Stanford Medicine Newsletter Updates For the Local Community

 

A delicate balance

New protocol eliminates kidney transplant drugs

Samuel Strober, MD, is refining a process that eliminates the need for the many immunosuppresant drugs normally required after a transplant.

   

Organ transplants can give patients a new lease on life. But to your immune system, the donated organ is a foreign invader.

Carrying an organ that originated in someone else’s body means a lifetime regimen of drugs that work to keep your own immune system from attacking the new organ. These drugs are costly and can have serious, sometimes life-threatening side effects.

Stanford researchers are making steady progress in finding ways to give kidney-transplant patients a life without immune-suppressing drugs. A unique protocol, developed by investigators at the School of Medicine, aims to let kidney-transplant recipients jettison their indispensable medication. Its success also could spell substantial savings to the health-care system.

Free from medication

Eight of 12 patients in a clinical trial of the new approach have been off their immunosuppressant drugs for at least a year, without any apparent damage to their new kidneys. This is unheard of in patients undergoing standard transplantation procedures. Not one of the patients has experienced kidney transplant failure or serious side effects.

In all 12 cases, recipients received tissue-matched donor kidneys from close relatives. But the trial is now expanding to include imperfectly matched donor-recipient pairs as well.

A hybrid system

“Transplant recipients can 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, a professor of medicine and the inventor of the new protocol. “While they help ward off rejection of the new organ, these drugs carry their own side effects, such as high blood pressure, diabetes and cancer.”

Plus, immune-suppressing drugs don’t always work. A patient may experience a gradual deterioration of the donated organ until it eventually fails, necessitating another transplant or a lifetime of dialysis.

The new technique differs from the standard kidney-transplant procedure by combining carefully targeted irradiation of a patient’s lymph nodes, spleen and thymus—temporarily weakening their immune system—with the use of stem cells drawn from the donor’s blood.

The stem cells eventually differentiate to form numerous types of immune cells, which join with the recipient’s cells to form a “hybrid” immune system that is more “friendly” to the new organ.

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.

Numbers in need

More than 400,000 people in the United States with kidney failure are on dialysis, which mechanically filters the blood. While life-extending, dialysis 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 receive more frequent dialysis at home. 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.

In the United States, about 17,000 kidney transplants are performed each year, with tens of thousands on the waiting list. “On average, transplant recipients have twice the life expectancy of people on chronic dialysis,” said John Scandling, MD, a professor of medicine and the nephrologist working with patients on the study. “Failure of a transplanted kidney is an expensive event,” he said, with a price tag of about $80,000 during the year the failure occurs.

The cost of the new protocol is estimated between $20,000 and $40,000, and requires no additional hospital time.

Under the protocol, the kidney recipient receives radiation treatment and injections of antibodies 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.

Gradual process

All patients initially are put on two of the same immune-suppressing drugs (plus antivirals and antibiotics) that transplantation patients would normally receive. After about a month, one of the drugs is withdrawn. If the mixing of donor and recipient immune cells seems in balance six months after surgery, the second immunosuppressant-drug dose is discontinued.
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 doesn’t cause organ rejection.

Patients can learn more by contacting the study coordinator, Asha Shori, at ashas@stanford.edu. For more information about Stanford’s kidney transplant program, visit stanfordhospital.org/kidneytx.

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