Featured Research

from universities, journals, and other organizations

New biological mechanisms, treatment paradigm for kidney disease

Date:
March 3, 2014
Source:
Mount Sinai Medical Center
Summary:
Prevention and reversal of chronic kidney disease is an urgent public health need. The disease affects 1 in 10 Americans, is debilitating and deadly, and existing drugs, at best, offer only mild delay in progression to end-stage kidney failure. New research has uncovered abnormal molecular signaling pathways from disease initiation to irreversible kidney damage, kidney failure, and death.

Prevention and reversal of chronic kidney disease is an urgent public health need. The disease affects 1 in 10 Americans, is debilitating and deadly, and existing drugs, at best, offer only mild delay in progression to end-stage kidney failure. New research led by Icahn School of Medicine at Mount Sinai investigators has uncovered abnormal molecular signaling pathways from disease initiation to irreversible kidney damage, kidney failure, and death. Results from their preclinical and human research are published online March 3 in the Journal of Clinical Investigation.

Related Articles


“Our group is the first to show that endothelial mitochondrial oxidative stress [damage to blood vessel lining that affects the energy-producing part of the cell caused by oxidative stress] regulates the passage of proteins from blood to urine and filtration of waste products in the kidney,” said Erwin Bottinger, MD, Director of the Charles Bronfman Institute for Personalized Medicine, and the study’s senior author. Specifically, the researchers found albuminuria (protein in the urine) and depletion of the cells that form the kidney’s glomerular filtration barrier. “These findings were unexpected and open the door for developing new therapeutic targets,” Dr. Bottinger added.

In the preclinical part of the research, investigators used a mouse model to induce scarring in the filtration part of the kidney, or glomeruli. This allowed progressive amounts of protein to pass into the urine and interfered with the clearance of waste products by the kidney. Essentially, the researchers were examining how different signaling mechanism and cellular interactions work, and how when they are disturbed, they promote chronic kidney disease.

Initially, key cells of the glomerular filtration barrier, also called podocytes, cause alterations in endothelin-1, a vasoconstrictor, activating the endothelin receptor A. The activated endothelin receptor A triggered disturbances manifested as endothelial mitochondrial oxidative stress.

The research team was able to confirm that this worked the same way in humans. They studied kidney biopsies, comparing ten biopsies with glomerular sclerosis with six controls. Like in the animal models, the researchers confirmed activated endothelin receptor A and endothelial mitochondrial dysfunction in human glomerular sclerosis biopsies, but not in controls.

“These processes were absolutely essential in causing protein in the urine [or albuminuria], injured podocytes (tiny ball-shaped structures that constrict the blood vessels in the filtering part of the kidney), and cause scarring, all of which can ultimately lead to long-term, irreversible kidney disease. “This is called crosstalk and it is poorly understood,” said Ilse S. Daehn, PhD, the study’s lead researcher, and Assistant Professor of Medicine in the Division of Nephrology, at the Icahn School of Medicine at Mount Sinai. “We hope that these novel crosstalk findings lead to new therapies that help reverse or arrest chronic kidney disease, which affect millions of Americans,” added Dr. Daehn.

Antioxidants that target the mitochondria and endothelin antagonists would alter the paradigm for preventing cell depletion and scarring of the filtration part of the kidney. “There is a pressing unmet medical need to prevent or reverse chronic kidney disease,” Dr. Bottinger stressed. “The renin angiotensin inhibitors and angiotensin receptor blockers that are now widely used have not been proven effective in preventing end stage kidney failure. We need more effective drugs to treat the millions of Americans suffering from chronic kidney disease with the goal to eliminate its progression to end- stage kidney failure and with it the need for chronic dialysis and kidney transplantation.”


Story Source:

The above story is based on materials provided by Mount Sinai Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ilse Daehn, Gabriella Casalena, Taoran Zhang, Shaolin Shi, Franz Fenninger, Nicholas Barasch, Liping Yu, Vivette D’Agati, Detlef Schlondorff, Wilhelm Kriz, Borje Haraldsson, Erwin P. Bottinger. Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI71195

Cite This Page:

Mount Sinai Medical Center. "New biological mechanisms, treatment paradigm for kidney disease." ScienceDaily. ScienceDaily, 3 March 2014. <www.sciencedaily.com/releases/2014/03/140303153928.htm>.
Mount Sinai Medical Center. (2014, March 3). New biological mechanisms, treatment paradigm for kidney disease. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2014/03/140303153928.htm
Mount Sinai Medical Center. "New biological mechanisms, treatment paradigm for kidney disease." ScienceDaily. www.sciencedaily.com/releases/2014/03/140303153928.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Hugging It Out Could Help You Ward Off A Cold

Hugging It Out Could Help You Ward Off A Cold

Newsy (Dec. 21, 2014) Carnegie Mellon researchers found frequent hugs can help people avoid stress-related illnesses. 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:

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