Kidney Transplant: Stem Cells Eliminate Need for Anti-Rejection Drugs

March 7, 2012— -- Lindsay Porter knew she would eventually need a kidney transplant. She was 19 years old when her mother died from polycystic kidney disease -- a genetic condition that Porter had 50/50 odds of inheriting, and did.

"It didn't really affect me much until my early 30s," said Porter, an actress and mother living in Chicago. "And as I got into my 40s, my kidneys started getting very big with multiple cysts. They were huge."

Porter's kidneys weighed 16 pounds, causing an obvious bulge in her tiny frame.

"It was like two full-term babies inside me," she said, adding that people often mistook her for pregnant. "They had to be removed."

In May 2010, doctors removed Porter's overgrown and failing kidneys. Two months later, a friend gave her one of his. But it was no ordinary transplant. Along with the fist-size organ, doctors at Northwestern Memorial Hospital in Chicago transplanted bone marrow stem cells -- an experimental procedure they hoped would eliminate the need for anti-rejection drugs.

"These drugs are currently an absolute necessity, but they have a downside," said Dr. Joseph Leventhal, Porter's transplant surgeon at Northwestern Memorial Hospital and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine.

Anti-rejection drugs suppress the immune system, preventing it from attacking the donated organ like an infection. But suppressing the immune system makes the body vulnerable to infections and even cancer. And the drugs, which carry toxic side effects, can't ward off rejection forever. "Many individuals will still lose their transplants over time due to chronic rejection," said Leventhal.

To coax Porter's body into recognizing the new kidney as her own, Leventhal and colleagues wiped out part of her immune system and replaced it with the donor's. It took four days of chemotherapy, whole-body irradiation and a bone marrow transplant -- no walk in the park, according to Porter. But over time, the donor bone marrow stem cells gave rise to immune cells that accepted the kidney as if it was Porter's own -- a process called induced immune tolerance.

"At first I was taking 24 pills a day," said Porter, describing the "cocktail" of anti-rejection drugs needed to fend off an attack on her new kidney while the bone marrow stem cells were setting up shop. "And you really can't miss a dose. I had to set my cell phone alarm for every 12 hours every single day to remind me."

After six months, Porter started weaning herself off the drugs. And after a year, she no longer needed them at all.

"My life is totally transformed," she said. "It's like I never even had kidney disease, never even had the transplant. It's so easy to feel normal and forget it even happened."

Porter is one of eight patients who participated in the kidney transplant trial run jointly by Northwestern Memorial Hospital and the University of Louisville. Five of the patients, including Porter, now have chimeric immune systems consisting of their own immune cells and immune cells from their donor. They no longer need any anti-rejection drugs. Two patients had "transient chimerism," meaning it didn't last, but take half the anti-rejection drugs they would have needed without the stem cell transplant. One patient had complications from the transplant.

The results of the trial, which is ongoing, were published today in the journal Science Translational Medicine.

Hope for Life Without Anti-Rejection Drugs

Dr. Suzanne Ildstad, director of the Institute of Cellular Therapeutics at the University of Louisville, pioneered the approach and led the trial with Leventhal.

"It really makes all work we've done really worthwhile," she said. "Being a transplant recipient isn't easy. They have to take up to 25 pills a day, keep track of them, suffer the consequences of them. There's really been no other way. ... These results are really gratifying."

Eliminating the need for anti-rejection drugs would mean healthier transplant recipients and longer-lasting organs.

"We would love for the first transplant a person gets to be the only transplant they need," said Leventhal, adding that many transplant recipients need a second transplant in their lifetime because of chronic rejection. "We hope that tolerance will be a pathway toward keeping that transplant for as long as they live."

This year, Leventhal and Ildstad will test the approach in patients who have already received a kidney transplant from a living donor. They hope transplanting bone marrow stem cells from the same donor even years after the organ transplant will reduce the need for anti-rejection drugs. They also plan to broaden the study to include other types of transplants.

Porter, now 47, is making the most of her new life free of kidney disease and anti-rejection drugs.

"I used to save my best hours to do something with my son," she said, describing the fatigue she felt during 5-year-old CJ's early years. "Now we're constantly running around on all kinds of adventures. ... I feel like someone just shaved 15 years off me. I went from feeling old to feeling great."

After losing loved ones to hereditary kidney disease, Porter said she is grateful to have had the chance to participate in the pioneering trial.

"This was some small thing I could do to honor them," she said. "Someone has to do it first."