Navigation Links
Protein offers new clue to cause and treatment for kidney disease
Date:12/12/2010

BIRMINGHAM, Ala. 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."


'/>"/>

Contact: Jennifer Park Lollar
jpark@uab.edu
205-934-3888
University of Alabama at Birmingham
Source:Eurekalert

Related medicine news :

1. New and Delicious, Almond Butter Filled, Cookie Bites With 35.7% Protein to Help Manage Weight and Build Muscle
2. Research highlights role of protein pair in obesity regulation
3. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
4. Smithfield, United Food and Commercial Workers Union, and Food Networks Paula Deen to Deliver 150,000 Servings of Protein to San Francisco Food Bank
5. Protein Sciences Corporation Announces Profitable and Cash Flow Positive Results for 2009 and Management Realignment
6. Protein Appears Key to Intestinal Balance
7. SIBLING proteins may predict oral cancer
8. Damaged protein identified as early diagnostic biomarker for Alzheimers disease in healthy adults
9. Cells of aggressive leukemia hijack normal protein to grow
10. Omega Protein Comments on California Lawsuit Alleging Fish Oil Contaminants
11. Proteins May Predict Spread of Colon Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... ... working together to expand dental health services to the developmentally disabled in the ... Care Dental’s operations to a new facility at 71-949 Highway 111, Suite 100-B, ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... ... tracking solution, The Guard, to associations of medical professionals throughout the country. The ... including security risk assessments, policies and procedures, employee training, regulatory updates, and compliance ...
(Date:2/10/2016)... ... ... Dr. Jessica Barron, of Barron Family Dental in Thornton, Colorado , is ... the North Metro Denver area. The new dental practice focuses on comfort where patients ... the most relaxing environment. , While some dental visits can create anxiety for patients, ...
(Date:2/10/2016)... ... ... AxoGen, Inc. (NASDAQ: AXGN), a leading medical technology company focused on the peripheral ... December 31, 2015 on Monday, February 29, 2016 after the market closes. , The ... release at 4:30 PM ET. Investors interested in participating by phone are invited to ...
(Date:2/10/2016)... MN (PRWEB) , ... February 10, 2016 , ... ... that it will attend the Ohio Safety Congress and Expo event March 9-11, ... at the Greater Columbus Convention Center. , As the longest running and ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... 2016 CERS ), Medivation, Inc. (NASDAQ: ... and Celldex Therapeutics, Inc. (NASDAQ: CLDX ). --> ... Pharmaceuticals, Inc. (NASDAQ: ADMS ) and Celldex Therapeutics, Inc. ... Drug Designations become vitally important in the development of targeted ... and biologics which are defined as those intended for the ...
(Date:2/10/2016)... 2016 ALSP, Inc. announced that it has appointed ... Medical Affairs in preparation for its move into clinical trials ... CEO, stated, "We are pleased to welcome Dallas Hack ... with an individual of such practical knowledge and far-reaching experience ... deeply on his broad experience and success as a clinician ...
(Date:2/10/2016)... 9, 2016 On Tuesday, February ... met with its Arthritis Advisory Committee to ... Johnson & Johnson,s Remicade and most likely ... the U.S. The Biologics Prescribers Collaborative (BPC) ... Alliance for Patient Access, American Association of ...
Breaking Medicine Technology: