Featured Research

from universities, journals, and other organizations

Chronic Kidney Disease Linked To Oxygen-deprived Tissue

Date:
December 20, 2007
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers have discovered how low-oxygen conditions can worsen chronic kidney disease. The key player is a protein called hypoxia-inducible-factor that, as its name suggests, is active when the kidney does not get enough oxygen, a condition known as hypoxia. This research has implications for new approaches to kidney dialysis.

Researchers at the University of Pennsylvania School of Medicine have discovered how low-oxygen conditions can worsen chronic kidney disease (CKD). The key player is a protein called hypoxia-inducible-factor (HIF-1) that, as its name suggests, is active when the kidney does not get enough oxygen, a condition known as hypoxia.

Related Articles


CKD afflicts 20 million Americans who have hypertension, atherosclerosis, diabetes, and other conditions. The kidney has less oxygen reserves than other organs to start, and CKD is associated with less capillary blood flow, reducing oxygenation even further. As CKD progresses, kidneys become full of fibrous tissue and cannot filter wastes out of blood or regulate body salt. Eventually kidney dialysis, a form of renal replacement therapy, may be needed to carry out these processes. Ultimately, the clinical goal is to optimize treatment to halt or delay the progression of CKD by better understanding its molecular underpinnings.

"Fibrosis worsens when the kidney becomes hypoxic," states lead author Volker Haase, MD, Assistant Professor of Medicine, Renal Electrolyte and Hypertension Division. "We found that HIF-1 is more stable when oxygen is in short supply and that HIF-1 causes kidney epithelial cells to regress to a less-differentiated cell type. This transition is driven by HIF-1, a protein that turns on many genes that promote the synthesis of fibrous connective tissue, thus interfering with the kidney's normal filtering function," says Haase.

The study was conducted using mice that had been engineered to turn off expression of HIF-1 (a critical subunit of HIF-1) in their kidneys. One kidney from each mouse was put under oxygen stress by obstructing the ureter, and the other kidney served as a control. As long as HIF-1a was silenced, fibrosis was reduced in the oxygen-deprived kidney. This demonstrated that HIF-1 promoted the fibrotic process under reduced oxygen conditions.

Kidney biopsies from patients with diabetes who also suffer from CKD were tested for HIF-1 levels. Normal kidneys had almost no HIF-1, whereas kidneys from diabetics had moderate to high expression of HIF-1. "This observation, along with increased expression of the genes controlled by HIF-1 in diseased kidneys in mice, shows that HIF-1 is the molecular link between hypoxia and CKD in humans as well as rodents," says Haase.

The next step is to test other models of CKD and identify additional molecular targets of HIF-1 that can promote fibrosis. "We also hope to study the inflammatory response to hypoxia in the diseased kidney," concludes Haase. "We already know that some pro-inflammatory proteins are stimulated by hypoxia."

Some day, it may be possible to use HIF-1 and HIF-regulated genes as molecular markers to identify those patients that are at high risk for rapid progression of CKD requiring dialysis.

The findings appear in a December issue of the Journal of Clinical Investigation. This study was carried out by D. F. Higgins PhD, N. Shrimanker BA and Y. Akai, MD- PhD of the University of Pennsylvania; K. Kimura MD, Y. Akai MD, Y. Saito MD and M. Iwano MD of Nara Medical University, Japan; W. M. Bernhardt MD, B. Hohenstein MD and K-U. Eckardt MD of Friedrich-Alexander University, Germany; R. S. Johnson PhD of UCSD; M. Kretzler MD of University of Michigan; and C. D. Cohen MD of University of Munich, Germany. This research was supported by the National Institutes of Health, the University of Pennsylvania Research Foundation, the Penn Center for Molecular Studies in Digestive and Liver Disease, the Ministry of Education and Science of Japan, the American Heart Association and the Deutsche Forschungsgemeinschaft.


Story Source:

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


Cite This Page:

University of Pennsylvania School of Medicine. "Chronic Kidney Disease Linked To Oxygen-deprived Tissue." ScienceDaily. ScienceDaily, 20 December 2007. <www.sciencedaily.com/releases/2007/12/071218105414.htm>.
University of Pennsylvania School of Medicine. (2007, December 20). Chronic Kidney Disease Linked To Oxygen-deprived Tissue. ScienceDaily. Retrieved November 21, 2014 from www.sciencedaily.com/releases/2007/12/071218105414.htm
University of Pennsylvania School of Medicine. "Chronic Kidney Disease Linked To Oxygen-deprived Tissue." ScienceDaily. www.sciencedaily.com/releases/2007/12/071218105414.htm (accessed November 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN Says It Will Scale Up Its Ebola Response

UN Says It Will Scale Up Its Ebola Response

AFP (Nov. 20, 2014) UN Resident Coordinator David McLachlan-Karr and WHO representative in the country Daniel Kertesz updated the media on the UN Ebola response on Wednesday. Duration: 00:51 Video provided by AFP
Powered by NewsLook.com
Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Reuters - US Online Video (Nov. 20, 2014) U.S. Congress hears from a victim and company officials as it holds a hearing on the safety of Takata airbags after reports of injuries. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Obesity Costs Almost As Much As War And Terrorism

Obesity Costs Almost As Much As War And Terrorism

Newsy (Nov. 20, 2014) The newest estimate of the cost of obesity is pretty jarring — $2 trillion. But how did researchers get to that number? Video provided by Newsy
Powered by NewsLook.com
Calling All Men: Here's Your Chance to Experience Labor Pains

Calling All Men: Here's Your Chance to Experience Labor Pains

Reuters - Light News Video Online (Nov. 20, 2014) Chinese hospital offers men a chance to experience the pain of child birth via electric shocks. Sharon Reich reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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