Featured Research

from universities, journals, and other organizations

New regimen frees kidney-transplant patients from dependency on immunosuppresant drugs

Date:
October 6, 2011
Source:
Stanford University Medical Center
Summary:
Researchers have developed a novel protocol that allows kidney-transplant recipients to jettison their indispensable immune-suppressing drugs. The protocol could also spell substantial savings to the health-care system.

Investigators at the Stanford University School of Medicine have developed a novel protocol that allows kidney-transplant recipients to jettison their indispensable immune-suppressing drugs. The protocol could also spell substantial savings to the health-care system.

The researchers have reported their progress in a letter that will be published Oct. 6 in the New England Journal of Medicine. Eight of the 12 patients discussed in the small study have now been off of immunosuppressant drugs for at least one year, and in some cases for longer than three years, without any apparent damage to their new kidney -- unheard-of in patients undergoing standard transplantation procedures. None of the 12 patients has experienced kidney transplant failure or serious side effects. The withdrawal of drugs from the first enrolled patient was reported in the same journal in 2008, and the current report shows that the successful outcome has been reproduced.

In all 12 cases, recipients were supplied with immunologically matched donor kidneys from close relatives. But the trial, which has been actively enrolling new patients, is now expanding to include imperfectly matched donor-recipient pairs as well.

"Transplant recipients can ordinarily expect to be on a regimen of two or three immune-system-suppressing drugs for the rest of their lives," said immunologist Samuel Strober, MD, who is a professor of medicine and the new protocol's inventor.

"While they help ward off rejection of the new organ by the patient's own immune system, these drugs carry their own risk of side effects, such as high blood pressure, diabetes and cancer," Strober said. The drugs themselves are somewhat toxic to the kidneys, although that is far outweighed by their value in preventing immune rejection.

Moreover, immune-suppressing drugs don't always work. In those cases, the patient experiences a gradual deterioration of the donated organ until it eventually fails, necessitating another transplant operation or a lifetime on dialysis.

The new technique differs from the standard kidney-transplant procedure mainly by combining carefully targeted irradiation of a patient's lymph nodes, spleen and thymus -- thus temporarily weakening their own immune systems -- with the administration of stem cells drawn from the kidney donor's blood. These new donor cells eventually differentiate to join the components of a recipient immune system that is now much more "friendly" to the new organ than is observed in classical transplantation experience.

It took more than 30 years of mouse research, Strober said, before he finally came up with just the right mix of agents for "avoiding a civil war" among dueling immune systems. But the combination of targeted radiation and the organ donor's blood-forming stem cells -- along with antibodies that selectively deplete some of the recipient's immune cells -- suppresses immune activity that would otherwise destroy the donated kidney. Eventually the recipient's immune system returns to its pre-transplant state of readiness, "but it casts a blind eye on the foreign tissue of the graft," Strober said. As a result, after 18 months to five years of follow-up after their surgeries, recipients appear largely freed from rejecting their new organ.

More than 400,000 people in the United States are on dialysis (mechanical filtration of the blood) for kidney failure. Dialysis, while life-extending, is far from a perfect solution. Patients must spend several hours immobilized in special centers three times a week for the rest of their lives or, less commonly, receive more frequent dialysis in home rigs. Moreover, life expectancy for patients on dialysis is significantly lower than for those who successfully receive new kidneys. Dialysis is also expensive, costing close to $70,000 per patient per year.

Kidney transplantation holds out the prospect of returning to a normal lifestyle. In the United States, about 17,000 such procedures are performed each year, with many tens of thousands on the waiting list at any time. "On average, transplant recipients have twice the life expectancy of people on chronic dialysis," said co-author John Scandling, MD, professor of medicine and attending nephrologist for the patients in the study. "A transplanted kidney from a living, immunologically matched sibling can last 25 to 30 years on average with conventional treatment." (A kidney from a deceased donor will last only about half that long, at best.)

Left to itself, the patient's immune system would relentlessly attack a new organ unless it came from an identical twin. To stave off this attack, all transplant recipients are routinely placed on a regimen of immune-suppressing drugs. But in addition to their potential side effects, these drugs all too often fail to prevent organ rejection, which can be precipitous or gradual.

"Failure of a transplanted kidney is an expensive event," with an approximately $80,000 price tag to the health-care system during the year when the failure occurs, said Scandling.

The new protocol carries a total expense estimated to range from $20,000 and $40,000, so it has the potential to pay for itself within a few years. And it requires no additional hospital time.

Under the protocol, the kidney recipient receives radiation treatment and injections of antibodies while still in the hospital a few days after surgery, and additional radiation doses over the next several days on an outpatient basis. About 10 days after surgery, the recipient gets an injection of cells taken from the organ donor. All patients initially are put on two of the same immune-suppressing drugs (plus antivirals and antibiotics) that transplantation patients would normally get.

After a month, one of the drugs is withdrawn; thereafter, the Stanford team, led by Strober, continually monitors numerous parameters including the mixing of donor and recipient immune cells. If that mixing seems in balance six months after surgery, the recipient's second immunosuppressant-drug dose is discontinued. If the mixing hasn't been achieved, the patient remains on the drugs until it is.

At first the scientists thought the careful balancing act between the recipient's and donor's immune systems might need to remain intact permanently. But it now looks as though a gradual shift back toward predominance by the recipient's immune system, observed in a number of cases, doesn't cause organ rejection.

Recipients and donors in this trial are what immunologists call "a perfect match." They share identical versions of all six so-called HLA antigens, surface markers on every cell in a person's body. This lowers the risk that a patient's immune system will attack the transplanted organ. The trial -- which has been funded by the National Institutes of Health -- is now expanding to allow participation of recipient-donor pairs with as few as three matching HLA antigens. The study of perfectly matched pairs is continuing with philanthropic support from the Stanford Institute for Immunity, Transplantation and Infection. During the past year, four more perfectly matched patients received transplants, and three already stopped immune-suppressive drugs.

Additional Stanford researchers involved in the study were associate professor of surgery Stephan Busque, MD; associate professor of medicine Judith Shizuru, MD, PhD; and professor of pathology and of medicine Edgar Engleman, MD.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. The original article was written by Bruce Goldman. Note: Materials may be edited for content and length.


Journal Reference:

  1. John D. Scandling, Stephan Busque, Judith A. Shizuru, Edgar G. Engleman, Samuel Strober. Induced Immune Tolerance for Kidney Transplantation. New England Journal of Medicine, 2011; 365 (14): 1359 DOI: 10.1056/NEJMc1107841

Cite This Page:

Stanford University Medical Center. "New regimen frees kidney-transplant patients from dependency on immunosuppresant drugs." ScienceDaily. ScienceDaily, 6 October 2011. <www.sciencedaily.com/releases/2011/10/111005172637.htm>.
Stanford University Medical Center. (2011, October 6). New regimen frees kidney-transplant patients from dependency on immunosuppresant drugs. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2011/10/111005172637.htm
Stanford University Medical Center. "New regimen frees kidney-transplant patients from dependency on immunosuppresant drugs." ScienceDaily. www.sciencedaily.com/releases/2011/10/111005172637.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. 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