Eurek Alert: Using a manmade version of a human antibody to directly deliver a drug that inhibits a powerful driver of inflammation, can reverse a disease course that often leads to kidney failure and dialysis, investigators report.
They have additionally found that it’s the powerhouses of kidney cells, called mitochondria, that are particularly impacted by the acute or chronic inflammation called nephritis, and that, at least in their animal model and cell cultures, the treatment restores their function.
Things like a serious infection or injury, and diseases like uncontrolled hypertension and diabetes, can cause acute or chronic ‘both kidneys and the million filtering units in each. Particularly when it’s chronic, patients often wind up in kidney failure on dialysis.”That is why we are looking at promoting recovery,” says Dr. Michael P. Madaio, nephrologist and chair of the Department of Medicine at the Medical College of Georgia at Augusta University.For their studies, they used a model of immune-mediated nephritis in mice that develops rapidly and progressively over seven to 10 days.But a few days after the disease was established, when they also gave a single dose of the protein kinase C-alpha inhibitor – delivered directly to the kidney via their manmade antibody – those mice instead recovered kidney function and survived.
Parallel studies that enabled the investigators to look directly at the impact of both toxicity and treatment on the endothelial cells that line the filtering units, also showed the inhibitor reduced cell death and improved cell recovery.A proteomic analysis determined that 157 proteins were significantly altered by nephritis – either up- or down-regulated by disease and restored by treatment – and that it was the mitochondria, the cell powerhouses, most affected.
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