Cause of cancer-associated kidney injury identified
A new study, carried out by investigators from Uppsala University and Dalarna University in Sweden, uncovers the mechanism by which a tumor contributes to kidney dysfunction and provides a potential approach to prevent kidney dysfunction in cancer patients.
Renal insufficiency, or called kidney failure, is poor condition of the kidneys that may result from a decrease in blood flow to the kidneys. Renal insufficiency is a common complication of cancer: it affects more than half of all cancer patients and is strongly correlated with poor patient outcomes. Until now, the molecular mechanism of how a tumor drives kidney dysfunction remains unknown, impeding the development of treatments.
Lead researcher of this study, Anna-Karin Olsson, and colleagues set out to elucidate the pathogenesis of cancer-induced renal insufficiency. In previous research, Olsson found that neutrophils, a type of white blood cells that fight infections, form a structure called neutrophil extracellular traps (NETs) in the vasculature of mice with cancer. Formation of NETs is one of the strategies that neutrophils use to capture and kill pathogens. But tumors can stimulate the activation of neutrophils even in the absence of an infection, leading to tissue damage.
In their latest work, described in a paper in the journal Oncoimmunology, Olsson's team demonstrated that the formation of NETs is a cause of kidney injury in tumor-bearing mice. By analyzing clinical biomarkers for kidney function, the researchers found impaired creatinine clearance and elevated total protein levels in urine samples from tumor-bearing mice. With the help of electron microscopy, they observed reversible pathological signs such as mesangial hypercellularity in the animals' kidney. These signs of kidney injury are similar to those seen in cancer patients. When the researchers treated the mice with an inhibitor that targets PAD4 -- an enzyme essential for the formation of NETs, kidney function of the animals was restored.
Collectively, the study identifies the formation of NETs as a cause of cancer-associated kidney dysfunction and points to a potential approach to prevent it.
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