As UC Davis sets pace to lead the nation in lifesaving kidney transplants, a reputation for finesse and innovation earned the UC Davis Transplant Center a role at a White House summit about solving America’s organ shortage

Within the next two hours, an American is likely to die while waiting for a kidney transplant.

An average of 13 pass away each day while hoping to take advantage of the life extending procedure, according to the National Kidney Foundation, and another 10 become too sick to receive one anyway.

Unfortunately for them and their loved ones, the ebb and flow of the nation’s kidney transplant waitlist has in recent years been much more about demand than supply. While the list has grown steadily from around 60,000 people a decade ago to hover at more than 100,000 today, the rate of annual transplants has been stuck around 17,000 or less much of that time.

Average wait times are now three to five years at most of the nation’s transplant centers, and can be twice that in some regions.

Recognizing the growing emergency, the multidisciplinary kidney and pancreas transplant team at UC Davis has worked aggressively — but also carefully — in recent years to maximize the number of transplants and transplant options it can offer patients in Northern and Central California.

Along the way it has bucked national trends to emerge as one of America’s busiest kidney transplant centers, growing from fewer than 100 procedures per fiscal year a decade ago to a rate of almost a transplant a day last year. UC Davis has now ranked among the U.S. top-five centers in total kidney transplant volume in each of the last five calendar years. And if trends at the time of this November writing continue, UC Davis may top the nation this year and reach a near-historic 400 procedures.

“There’s a clear rationale for transplant because it’s lifesaving and improves quality of life — but while the wait list is growing, supply is relatively flat,” said Richard Perez, M.D., chief of transplant surgery at UC Davis and director of its kidney transplant program since 1991. “Our perspective is this really is a national crisis — so we’ve examined our program so as to operate in ‘crisis mode’ versus the status quo. We’re trying to look at every possible way to produce transplants.”

“We’re trying to look at every possible way to produce transplants.”

Besides extending individual lives directly, that activity has also led to insights, innovations and refinements that are informing efforts to boost transplant rates nationwide. Program leaders such as Perez and Angelo de Mattos, M.D., M.P.H., UC Davis’ chief of transplant nephrology, have been invited or welcomed to share or craft best practices in several national forums aimed at reducing the country’s organ imbalance, such as a White House summit last June on the role of science, technology and innovation in reducing waitlists.

“It’s not just ‘business as usual’ anymore,” said Perez, who represented the UC Davis program at the event. “We’re not interested in just doing things like we used to — we’re looking at everything, and working to develop creative solutions.”

Removing barriers

Perez himself knows firsthand about the power of leaps in transplant medicine: his father received a heart transplant at Stanford in 1982, and was in the first wave of cases to benefit from the new immunosuppressive drug cyclosporine, a major advancement that helped spur new organ transplant programs around the country.

Kidneys have since become the organ most in demand, representing almost 85 percent of the nation’s overall 120,000-strong waitlist. Meanwhile more than 630,000 Americans have end-stage renal disease or kidney failure, and 26 million Americans overall are estimated to be at some stage of chronic kidney disease, whose main U.S. causes are diabetes and hypertension.

Transplantation is the treatment of choice for most kidney failure patients, according to both the National Kidney Foundation and the American Society of Transplantation. While dialysis can sustain life, transplantation can add life years and significantly improve quality of life in patients with renal failure.

There’s generally consensus that it will take increases in both live- and deceased-donor transplants to solve the nation’s kidney crisis, but how to go about achieving those gains is a matter of imposing complexity. Discussion and debate touches on technical issues in surgery and medicine but also on matters of administration and allocation, reimbursement, biomedical ethics and politics.

Improving live donation

The UC Davis program has a three-decade history of harnessing innovation in both live- and deceased donor transplant to increase the volume and variety of life-extending options for area patients.

Live-donor transplants were a major focus here and across the nation in the 1990s because of their superior outcomes, for example, but the 18-inch scars from surgical techniques of the day were a disincentive to donors. When a Johns Hopkins surgeon (also a recent UC Davis guest lecturer) described the first laparoscopic live-donor nephrectomy in 1995, Perez embraced the gentler minimally invasive technique and helped to pioneer it, with UC Davis building the largest series of such procedures on the West Coast for several years.

Fellow UC Davis surgery professor Christoph Troppmann, M.D., also published early at the time on the safety of live donor laparoscopic nephrectomies involving multiple arteries, and UC Davis was the first to publish on a series of laparoscopic donor kidneys for pediatric patients. Troppmann again served as an early adopter in 2011 when he became one of a handful of U.S. surgeons to offer the even less invasive single-port nephrectomy procedure, which removes a live donor’s kidney through a single, tiny incision with typically shorter recovery times.

To ensure that no willing donor’s generosity goes to waste, the UC Davis program has also advanced therapies in desensitization and paired-donor exchanges this decade in order to use kidneys from previously incompatible donors.

UC Davis has collaborated with hospitals and transplant registries nationwide to coordinate more than 40 complex paired exchanges, for example, which help unmatched donor-recipient pairs to find matches by swapping the living donors. Nearly 400 people were involved in making one particularly elaborate type of exchange, a four-way “domino chain,” possible in 2014.

Stockton resident Mike Navarec received a kidney in that chain when he and his daughter Michelle Roley signed up for exchange after learning their blood types weren’t compatible. Navarec, a Catholic deacon, received a kidney from another woman in the chain while his daughter’s organ went to a waitlisted man.

“When I heard the stats and how much more successful live donations I thought immediately about being a donor,” Roley said. “I never really had any reservations or fears at all, and I had a very successful recovery with very little pain and no complications. It’s a blessing to be able to become a donor — it’s life-changing, really.”

Navarec, 70, now has the freedom to travel overseas and enjoy other activities that were off-limits before. On the one-year anniversary of his transplant he took his family on a cruise as a celebration of life.

“It’s just phenomenal what the results are for the person who receives the transplant, but also I’d say for the person who gives as well — you can also have a great relationship (with your recipient),” he said. “The experience also brings your family together and shows the importance of how a person will give a part of themselves — an actual part of themselves — to help another have a better life.”

Sharon Stencel, the coordinator of the UC Davis living kidney donor program who was instrumental in the chain, knows that firsthand. Stencel, a nurse donated one of her own kidneys to a relative two years ago and triggered a paired exchange involving a donor and recipient in Florida. Today she uses insights from her experience to help guide UC Davis patients as they navigate the process of becoming a live donor.

Window of opportunity

As live-donor efforts continue in earnest, in recent years UC program leaders have also recognized deceased-donor organs as a key opportunity to increase options and reduce wait times for local patients. Deceased-donor organs currently make up the majority of UC Davis transplants and the program is presently the national leader in the field, having consistently performed the country’s highest volume four of the past five years.

By building relationships with organ-procurement organizations around the country and innovating in the utilization of more challenging organs, the UC Davis program has in particular been able to harness kidneys that other U.S. centers may lack the expertise to use successfully — and do so without detriment to its outcomes. The majority of deceased-donor kidneys used by the program are imported from outside its local procurement area, and it also welcomes harder-to-place organs such as kidneys from small pediatric donors and those donated after circulatory death or classified as “extended criteria” due to a donor’s age or history of hypertension, kidney illness or stroke.

The more challenging kidneys can have their limitations but can literally be lifesaving to some people who otherwise would not have access to transplantation. Kidney failure patients make a personal choice about whether to accept them when they sign up for waitlists, weighing the pros and cons in relation to their quality-of-life goals and expected remaining lifespan on dialysis.

Extended criteria organs can typically come with some risk for earlier graft loss, for example; some estimates assume half may still function after five years, compared to seven of 10 optimal or “standard criteria” kidneys. But accepting an extended criteria organ may also significantly decrease time to transplant — a potentially lifesaving factor for many older or frailer recipients who may be statistically likely to perish within average waiting periods.

Finessing challenging organs into service has in part allowed the UC Davis program to offer the shortest average transplant wait time in Northern California the past five years, with wait times often less than half of regional, state and national averages and significantly better-than-expected waitlist mortality.

“It’s our position that every possible kidney that can be successfully used for transplant should be used for transplant in order to reduce waitlist times,” Perez said. “We commit the resources to fully test all of our kidneys in advance — including unconventional kidneys — to determine their transplant status, and then ensure they’re matched with the best possible recipients. We also provide full and close medical support following transplant.”

Sacramento resident Maple Avery went from enjoying tennis, volleyball and half-marathons at age 65 to pain, mobility limitations and extreme fatigue after kidney failure set in three years later. After eight months on dialysis, the memory care supervisor received two kidneys at UC Davis that were sourced from an older deceased donor and ruled out for single use elsewhere.

“I was glad to get them,” said Avery, now back at work at 73 and an active senior volunteer. “I’d become aware of children and younger people who need kidneys, and I thought ‘Why give me the kidney of a 12- or 15-year-old who just passed away, when there are others in their twenties or thirties who need (younger organs) to live longer?’ ”

Last year Avery and UC Davis transplant staff thanked organ donors nationwide in a Discovery Channel video public service announcement for “Project Thank You,” a month of gratitude-based programming. Avery was joined in the video by her daughter Cherysse, who independently moved to Sacramento to provide emotional support for her mother during treatment.

“If I can stay alive for a while longer I can be thankful, because I can see my daughter and grandchildren accomplish what they want to,” Avery said. “Maybe I won’t see their whole lives, but the part I do see would be satisfying and allow me to say that I’ve made a contribution.”

Risk-reward

Harder-to-place organs are considered an important part of the national solution by major organizations such as the American Society of Transplant Surgeons, the National Kidney Foundation, the Organ Donation and Transplantation Alliance and the American Society of Transplantation. The latter organization for example has called for expanded professional education programs to optimize use of expanded criteria organs and those donated after circulatory death.

But in practice their use can also represent a thornier proposition for some individual centers because of higher risks for delayed graft function, rejection and other surgical complications. At this summer’s White House summit the AST also announced grants for research on transplant center performance metrics, with a goal of “reducing undue risk aversion and incentivizing innovation in transplantation, while maintaining patient safety and care.”

Despite embracing the challenges of using hard-to-place organs, UC Davis has preserved generally excellent — and sometimes nationally significant — overall postsurgical outcomes for its patients in recent years, maintaining overall one- and three-year patient and kidney survival rates that equal or exceed the expected outcomes based on national data. The stats are a tribute in large part to exceptional post-transplant care provided by the center’s nephrology lead team, Perez said; the overall UC Davis adult and pediatric nephrology programs ranked among the country’s best in U.S. News & World Report 2016–17 ratings, with the adult program placing tenth.

“These organs are more resource-intense, and they require more assessment, but we look very closely and match them to the appropriate patients,” Perez said. “We are also very, very data driven — we look at our data very closely and look for opportunities to improve. When we find them, we make the change, increase our risk incrementally, and then reassess.”

The UC Davis program is now helping to shape national consensus practice in the area. For example, de Mattos and transplant surgeon Chandrasekar Santhanakrishnan, M.D., M.P.H., are playing a consultative role in a transplant-focused Collaborative Innovation and Improvement Network or COIIN, a three-year federally funded pilot project to assess effective practices for utilizing hard-to-place kidneys that maintain quality outcome measures. UC Davis is one of 11 “practice model hospitals” where officials are studying methods for potential wider sharing.

UC Davis staff also helped to plan a National Donor Alliance critical issues conference in October to identify novel collaborations and strategies to increase transplantation, and will participate in a National Kidney Foundation consensus conference next fall on minimizing kidney discard rates.

“We’re extremely proud that the efforts of our transplant nephrology section, and our close collaboration with surgeons, have contributed to improved outcomes here in this era of nationwide organ shortage,” de Mattos said. “And we’re proud of the expanded access our outreach clinics have created for patients throughout Northern California, the Central Valley and northwest Nevada, and the effect on helping to mitigate geographic and economic disparities.”

Extra TLC

Perez credits multiple factors for the UC Davis program’s combination of volume and results, among them depth and breadth of expertise (many team members have been with the program for a decade or more), more extensive methods of assessment and care, and the pairing of innovation with close performance monitoring.

“Part of the success is having a large and seasoned team that’s been here a long time as the foundation of things — that depth and breadth and stability has enabled us to provide a strong medical and surgical focus,” Perez said. “It also applies to the whole environment, including the operating room, the transplant inpatient ward and our nurses and administrators in the Transplant Center — a lot of our staff ends up staying a long time because the work is so gratifying. And the program is truly multidisciplinary — we benefit from incredible talent in radiology, cardiovascular services, infectious diseases and other key areas.”

The program pairs its human expertise with insights derived from the use of cold pulsatile perfusion pump technology, a more expensive and time-consuming but ultimately more insightful method of preserving deceased-donor organs and determining their viability. UC Davis was an early adopter of the technology, which replaces passive cold storage of kidneys by using machinery and a cold preservation solution to mimic blood flow through the organ. The process creates indicators that are then compared against data-driven criteria for transplant.

UC Davis observations are now helping to refine national standards for optimal pump time, settings and temperatures in cold pulsatile perfusion, Perez said, and adoption of the more resource-intense technology has gradually been gaining traction nationwide as data arrives linking it to increased long-term survival. Meanwhile his lab is also researching other novel ways to improve the technique, including a pump that links aspects of perfusion and extracorporeal life support systems (see research sidebar).

“Pulsatile perfusion gets kidneys to work earlier initially after transplant, and can help preserve organs longer, and gives another, better way to assess a kidney,” Perez said. “We knew it could open the door to perform both more transplants and also better-risk transplants.”


An extra hand before transplant

While nearly 5,000 Americans pass away each year waiting for a kidney transplant, as many as 3,000 kidneys annually are removed from deceased donors with intent to transplant — but then discarded.

“It’s the right thing to do if you don’t think the organ will work or it’s too high-risk,” said Richard Perez, chief of transplant surgery at UC Davis and director of its kidney and pancreas transplant program. “But some of these organs could also be rescued if we had a better system to assess and restore them.”

Perez and the UC Davis transplant program were successful early adopters of one such method, known as cold pulsatile perfusion. Now Perez is testing an improved version of the assessment system that he hopes will provide specialists with even better means of evaluating deceased-donor organs, rehabbing them when needed — and ultimately rescuing more for transplantation.

The hybrid system, called normothermic perfusion, uses a pediatric extracorporeal life support machine to perfuse kidneys with red blood cells at normal temperature, instead of the cold preservation solution used in pulsatile perfusion (centers that do don’t use pulsatile perfusion simply keep the organs “on ice”).

The thought is that the warm blood in the transfusion-like process will offer twofold benefits, the first being a more comprehensive and detailed measurement of function. “We knew that cold pulsatile perfusion could open the door to perform both more transplants and better-risk transplants, but the disadvantages are that in the highest-risk cases you still can’t predict with certainty if the kidney will work or how well it will work,” Perez said. “That’s where normothermic perfusion comes in. You are actually simulating the transplant — warming the organ up, running blood through it, providing nutrients and oxygen — resulting in the kidney even generating urine while on the machine.”

When the additional assessment with normothermic perfusion shows that a kidney is injured due to the late donor’s health, it’s also hoped blood-based perfusion will allow specialists to rejuvenate organs when needed to improve their potential for use. Perfusing with blood already delivers oxygen that helps to repair kidneys, and it can be used to deliver additional interventions such as anti-inflammatory drugs or stem cells to enhance reconditioning more when needed.

Perez and his research team have tested 50 kidneys otherwise destined for discard, and preliminary data suggests significant improvement in injury markers following even short courses of normo-thermic perfusion. UC Davis staff presented abstracts on their efforts at this summer’s American Transplant Congress, and Perez hopes to begin formal clinical safety and efficacy trials next year. Normothermic perfusion has been used by many U.S. institutions for lung, heart and liver, but kidney use has been limited to date to a single group in England.

If successful, Perez believes the new system could help spur the creation of centers whose total focus and expertise is testing, rejuvenating and reconditioning organs for use by transplant hospitals.

“So far (normothermic) testing is leading us to believe there are many more kidneys that can be used for transplant that are currently discarded,” Perez said. “We’re really focused on moving this technology to the forefront, because we think it will help ease the nation’s shortage even more.”