Navigation Links
Link between chronic kidney disease and oxygen-deprived tissue
Date:12/18/2007

PHILADELPHIA- 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. The findings appear in a December issue of the Journal of Clinical Investigation.

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 kidneys 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.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Comparison of obstetric outcomes between on-call and patients own obstetricians
2. Mailman School of Public Health study examines link between racial discrimination and substance use
3. New link between estrogen and breast cancer
4. Link Uncovered Between Benign Prostatic Hyperplasia and NSAIDs, Says Harvard Mens Health Watch
5. Link Between Chronic Pain and Insomnia Uncovered at PAINWeek 2007
6. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
7. Researchers discover correlation between GERD and obesity in females
8. NIH awards $10.8M to Columbia to study connection between diabetes and heart disease
9. Researchers Pinpoint Link Between Caloric Restriction and Longevity
10. Link Between Air Pollution, Stroke Gets Clearer
11. No Link Between Anti-Nausea Drug, Heart Trouble
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/27/2016)... (PRWEB) , ... May 27, 2016 , ... ... this installment is bolstered by inspiring human interest stories, courtesy of leaders in ... trends and tech within the industry, from leading advocates and associations—namely Jones & ...
(Date:5/26/2016)... ... May 26, 2016 , ... Despite last week’s media reports ... Yellen and company to wait until March 2017 for an interest rate increase, according ... Robinson College of Business. , “The Federal Open Market Committee (FOMC) dot charts are ...
(Date:5/26/2016)... ... May 26, 2016 , ... Intalere, the healthcare ... suppliers for its inaugural Member Conference at the Paris Hotel in Las Vegas, ... operational health of America’s healthcare providers. , The conference was highlighted by the ...
(Date:5/26/2016)... ... ... The Woodlands at John Knox Village , Florida’s first Life Plan ... and healing, celebrated its grand opening, today. The Woodlands at John Knox Village is ... Staff. , “This is an incredibly fulfilling time for John Knox Village as we ...
(Date:5/26/2016)... ... May 26, 2016 , ... ... solutions for drugs, biologics, consumer health and global clinical supply services, today announced ... to support the company’s continued investment and strategic growth plans in the Asia ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... , May 24, 2016  Joe Marziani has joined VMS BioMarketing as senior ... executive officer, today. In his new role, Marziani will lead the company,s business development ... professionals to improve outcomes. Photo - http://photos.prnewswire.com/prnh/20160523/371089 ... ... ...
(Date:5/24/2016)... KONG , May 24, 2016 ... stent de doble terapia del mundo, introduce catéteres ... arteriovenosa. OrbusNeich, una compañía global especializada ... las vidas, ha expandido su cartera incluyendo productos ... balón JADE™ y Scoreflex™ PTA son los dispositivos ...
(Date:5/24/2016)... -- Open Access Journal Focusing on ... Elsevier , a world-leading provider of scientific, technical ... launch of Clinical Neurophysiology Practice ... clinical practice issues in clinical neurophysiology. The journal will ... and didactic reviews. It is an official journal of ...
Breaking Medicine Technology: