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!
Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University
Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
22.08.2017 | Health and Medicine
22.08.2017 | Materials Sciences
22.08.2017 | Life Sciences