Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein offers new clue to cause and treatment for kidney disease

13.12.2010
University of Alabama at Birmingham researchers have pinpointed a protein that compromises the kidney's filtering ability, causing nephrotic syndrome, and demonstrated that a naturally occurring precursor of an acid in the body offers potential for treating some forms of the condition.

The research was published online Dec. 12 in Nature Medicine.

"This is a major breakthrough in understanding the development and treatment of kidney disease associated with proteinuria, the leakage of protein in the urine," said the study's lead author Sumant Singh Chugh, M.D., associate professor of medicine in the UAB Division of Nephrology.

Nephrotic syndrome is characterized by the presence of excessive protein in the urine, low blood-protein levels, high cholesterol, high triglycerides and swelling. Common causes include diabetic nephropathy, minimal change disease, focal and segmental glomerulosclerosis and membranous nephropathy. It also can be caused by infections, certain drugs, cancer, genetic disorders, immune disorders or diseases that affect multiple body systems including lupus, multiple myeloma and amyloidosis.

Chugh said his research team, studying transgenic rats, discovered that in some forms of nephrotic syndrome, a protein called Angiopoietin-like 4 is over-produced in specialized cells called podocytes. Podocytes are found in the glomerular filter, which cleans the blood to produce urine. As a result of the over-production, the efficiency of this filter is compromised, resulting in the loss of blood proteins in the urine. When this dysfunction is severe, it causes nephrotic syndrome.

Chugh said the researchers also determined that the Angiopoietin-like 4 protein lacks the attachment of adequate amounts of sialic acid, a modified carbohydrate that affects the protein's adhesive properties. By feeding sialic acid precursor ManNAc to transgenic rats that over-produce Angiopoietin-like 4 in podocytes, the researchers were able to increase the amount of protein-bound sialic acid, and reduce the amount of protein leakage into the urine by more than 40 percent.

"These findings, at present, most directly relate to minimal change disease, a form of nephrotic syndrome commonly seen in children, but are also likely to be relevant to common causes of proteinuria and nephrotic syndrome in adults, including those with diabetes," Chugh said.

He added that this study is important because traditional forms of therapy, which include the use of glucocorticoids, for example prednisone, and other immunosuppressive drugs can have significant toxicity, especially after prolonged use or repeated cycles of treatment. However, sialic acid and ManNAc are naturally occurring substances in the body, and toxicity is likely to be limited. The investigators, he said, believe that relatively small doses of the sialic acid may be effective for nephrotic syndrome, since, unlike most other cells in the body, the target cell in the kidney does not divide under most conditions and is likely to accumulate these compounds even at low doses.

"The major known toxicity of sialic acid therapy observed by other investigators in a mouse model of the human muscle disease, hereditary inclusion body myopathy, was the development of ovarian cysts at very high doses," Chugh said. "These doses are approximately 20-fold higher than those used to reduce proteinuria in rats in the current study; knowing that, we believe sialic acid repletion has potential in the future treatment of Minimal Change Disease and some other forms of nephrotic syndrome."

About UAB

Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham (UAB) is the state of Alabama's largest employer and an internationally renowned research university and academic health center whose professional schools and specialty patient care programs are consistently ranked as among the nation's top 50; find more information at www.uab.edu and www.uabmedicine.org.

EDITOR'S NOTE: The University of Alabama at Birmingham (UAB) is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on all consecutive references.

VIDEO: www.youtube.com/uabnews TEXT: www.uab.edu/news TWEETS: www.twitter.com/uabnews

Jennifer Park Lollar | EurekAlert!
Further information:
http://www.uab.edu

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>