Low dose of endotoxin could have protective effect on men at risk of acute kidney injury

In a counterintuitive result, researchers found that giving male rats a low dose of the endotoxin lipopolysaccharide (LPS) prior to inducing a model of acute kidney injury (AKI) improved outcomes. Their study will be presented today at the 2019 American Physiological Society (APS)/American Society of Nephrology (ASN) Conference, Control of Renal Function in Health and Disease in Charlottesville, Va.

AKI is a loss of kidney function that occurs within a few hours or days. It is a common and growing in-hospital complication, occurring in 1 in 5 patients. According to the U.S. Centers for Disease Control and Prevention, it is associated with high hospital mortality, increased health care costs, need for long-term care and risk of chronic kidney disease. Diabetes is a risk factor for AKI. As the number of people diabetes with continues to increase, rates of AKI are expected to grow as well.

LPS is a toxic compound found in the cell membrane of some types of bacteria, including Escherichia coli (E. coli) and salmonella. It can be a factor in the development of septic shock. In a research setting, LPS is used to trigger and then study innate immune responses and inflammation.

In this study, researchers administered either saline or low-dose LPS to cohorts of male and female rats daily for seven days. After seven days, they induced a model of restricted blood supply-induced AKI. They then examined the blood and tissue for markers related to inflammation, kidney injury and red blood cell congestion in the innermost part of the kidney, a hallmark of this type of AKI.

Males showed a dose-dependent increase in a measure of inflammation called the erythrocyte sedimentation rate. Females, however, showed no difference from the saline control group. Males that received the low-dose LPS showed less red blood cell congestion than other groups despite increased inflammation. All female groups resembled their control.

We are excited about the outcomes of this study and its potential in delineating the potential role of renal vascular congestion to drive long-term complications following restricted blood-supply AKI."

Lead author Sarah Ray

The discovery of this protective effect may help determine the specific mechanisms at work and the development of a therapy for red blood cell congestion that does not cause the wide-scale inflammation triggered by LPS.

Sarah Ray of Augusta University in Georgia will present "Sex differences in pretreatment with low dose lipopolysaccharide on IR induced red blood cell congestion in the renal medulla" on Tuesday, June 25, 2019, at the Boar's Head Resort in Charlottesville, Va.