The kidney actively cleans its most selective filter to keep it from clogging with blood proteins, scientists from Washington University School of Medicine in St. Louis reveal in a new study.
Researchers showed that breakdown of this self-cleaning feature can make kidneys more vulnerable to dysfunction and disease.
"We speculate that defects of this clearance mechanism can leave things on the filter that can damage it," says senior author Andrey Shaw, M.D., Emil R. Unanue Professor of Immunobiology in Pathology and Immunology. "This could include autoimmune antibodies that mistakenly target the body's own tissues like those that occur in the disease lupus."
The study appears in the Jan. 22 Proceedings of the National Academy of Sciences.
Despite extensive knowledge of the structure of the kidney, several scientific controversies linger over how the organ does its complicated and essential job of filtering wastes from the blood for disposal without simultaneously discarding too much water or key blood proteins in the urine. Understanding how these tricky tasks are accomplished is essential to developing new treatments for kidney disease and renal failure, which are among the top ten causes of death in the United States.
Like many mechanical filtering systems, the kidney passes the blood through a series of progressively finer screens. After passing through a structure known as the glomerular basement membrane (GBM), fluid and serum proteins must finally pass through the most selective filter of the kidney, which is comprised of specialized epithelial cells called podocytes. These cells form a web-like barrier to the passage of large serum proteins into the urine.
"The kidney screens 150 to 200 liters of blood daily, and we were curious as to how the kidney keeps the filter from clogging up," says first author Shreeram Akilesh, an M.D./Ph.D. student. "The two most common blood serum and plasma proteins are albumin, which helps regulate blood volume and convey a number of different substances around the body, and immunoglobin G (IgG), a type of immune system antibody. Because they're so common, we figured they would be among the most likely to get stuck on the filter, and set out to look for proteins that help clear them."
Researchers looked for proteins made in podocytes that could bind to albumin and IgG, reasoning that such proteins likely provide the "handles" the podocytes need to grab proteins and clear them from the filter.