Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Keep the baby, toss the bathwater: How kidneys retain proteins, discard waste

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.

Michael C. Purdy | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital

nachricht Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>