Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breakdown of kidney's ability to clean its own filters likely causes disease

31.01.2008
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.

A protein known as FcRn was high on the list of likely suspects. Akilesh had studied FcRn previously in the laboratory of coauthor Derry C. Roopenian, Ph.D., professor at the Jackson Laboratory in Bar Harbor, Maine. Prior research there and in other laboratories had revealed that FcRn binds to both IgG and albumin and is present in human podocytes.

After confirming that the FcRn protein also is made in mouse podocytes, scientists then asked if FcRn was responsible for clearing IgG antibody from the filter. To do this, they measured the retention of a radioactive tracer in the kidneys of normal mice and in mice where the gene for FcRn had been disabled. Mice lacking FcRn had difficulty clearing antibody from the kidney.

When researchers studied the mice lacking FcRn for longer periods of time, they saw evidence that antibodies were accumulating in the kidney.

In another experiment, researchers gave the mice injections of large quantities of protein to saturate the clearance system. They followed those injections with what would normally have been a harmlessly small dose of an antibody potentially toxic to the kidney. The mice developed kidney damage as a result. Researchers believe this was because they couldn't clear the toxic antibody from the GBM quickly enough.

"This is the first clear demonstration that the filter system in the kidney isn't just a passive mechanical filter, it's actually involved in its own maintenance," says Akilesh. "It also provides us with a nice mechanism for explaining how the normal function of this filter may be breaking down in ways that leads to kidney disease and damage."

To follow up, Shaw plans to look for other podocyte proteins involved in filter clearance.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>