Featured Research

from universities, journals, and other organizations

Keep The Baby, Toss The Bathwater: How Kidneys Retain Proteins, Discard Waste

Date:
August 2, 2006
Source:
Washington University School of Medicine
Summary:
New research may finally settle a decades-old debate about how the kidney keeps valuable blood proteins from harmfully slipping into the urine, a serious health symptom that often precedes kidney failure. In genetically modified mice, scientists at Washington University School of Medicine in St. Louis captured images of a defective version of a kidney structure, the glomerular basement membrane, leaking a substance from the blood into the urine.

New research may finally settle a decades-old debate about how the kidney keeps valuable blood proteins from harmfully slipping into the urine, a serious health symptom that often precedes kidney failure.

In genetically modified mice, scientists at Washington University School of Medicine in St. Louis captured images of a defective version of a kidney structure leaking a substance from the blood into the urine. The images suggest that the structure, known as the glomerular basement membrane (GBM), normally plays a key role in keeping blood proteins out of the urine.

The finding, reported in the August issue of the Journal of Clinical Investigation, will help doctors understand nephrotic syndrome, a condition with symptoms that include blood proteins in the urine. The syndrome can be triggered by a variety of genetic and environmental factors and leads to kidney failure over a varying time period.

"All the treatments we now use for nephrotic syndrome are either non-specific, meaning that we can't say for sure that they directly address the problem, or they are toxic," notes lead author George Jarad, M.D., a postdoctoral research scholar. "The first step to developing a specific treatment is to understand exactly what's happening. We have to know the details of the process before we can devise a remedy."

The new results are a reversal for nephrologists, who until a decade ago had long suspected the GBM was the primary barrier that retained blood plasma proteins. In the late 1990s, though, a Finnish research team bumped another structure, the slit diaphragm, into the position of prime suspect. They showed that a mutation in one of the proteins that make up the slit diaphragm caused a form of kidney disease that led to protein in the urine.

Both the slit diaphragm and the GBM are found in the glomeruli, small structures within the kidney that filter wastes from the blood and release them into the urine. Normally a small amount of blood protein leaks into the urine via this process and can be resorbed by the kidneys; however, when protein leakage levels go too high, scientists suspect this triggers a series of chain reactions that lead to kidney failure.

For their study, Jarad and colleagues in the labs of Jeffrey Miner, Ph.D., associate professor of medicine and cell biology and physiology, worked with mice lacking the gene for laminin beta 2, a protein that is part of the GBM. Two years ago, scientists linked a human mutation in the gene for laminin beta 2 to an inherited disorder that causes kidney disease and abnormalities in the eye and the neuromuscular system.

Scientists gave the mice ferritin, a protein often used as an imaging agent because it is easily detected by electron microscopes. They then used an electron microscope to take pictures of ferritin in the kidney and found it slipped more readily through the GBM in the genetically modified mice than it did in normal mice.

How comparable is ferritin to the blood proteins nephrologists are concerned about?

"Ferritin is actually much bigger than most blood proteins," Miner notes, "but other scientists have previously shown that, like blood proteins, ferritin is normally retained by the kidney."

Miner suspects--but cannot yet prove--that the problems in the slit diaphragm detected by the Finnish team may slow the ability of water to pass through the diaphragm and into the urine without affecting the passage of blood proteins. This could increase the concentration of protein passed into the urine without increasing the actual quantity of protein passed.

"It may be that the GBM is what determines the absolute amount of protein that's able to cross over into the urine, and the slit diaphragm and related structures determine its concentration," he explains. "It's a very complicated combination of fluid dynamics and physiology that we're still sorting out."

Miner and others are now working to determine how leakage of blood proteins through the GBM may lead to damage in structures beyond the membrane, potentially initiating a series of chain reactions that lead to kidney failure. They are also hoping to learn more about the kidneys' capabilities for resorption of proteins that have leaked into the urine.

Reference: Jarad G, Cunningham J, Shaw AS, Miner JH. Proteinurea precedes podocyte abnormalities in Lamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. The Journal of Clinical Investigation, August 2006.

Funding from the American Heart Association and the National Institutes of Health supported this research.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School of Medicine. "Keep The Baby, Toss The Bathwater: How Kidneys Retain Proteins, Discard Waste." ScienceDaily. ScienceDaily, 2 August 2006. <www.sciencedaily.com/releases/2006/08/060802103022.htm>.
Washington University School of Medicine. (2006, August 2). Keep The Baby, Toss The Bathwater: How Kidneys Retain Proteins, Discard Waste. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2006/08/060802103022.htm
Washington University School of Medicine. "Keep The Baby, Toss The Bathwater: How Kidneys Retain Proteins, Discard Waste." ScienceDaily. www.sciencedaily.com/releases/2006/08/060802103022.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins