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Highly Sensitized Transplants
For one of every three kidney failure patients, a transplant is not possible even if a potential donor's tissue and blood types otherwise match perfectly. This is because they have a highly sensitized immune system that would attack the transplanted kidney or pancreas.
At the Cedars-Sinai Kidney and Pancreas Transplant Center, an innovative procedure -- intravenous immunoglobin (IVIG) therapy -- is being used to give new hope to kidney failure patients.
IVIG therapy was first adapted for use in transplantation by Cedars-Sinai researchers led by Stanley C. Jordan, MD. Cedars-Sinai holds the U.S. patent for this therapy.
Causes of Sensitization
One of the ways that our bodies protect themselves from infection is the ability to recognize and destroy foreign cells. When the blood meets a foreign cell, it produces an antibody to fight the invader.
Tissue compatibility issues exist for all patients receiving transplanted organs. Rejection risks rise dramatically for those with a high exposure to "non-self human leukocyte antigens (HLAs). This exposure results from:
- Blood transfusions
- A previous transplant
- Pregnancy. The mother is exposed to the father's antigens, which are expressed in the cells of the developing baby.
If a person has become highly sensitized, his or her immune system is hyper-vigilant to invaders -- even when the invader is a life-saving transplanted organ.
How IVIG Therapy Works
Immunoglobulins are proteins naturally produced within the body that are natural defenses against invading organisms. Intravenous immunoglobulin therapy has been used for years to treat immune system disorders.
IVIG is a processed form of immunoglobulin. It is made from blood plasma. Immunoglobulin is injected into a vein to protect the patient from infection and immune diseases.
IVIG therapy reduces HLA sensitivity by adding helpful antibodies to the patient's bloodstream. This lowers the level of HLA antibodies and blocks their ability to attack a transplanted organ. IVIG therapy can be used successfully in both adults and children seeking kidney transplants.
Unlike many anti-rejection therapies, IVIG does not suppress the entire immune system, but actually boosts the patient's protection against infection.
Adding Rituxan® Shortens Time to Transplantation
Clinical research done at Cedars-Sinai shows that adding the drug Rituxan to IVIG therapy both improves transplant rate and reduces the time needed for treatment. Rituxan reduces the number of B-cells in the body. B-cells produce the HLA antibodies. Combining Rituxan and IVIG means that treatment can be reduced from 16 to four weeks. It currently is recommended for most patients.
How IVIG and Rituxan Therapy Are Given
IVIG therapy is given in two, four-hour dialysis treatments before transplant surgery.
About two weeks after the first treatment with IVIG, Rituxan is given as an intravenous infusion over six hours.
About two weeks after transplant, a final treatment with IVIG is given. Infusion of IVIG and Rituxan is associated with few side effects. The most common complaint is headache.
If IVIG Doesn't Work
Some patients don't respond to IVIG-Rituxan therapy and continue to have high HLA antibodies that prevent them from receiving a transplanted organ. This happens about 10% of the time.
When this happens, the Cedars-Sinai Transplant Immunotherapy Program offers a therapy called plasma exchange. Plasma exchange is also known as antibody removal therapy. This approach usually requires patients to have a living donor.
Hope for the Highly Sensitized Patient
About 40% of the patients who come to Cedars-Sinai for a kidney transplant are highly sensitized. According to Dr. Jordan, between 95 and 97% can be successfully desensitized with IVIG and Rituxan.
"Somewhere between 25 to 30% of patients on the national kidney transplant list could benefit from this therapy," Dr. Jordan added.