The first doctors she consulted told Rachel Amato that the odds were vastly against her ever having a successful kidney transplant.

Then the 29-year-old mother of four from Turlock, California, traveled to Stanford Hospital & Clinics. "They were really honest with me," she recalled. "They said, 'We have seen proof that this new treatment works. We just don't know how many doses it's going to take.'"

In August 2008 Amato had her first four-hour infusion of a "desensitization" drug, intravenous immunoglobulin, or IVIG, designed to lower the number of organ-rejecting antibodies in patients who are highly "sensitized." That means they have weapons-grade antibodies—acquired in blood transfusions, pregnancies or during a previous transplant—that seek out and destroy invading antigens, particularly the human leukocyte antigens, or HLA, on the surface of a foreign organ. These patients' immune systems would reject a donor kidney.

Amato had one infusion per month for four months, and in January 2009 she had a dose of an additional drug, Rituxan, which knocks out many of the immune-system cells that produce antibodies. "Boom! My antibodies dropped," she said. "I got my transplant two weeks later."

The desensitization program, as well as improvements in minimally invasive surgery and the promise of an experimental "tolerance induction" protocol, have placed Stanford Hospital & Clinics at the forefront of kidney transplant programs. It was the only one among 240 kidney transplant centers nationwide that exceeded expected results in both patient and graft (transplant kidney) survival at one year and at three years after transplantation, according to data reported by the independent Scientific Registry of Transplant Recipients, or SRTR. The registry's data also shows that Stanford was the top program in one-year transplant kidney survival rates for four years running, from July 2000 to June 2004.

"It's not just a fluke," Stephan Busque, MD, surgical director of the adult kidney and pancreas transplant program, said about the latest SRTR data. "Even though we're treating patients at higher risk, we perform better than expected because we have a very good team and our patients get very attentive, individualized care."

Busque and nephrologist John Scandling, MD, medical director of the program, have been pursuing new tests, treatments and technologies that will get more patients to transplantation.  That effort received a boost when they recruited Dolly Tyan, PhD, to direct Stanford's Histocompatibility, Immunogenetics and Disease Profiling Laboratory in 2006. Tyan had co-developed a program at Cedars-Sinai Medical Center in Los Angeles that addresses the plight of people who, like Rachel Amato, need transplants but can’t qualify for them because they are "highly sensitized."

The new protocol involves giving these high-risk patients a high dose of IVIG. The IVIG infusions, which may be repeated over several months, lower the number of organ-rejecting antibodies in patients awaiting transplants. "If we lower their antibodies after the first dose, we assume by the second dose they’re going to be lowered more," Tyan said. "So we schedule the OR time, we give the dose and then they go to transplantation." 

Tyan estimates that 30 percent of the 80,000 people on the national waiting list are HLA sensitized, and potentially could benefit from being desensitized by the IVIG protocol. The treatment currently is available at only a handful of other medical centers, including Cedars-Sinai, Johns Hopkins, the Mayo Clinic and the University of Toronto. Tyan and her colleagues also have developed a new assay system that "allows us to see very specifically what antibodies a person has, and exactly which ones are going to go away."

The hot topic at this year's annual meeting of the American Transplant Congress, Tyan said, was how to control antibodies. But she was quick to add that the "holy grail" of transplantation remains tolerance. "That's  'true' tolerance, which means, 'I'm not taking any meds and my [transplanted] organ is working fine.'"

Stanford and Harvard University currently are the only two academic medical centers in the United States that have active clinical tolerance-induction protocols. Ten transplanted patients at Stanford are enrolled in an NIH-funded clinical trial, directed by Samuel Strober, MD, professor of immunology and rheumatology, to wean them off immunosuppressant medications. "It draws a lot of interest from patients because the appeal of having to take no drugs is tremendous," Scandling said about the study, while noting that the experimental therapy is a long way from becoming routine care.

In the meantime, Amato is grateful that she had the opportunity to get a kidney. While she still takes medication to ensure against her body's rejecting the organ, her life is almost back to normal. She had a migraine headache after the first infusion, and one rejection episode that hospitalized her for five days and was addressed by the team at SHC. "They had all these game plans ready," she said.

Nowadays Amato has her antibodies tested once a month, and she said she is doing great. "I have a rare autoimmune disease—not hypertension induced, not diabetes related," she said. "Stanford was my saving grace because they did not give up on me."

By Diane Rogers