of 22±2.4% of tubules injured. The remaining histologic findings were minimal.
Conclusions: These results support the hypothesis that ATI plays a role in the pathophysiology of septic kidney injury, but the pathologic findings are subtle. The CMJ and medulla are particularly susceptible to injury compared with the cortex. KIM-1 facilitates the diagnosis and may be a useful marker for standardizing the histopathologic criteria for ATI. Apoptosis does not appear to be a major mechanism of cell death in septic AKI. This investigation of lethal septic AKI in humans 1 hour after death provides unique insights into the underlying mechanism of septic renal dysfunction in humans.
Category: Kidney (does not include tumors)

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 275, Wednesday Afternoon


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