Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multi-center study finds therapy boosts kidney transplants in ’highly sensitized’ patients

09.12.2004


Although transplantation is by far the preferred treatment option for patients with end-stage renal disease (ESRD), those with high levels of "anti-donor" antibodies have had little hope of receiving a donated organ. Among the relatively few who have undergone transplantation, rejection rates have been very high.



Because the immune systems of "highly sensitized" individuals initiate a rejection response against the tissue of the majority of the population, these patients typically spend the rest of their lives undergoing kidney dialysis several times a week – a painful, costly process that extends life but usually results in a diminishing quality of life.

Now, a 12-center study, funded in part by the National Institutes of Health and reported in the December 2004 issue of the Journal of the American Society of Nephrology, found that an immune-modulating therapy pioneered for transplant patients at Cedars-Sinai Medical Center reduced high antibody levels and improved transplantation rates. The analysis was based on the experiences of 98 highly sensitized patients who were administered either the medication, called intravenous immunoglobulin (IVIG), or a placebo while awaiting transplantation.


"The study showed that there was a significant benefit of IVIG over placebo. In fact, the rates of transplantation for the IVIG group were more than double that for the placebo group. And for patients who had had a previous transplant – which is a very big risk factor for not being able to have another one – the IVIG group’s transplant rate was triple that of patients on placebo," said Stanley C. Jordan, MD, director of Pediatric Nephrology & Transplant Immunology and medical director of the Renal Transplant Program at Cedars-Sinai.

"Most other anti-rejection drugs can make the patient more susceptible to infectious complications because they are globally immunosuppressive," said Dr. Jordan, the study’s principal investigator, the article’s senior author and a professor of pediatrics at the University of California, Los Angeles. "The good thing about IVIG is that it modulates the immune system, it doesn’t suppress it. It appears to ’turn off’ deleterious immune responses without damaging the immune system, and in fact, it strengthens the immune system because it provides antibodies to infectious agents as well."

Although tissue compatibility issues exist for all patients receiving transplanted organs, rejection risks are especially high for a patient who has the added barrier of an immune system that has been exposed to "non-self" human leukocyte antigens (HLAs). Exposure may occur through blood transfusions, earlier organ transplantation or even pregnancy, when the mother is exposed to antigens from the father expressed in the cells of the developing baby. The immune system is then "sensitized" to those antigens – primed with antibodies to attack, even if the antigens arrive in the form of a potentially life-saving donated organ.

The degree of sensitization is measured in terms of "panel reactive antibody" or PRA levels. For a non-sensitized patient with end-stage renal disease, the wait time for a cadaveric transplantation averages four to five years. For sensitized patients, the odds of being transplanted drop. According to the article, "the higher the PRA, the more difficult it becomes to find an immunologically compatible match. Transplant rates are lower for sensitized patients and the waiting times for a compatible crossmatch are longer. Furthermore, while many of these patients may have living donors, transplantation cannot proceed …."

In 2000, fewer than 3 percent of all kidney transplants were performed in patients with PRAs higher than 80 percent at the time of transplant, despite the fact that these patients represent about 20 percent of those on the waiting list. In fact, transplant rates for these patients have gone down over the past decade as antibody detection techniques improved and waiting lists for the limited number of donor organs grew.

Dr. Jordan began to develop the concept of using immunoglobulins in a transplant environment in the late 1980s as IVIG was becoming established as a therapy for immune system disorders. The proteins, naturally produced in the body, can act as antibodies – natural defenses against invading organisms called antigens. A processed form of immunoglobulin made from blood plasma can be administered to boost the body’s natural levels.

Researchers led by Dr. Jordan have published several studies showing that IVIG therapy increases success rates for patients receiving cadaver organs as well as organs donated by relatives or friends. They also have developed a lab test that enables them to predict which patients will most likely benefit from IVIG. If IVIG changes a poor match into a more compatible one in the lab, it likely will help the patient’s immune system accept a transplanted organ.

The new study results showing that IVIG can make transplantation available to many patients who previously would have lingered on dialysis comes just months after some Medicare and other insurance providers began offering coverage for IVIG therapy in certain situations. Using IVIG to get even half of the sensitized patients transplanted and off of long-term dialysis would bring huge savings, according to cost analyses.

"From a financial standpoint and from a quality of life standpoint, there is no question that IVIG therapy and transplantation have more to offer than years of dialysis," Dr. Jordan said.

Sandra Van | EurekAlert!
Further information:
http://www.cedars-sinai.org

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>