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.

“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 July 25, 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 July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. 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