November 16, 2009
“I’m a demanding person,” says Daniel Brennan, MD, Washington University transplant nephrologist. “I think this inspires others to give their best for our patients.”
It’s hard to argue otherwise.
Since Dr. Brennan arrived in 1993 to direct Washington University’s transplant nephrology program at Barnes-Jewish Hospital, its one-year kidney rejection rates have plummeted to 5 percent compared to the national average of 15 to 20 percent. The kidney transplant program’s rate of delayed function after transplant is now less than 10 percent, which is much lower than the national average of 25 to 30 percent.
Dr. Brennan’s research has influenced the way many physicians around the world prevent acute kidney rejection, and may even change the way long-term effectiveness of new treatments is studied in other fields of medicine. Pivotal steps of Dr. Brennan’s research began with grants from the Barnes-Jewish Hospital Foundation.
The First Breakthrough
Dr. Brennan began his research by looking at the state and standards of induction therapy, in which patients are given medication during and immediately following transplant surgery to help suppress the immune system response that causes organ rejection.
“In 1993, only 10 percent of kidney transplant programs nationally used induction therapy,” Dr. Brennan says. “Many types of induction were used, but the one we used – a drug called OKT3 – was narrowly targeted and caused many side effects, like fever and fluid in the lungs.”
He continues: “I thought induction therapy could be more effective if we used, at an earlier time, agents that caused broader immune suppression. This would allow us to prevent rejection while lowering long-term, maintenance suppression that can compromise the immune system, leading to infection and cancer.”
So Dr. Brennan and his team compared a broader spectrum drug called ATGAM to OKT3. They found that while overall costs were similar, the rejection rate with ATGAM was lower.
But Dr. Brennan thought they could do better. He had an idea about thymoglobulin, a drug derived from rabbits. This time, he turned to the Foundation for support.
Hitting Mach 4
The result of Dr. Brennan’s Foundation-funded study comparing thymoglobulin to ATGAM was staggering. “We achieved a 4 percent rejection rate at one year, when other programs were achieving 25 to 50 percent rejection rate,” Dr. Brennan says. “This was Mach 4!”
The medical community was originally skeptical. But Dr. Brennan stayed focused and built a research environment considered by peers to be among the best at researching kidney transplant through randomized clinical trials.
Today, 70 percent of kidney transplant patients nationally receive induction therapy – and more than half receive thymoglobulin.
“No One Expected a Long-Term Impact”
Dr. Brennan’s team then studied the prolonged effects of induction therapy. “Many physicians believed that induction therapy bought you some time,” Dr. Brennan says. “But no one expected a long-term impact.”
The challenge was cost: building a database and reaching all of the original patients five years later would require more than $1 million. But inspiration struck again. What if, thought Dr. Brennan and his team, they could study information in the database maintained by the United Network of Organ Sharing/Organ Procurement and
Transplantation Network (UNOS/OPTN).
“All U.S. transplantation centers are mandated to enter data in the UNOS/OPTN database yearly,” Dr. Brennan explains. “The database has been tested, it’s accurate and it’s open to all researchers.”
Using the less costly UNOS/OPTN records, Dr. Brennan’s team found that the effect and advantage of thymoglobulin over another widely used, targeted induction drug was better and did not wear off over a five-year period. The cost of this study? $20,000.
“The direct importance of our study is that we’ve been able to show the advantages of thymoglobulin for induction therapy,” Dr. Brennan says. “But we’ve also proven that this methodology is a cost-effective way to study long-term effects of any type of treatment. It could be used in any field for which registry data is available from clinical studies.”
Start-Up Support Was Essential
Dr. Brennan is clear about where his successful research career began.
“I could not have done it without start-up support from Washington University and the Barnes-Jewish Hospital Foundation,” he says. “The National Institutes of Health would not fund this kind of work, nor would many drug companies. Barnes-Jewish Hospital Foundation grants supported my first steps.”
“Would I Want to Be My Doctor?”
“Transplant medicine is so rewarding,” Dr. Brennan says. “You see people who are sick, on dialysis…then they get a transplant and are transformed. Sometimes the transplant fails, but with the work being done today, this will happen less often.”
He evaluates himself carefully. “I look in the mirror and ask myself, ‘Would I want to be my doctor?’ It inspires me to do anything that I possibly can for the patient.”
The entire kidney transplant team shares his commitment. “People should come to Barnes-Jewish for kidney transplant because our team approach achieves the best results,” Dr. Brennan says. “For all of us, it’s not just a job – it’s a profession in which we have an opportunity every day to make a difference for someone else.”
Mentoring for the Future
Looking to the future, Dr. Brennan hopes to study how to withdraw suppression of the immune system after a patient returns to dialysis so that he or she does not become sensitized – hypersensitive to particular antibodies – which would prevent a new transplant. He also plans to join an international study on the ability of vitamin D to prevent scarring and improve outcomes after kidney transplant. But his greatest ambition is to shape the physicians who will follow in his footsteps.
“My real dream is to train younger people and make them as enthusiastic about kidney transplant as I am,” Dr. Brennan says. “I have a great mentor in Dr. Greg Storch, and that mentorship has forged my career in many ways. I want to pass it on.”
From Barnes-Jewish Hospital Foundation’s Giving Magazine, 2009, Issue 2