New biological mechanisms, treatment paradigm for kidney disease

New biological mechanisms, treatment paradigm for kidney disease

Prevention and reversal of chronic kidney disease is an urgent public health need. The disease affects 1 in 10 Americans, is debilitating and deadly, and existing drugs, at best, offer only mild delay in progression to end-stage kidney failure. New research has uncovered abnormal molecular signaling pathways from disease initiation to irreversible kidney damage, kidney failure, and death.

via Top Health News — ScienceDaily:

Prevention and reversal of chronic kidney disease is an urgent public health need. The disease affects 1 in 10 Americans, is debilitating and deadly, and existing drugs, at best, offer only mild delay in progression to end-stage kidney failure. New research led by Icahn School of Medicine at Mount Sinai investigators has uncovered abnormal molecular signaling pathways from disease initiation to irreversible kidney damage, kidney failure, and death. Results from their preclinical and human research are published online March 3 in the Journal of Clinical Investigation.“Our group is the first to show that endothelial mitochondrial oxidative stress [damage to blood vessel lining that affects the energy-producing part of the cell caused by oxidative stress] regulates the passage of proteins from blood to urine and filtration of waste products in the kidney,” said Erwin Bottinger, MD, Director of the Charles Bronfman Institute for Personalized Medicine, and the study’s senior author. Specifically, the researchers found albuminuria (protein in the urine) and depletion of the cells that form the kidney’s glomerular filtration barrier. “These findings were unexpected and open the door for developing new therapeutic targets,” Dr. Bottinger added.In the preclinical part of the research, investigators used a mouse model to induce scarring in the filtration part of the kidney, or glomeruli. This allowed progressive amounts of protein to pass into the urine and interfered with the clearance of waste products by the kidney. Essentially, the researchers were examining how different signaling mechanism and cellular interactions work, and how when they are disturbed, they promote chronic kidney disease.Initially, key cells of the glomerular filtration barrier, also called podocytes, cause alterations in endothelin-1, a vasoconstrictor, activating the endothelin receptor A. The activated endothelin receptor A triggered disturbances manifested as endothelial mitochondrial oxidative stress.The research team was able to confirm that this worked the same way in humans. …

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Top Health News — ScienceDaily

New biological mechanisms, treatment paradigm for kidney disease

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