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."
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!
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences