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Surgical success

It was the first sign of trouble.

Oliver Senger was barely seven months old in 1997 when his parents noticed he was having trouble keeping his food down.

"It coincided with the time that I started giving him a bottle for some feeds," says his mom, Arnie, who lives with her husband, Brent, and their family on a grain farm near Saskatoon.

The couple thought their infant son might have a digestive problem, so they made an appointment to see their family doctor. He in turn, ordered a barium swallow test and an abdominal ultrasound.

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Kidney transplant patient Oliver Senger is prepared for surgery.

Kidney transplant patient Oliver Senger is prepared for surgery.

It was the first sign of trouble.

Oliver Senger was barely seven months old in 1997 when his parents noticed he was having trouble keeping his food down.

"It coincided with the time that I started giving him a bottle for some feeds," says his mom, Arnie, who lives with her husband, Brent, and their family on a grain farm near Saskatoon.

The couple thought their infant son might have a digestive problem, so they made an appointment to see their family doctor. He in turn, ordered a barium swallow test and an abdominal ultrasound.

Immediately after the ultrasound, the couple was asked to return to their doctor's office for the verdict: Oliver had abnormally small kidneys, a rare condition that ultimately hampers the kidneys' ability to filter waste from blood.

The boy was admitted to Royal University Hospital in Saskatoon under the care of an adult nephrologist. What followed was an intense four days of tests, blood work and worry. Oliver was losing weight and crying from headaches. He was sleeping almost around the clock and not eating. Tests would eventually confirm that Oliver's small kidneys were not fully functional.

By the end of that first hospital stay, it was determined that Oliver should travel to Winnipeg to consult with kidney specialists at the Winnipeg Health Region's Health Sciences Centre. As one of the largest jurisdictions of its kind in Canada, the Region is responsible for providing specialty referral services to residents from Nunavut, eastern Saskatchewan and Northwestern Ontario. More importantly to the Sengers, the Region's pediatric and adult kidney transplant programs have also gained an international reputation for innovation. In addition to providing quality care, many members of the pediatric and adult-care programs are involved in leading-edge research.

The turn of events left the Sengers in a state of shock. "Every parent hopes and expects to have healthy children, so finding out that a child is sick leaves you feeling helpless," says Arnie.

It was during that trip to Winnipeg that Arnie and Brent came to understand that Oliver would need a kidney transplant. They just didn't know when. Children with kidney problems who do not need a transplant in the first few years of life can often go without one until puberty.

Oliver would be one of these children. Over the next decade, the family would trek to Winnipeg at least three times a year - an 800-km trip from their home over often slippery and snow-covered highways. During his visits to HSC, Oliver would undergo a number of tests to check on the status of his kidneys. He'd also have an X-ray at least once a year to determine his bone health.

Over the years, Oliver's ailing kidneys worked well enough to keep him out of the operating room. But that changed in 2008 when they started to show signs of serious decline. It was now clear the young boy would soon need a kidney transplant. Fortunately, his father, Brent, was deemed to be a good match as a donor, and the operation was booked.

On January 6, 2011, father and son underwent the operation to transplant one of Brent's kidneys into Oliver. The operation was a success. Seven weeks after surgery, Oliver went downhill skiing with his family in British Columbia. Today, he's a healthy 14-year-old who is growing, can eat without restrictions, and can run five kilometres just for the fun of it.

"I can run, bike, play sports and have more fun without feeling sick afterward as a repercussion. I can concentrate better, too," says Oliver, who still must take anti-rejection medication, along with antibacterial meds and vitamins, and be tested for signs that he might be rejecting the kidney, which has been surgically attached in the front of his abdomen.

Oliver's surgical success story is just one of hundreds being written in the operating rooms of the Region's Pediatric Kidney Transplant Program, which, along with the Adult Kidney Transplant Program, is a part of Transplant Manitoba - Gift of Life.

As such, it provides insight, not only into the capricious nature of kidney disease, but also into the remarkable progress that has been made in the area of kidney transplants.

Since its inception in 1969, the Winnipeg-based program has transplanted more than 1,500 kidneys. Forty years ago, the one-year survival rate for a transplanted kidney was in the neighbourhood of 45 per cent, and the rejection rate was close to 80 per cent.

But since then, improvements in anti-rejection drugs, as well as advances in tissue typing, transplant surgery techniques and post-surgical monitoring have resulted in transplant survival rates reaching 90 per cent, while rejection rates have dropped to below 20 per cent.

Oliver Senger just months after receiving his father's kidney.

Oliver and thousands of patients like him are the beneficiaries of these and other improvements that have been pioneered or adopted by Transplant Manitoba. But while the program has a long record of achievement, officials say it now has the potential to help even more children and adults in need, thanks in large measure to a $4.6 million investment since 2005 that was designed to boost the number of kidney donations and transplant operations.

Dr. Peter Nickerson is Associate Dean (Research) for the University of Manitoba's Faculty of Medicine, the former head of Transplant Manitoba - Gift of Life, and the architect of the transplant investment plan. He says kidney disease is much more prevalent than many Manitobans realize, and the investment in the program was needed to keep pace with increasing demand for transplants.

In fact, the Manitoba Renal Program says this province has the highest rate of chronic kidney disease in Canada. Each year, more than 275 Manitobans start kidney dialysis treatment to stay alive, according to program officials. Based on world-wide population studies, it is estimated that as many as 100,000 Manitobans may be affected by chronic kidney disease in different stages.

To help answer the demand for care, Nickerson says the program today focuses on improvement in three key areas:

  • Increasing donation rates, either through living donations, or improving the deceased donor process, or by encouraging individuals to mark their organ donor card.
  • Improving allocation of donated kidneys. Manitoba was the first to make public the system by which available donor kidneys are allocated to those on the wait-list.
  • Pioneering research, especially in the area of organ rejection.

Nickerson says the main challenge facing the program is to increase kidney donations and boost the number of transplants performed. There are over 1,200 people on dialysis in Manitoba, with the rate of people being added to dialysis standing at six per cent per year. On average, 50 transplants are done a year, with 15 to 30 of those being kidneys from deceased donors. That could be increased two-fold, says Nickerson, who also serves as Executive Medical Director, Organs and Tissue Office, for Canadian Blood Services.

"We know that 90 to 95 per cent of the population support organ donation, but only 40 to 45 per cent of us have taken the step of signing a card or telling somebody," he says. "A second part of the problem is recognizing who can and cannot be a donor, so sometimes we miss an opportunity. The frequency that a physician in an ICU (intensive care unit) will encounter a potential donor is very low. Not everyone working in the ICU recognizes who can be a donor, so we do a lot of education in this area."

But things are improving. Five years ago, Manitoba had one of the lowest donation rates in Canada. But numbers have been increasing, thanks to the public and investment by Manitoba Health and the Winnipeg Health Region, which allowed Transplant Manitoba to educate health-care staff in recognizing potential donors. Last year, Manitoba had the highest donation rate in the country, at 15.4 deceased donors per million people.

In addition to receiving more organ donations, the program is also able to help a wider range of people, says Dr. David Rush, Medical Director of the Manitoba Renal Transplant Team.

"The quality of our compatibility assessment between donor and recipient has greatly improved in the past decade, along with improvements in the number and complexity of antirejection medications, which means the range of recipients for a donor kidney has broadened," he says. "Almost everything has changed since I arrived. Since 1982, medications have become more potent, stronger. We've introduced protocol biopsies and we are working on non-invasive ways to see how well the transplanted kidney is doing."

Another Manitoba first was making transparent to the public the rules governing how Transplant Manitoba allocates donated kidneys to recipients. With over 150 people on the waiting list for a transplant, and another 300 being worked up for the surgery, there's a lot of demand for kidneys that come from deceased donors. Consulting wait-list patients, Transplant Manitoba learned that they wanted to have a say in the rules and to have them made public. They also wanted a regular audit of the program's operations to ensure it was following the rules. The new rules have been in place since 2008 and are available to patients on the Transplant Manitoba website.

Oliver Senger just months after receiving his father's kidney.

Oliver Senger just months after receiving his father's kidney.

There are three principles that outline how patients are ranked on the recipient list: medical need, utility and justice.

At the top of the list are people who have urgent medical need, who can no longer get adequate dialysis and need a kidney in order to survive. Also at the top are people who are "highly sensitized." These individuals have many antibodies in their blood making it very difficult to find a compatible donor. Highly sensitized people make up about 30 per cent of the wait list. Yet they received less than five per cent of donated kidneys under the previous system.

"Those with high levels of sensitization react against almost all available kidneys from donors. This means only one donor in 100 could be a match for them. So if a compatible organ becomes available, and we don't give the highly sensitized person the kidney, they might never receive another offer," says Nickerson, who is also the Flynn Family Chair in Kidney Transplant Medicine at the University of Manitoba.

Children fall into the next highest category, along with people who have a perfect tissue match. Children rank highly because a transplant gives them the best opportunity to grow, develop and learn properly. Utility refers to how well the kidney can be matched between donor and recipient. The better the tissue match, the better the chance the transplant will last. Also, a kidney from a young donor can last for many years; therefore giving a young kidney to a young recipient maximizes the use of the donor's gift.

The third principle is justice, which means ensuring everyone who is on the waiting list for a transplant has a fair chance to receive an organ. Patients wanted to make sure that no one was disadvantaged by their age or ethnicity.

Has the new system achieved its goals? Are medically urgent or pediatric patients getting priority? Are disadvantaged patients, such as the highly sensitized, getting better access?

Yes, says Nickerson. The number of highly sensitized patients receiving a transplant has jumped to 12 per cent from three per cent, although they should be receiving closer to 30 per cent, as that's the proportion they make up on the wait list. Ethnic groups, Aboriginals and the elderly also receive transplants in proportion to their numbers on the wait list.

Pediatric patients, meanwhile, are dealt with at such speed that there are sometimes no children on the list.

Currently, there are 13 children being worked up for a transplant, and three are ready for the surgery, according to Julie Strong, Pediatric Transplant Co-ordinator with the Pediatric Kidney Program.

"One of the three has developed antibodies, because of a prior transplant that was rejected," says Strong, who co-ordinates the families of the children as they enter the program, in terms of education and getting the children ready for their transplant. This is a complicated process, as kids often need care from other specialists, including urology, cardiology, respiratory, growth and development along with psychiatry.

Transplants to children are a high priority because they tend to be more medically stable and generally do not suffer from other diseases, the way many adults do, making them prime candidates to thrive after a transplant.

"Children deserve the opportunity to fulfill their potential," says Dr. Patricia Birk, Medical Director of the Pediatric Kidney Program for Transplant Manitoba. "They also have excellent outcomes. From 2003 to 2011, we've seen a 90 per cent one-year graft survival rate when the child received a kidney from a living donor."

Children aren't affected by kidney disease in the same numbers as adults. Compared to 150 on the adult waiting list, there are less than 20 children waiting for a transplant. The numbers transplanted per year are also smaller, with 18 transplants done in 2007 and 15 in 2008.

"Children are affected by kidney disease due to congenital anomalies and inherited diseases," says Birk, adding that children must be over 10 kg in weight and two years of age before they can be considered for transplantation. Infants may be started on dialysis, and transplantation is held off until their small body has grown large enough to accommodate an adult-sized kidney.

The preference for children is to find a living donor, often a parent or another relative. A living kidney has not gone through the trauma of brain death in a deceased donor, and has a greater ability to function better, for longer.

For Brent Senger, there was no question he would donate a kidney to his son.

"Oli needed a kidney and I could do without it. I'm just glad that it has worked out for the best and that my kidney is working for him," says Brent, adding that Oliver has nicknamed the kidney "K3," like it was a pet akin to the family Malamutes, Nanook and Sitka.

A kidney ready for transplant.

Arnie Senger says it was a hard day when her two "guys" went into surgery, one after another. Brent's kidney was removed early in the day and he was soon wheeled to the recovery room. Then it was Oliver's turn in the operating room, with surgery done by Dr. Joshua Koulack. A good family friend kept Arnie company at the hospital, while the other two Senger children, Alex and Lucy, stayed at the apartment the family had rented in the city. Alex kept busy by phoning progress reports to Brent's parents in Saskatchewan, and Arnie's parents, who live in Australia.

"I now have three healthy kids - a precious gift that is often unappreciated by those who have known no difference," says Arnie, who was tested as a donor but could not follow through due to being an incompatible blood type with Oliver. "I am so proud of Oli and the way he has accepted and embraced his health. There is never a complaint about taking his meds or drinking his water. If you saw him, you would never know he is a kidney kid. Oli is hoping to participate in the World Transplant Games in Switzerland next March in the ski races."

Beyond that, the future is fuzzy. There are many factors affecting whether Oliver's new kidney will function properly, including taking his anti-rejection medications daily, drinking four litres of water a day, good nutrition and a healthy lifestyle.

All in all, Oliver says he's very thankful his dad donated a kidney.

"I still have to travel to Winnipeg for biopsies and have frequent appointments and blood work here in Saskatchewan," says Oliver, who is now in Grade 9. "It is nice to have appointments close to home so that I don't have to travel as much. I will miss less school and music and sports by being home more."

Arnie says that as parents, they made a big effort to help Oliver understand what was happening and what would likely happen as his renal failure progressed. They talked freely with him about his health and never kept any information from him or their other two children.

"I think this helped him be prepared for transplant. Oli certainly accepted every step of his renal failure and transplant with grace. He was given the opportunity to make a choice about his health care whenever there was a choice to make. We provided him with the information, pros and cons, and encouraged him to make the best decision," she says.

While most kidneys for transplant have traditonally come from deceased or living donors, such as a family member, efforts are being made to broaden the number of potential organ contributors.

For example, the Living Donor Paired Exchange is a country-wide program that co-ordinates living kidney donations between patients with a willing but incompatible donor and another pair in the same situation. It is a partnership between Canadian Blood Services and transplant programs across the country, and was launched in January 2009. Since its inception, more than 185 pairs have registered, including 20 altruistic donors who have no relatives they need to find a kidney for.

"The Canadian Blood Services is trying to set up a national registry for highly sensitized patients as well, so that if a kidney becomes available anywhere in the country that is a match for a patient, they would get that kidney," says Nickerson, adding that this registry should be launched in 2012.

The true value of the kidney transplant program is that it saves lives, and also saves money. By spending money hiring more surgeons and other staff, the medical side is ready to perform more transplants. Since 2006, following the increased investment by Manitoba Health and the Winnipeg Health Region in Transplant Manitoba, more than $1.2 million has been saved through transplants, money that would have otherwise been spent on dialysis therapy for these patients.

A kidney ready for transplant.

A kidney ready for transplant.

Nickerson notes that while transplants are one aspect of the spectrum, with a perfectly healthy person at one end, and a person with end-stage kidney disease at the other, stopping kidney disease from starting in the first place should be a priority for everyone.

While kidney disease may strike in childhood as an inherited disorder, many contract the disease in adulthood. All adults should undergo kidney disease screening, along with diabetes screening, including keeping an eye on their blood pressure, exercising and eating a healthy diet.

"Your best bet is to decrease your chances through early detection and positive changes in your lifestyle," he says.

Susie Strachan is a communications advisor with the Winnipeg Health Region.



Improving the odds: Winnipeg researchers help redefine standards of kidney transplant care around the world

The Winnipeg Health Region's kidney transplant program is quietly making a name for itself. In addition to providing a high level of care to transplant patients here in the city, it is also helping to redefine standards of care around the world.

Launched in 1969, the transplant program currently operates under the umbrella of Transplant Manitoba - Gift of Life, which is responsible for co-ordinating organ donations and transplant operations in the province.

Over the years, researchers working through the Region and the University of Manitoba's Faculty of Medicine have been involved in dozens of projects aimed at improving the transplant process. "Winnipeg is well-respected on the international kidney transplant science scene for coming up with new ideas to solve problems," says Dr. David Rush, Medical Director of the Manitoba Renal Transplant team at the Health Sciences Centre.

In one case, for example, researchers implemented a test to better determine whether a recipient would be a good match for a donated kidney. In another, researchers pioneered a method of monitoring the performance of a newly transplanted kidney.

The work is important. Generally speaking, transplants are successful if a donated kidney is a good genetic match for a donor. But even in these cases, an implanted kidney can trigger an immune response from the recipient's body, which can lead to the organ being rejected. In order to ensure a good match between organ donor and recipient, the first transplants in the 1960s involved only identical twins. In time, the risk of rejection was reduced through the use of drugs that controlled the immune system.

"In 1965, the one-year graft (transplant) survival rate was 45 per cent and rejection rates stood at 80 per cent," says Dr. Peter Nickerson, Associate Dean (Research) for the U of M's Faculty of Medicine and a former Director of Transplant Manitoba - Gift of Life. "By the 1980s, when we started using Cyclosporin, patients had an 85 per cent one-year graft survival rate and only a 40 per cent rejection rate. With the newer drugs used today, we have over 90 per cent one-year survival rates and rejection rates have come down to less than 20 per cent. Most people say it's because the drugs have improved."

But there was still a problem bothering Manitoba researchers. Before 2000, they lost about 10 per cent of the transplants within a couple of weeks of the operation. Researchers wanted to know why, so they investigated whether a more sensitive compatibility test to match donor organ to recipient would have prevented this early graft loss.

The standard test at the time involved mixing cells from the donor with serum from the recipient in a tube, and waiting to see if the serum killed the cells. If that happened, it meant the person had antibodies against the potential kidney donor, and that a transplant would not be compatible.

"When we saw we were losing 10 per cent of grafts early, we did a study to evaluate whether flow cross-matching would have detected lower levels of antibodies in the recipient's serum - that were being missed with the standard cross-match assay - that were causing this early graft loss," says Nickerson. Flow crossmatching was not routinely used in Canada at the time, and was being done by only a few centres in the United States.

"We received a grant from the Kidney Foundation, Manitoba Branch, to buy a flow cytometer for $120,000," says Nickerson. "We bought that in 1999, and we did our study and found that we would have picked up more positive crossmatches and avoided those transplants that had led to early graft loss.

"In 2000, we were the first centre in the country to implement flow cross-matching as the standard of care. We saw that by doing so, at six months, the graft survival rate went from 90 to 99 per cent."

In 2004, a national forum was hosted by the Canadian Council for Transplant and Donation, at which point, all provinces agreed to move to flow cross-matching.

"We now know ahead of time whether the recipient's immune system would aggressively reject the donated kidney," says Rush, who has been involved in research projects dating back to the 1980s. "That missing 10 per cent has dropped off radically, thanks to this more sensitive test."

Another Winnipeg first was the introduction of "protocol biopsies." This approach, developed by Rush 20 years ago, involves taking small tissue samples from the kidney at various intervals following a transplant to see how well it is performing. "We had a case where a recipient had received a kidney from a relative. There was one problem, at the one-year point. We did a biopsy and found the kidney was almost completely destroyed," says Rush. "We reasoned there had been a lot going on silently in that transplant that we were unaware of."

Further research determined that onethird of transplants were being rejected without any warning signs. "We coined the term ‘sub-clinical rejection' for this," says Rush, who is also a professor of internal medicine at the U of M's Faculty of Medicine.

Because children receive large adultsized kidneys which can conceal the signs of rejection, Dr. Patricia Birk, Medical Director of the Pediatric Kidney Program, has incorporated protocol biopsies into the clinical care of children with kidney transplants.

The Winnipeg approach was initially seen as unusual, but the technique eventually caught on around the world, especially during the 1980s and 1990s. Since then, advances in immunosuppression drugs have resulted in the technique being used with high-risk patients or those who are being weaned off immunosuppression drugs.

The quality of research taking place here was recognized in 2003, when Winnipeg was invited to participate in a series of projects funded by the U.S.-based National Institutes of Health (NIH).

In one project, local researchers, led by Nickerson, joined with others at Mt. Sinai in New York City, Cleveland Clinic, Yale University, and Emory University in Atlanta. The objective was to determine whether a non-invasive test could be developed to serve as a substitute for a protocol biopsy, which involves sticking a needle into a kidney. Diagnostic Services of Manitoba became the core lab for pathology in the study, Dr. Ian Gibson became the central pathologist, and the local transplant immunology laboratory became the core lab studying antibodies.

That project has determined that some immunological tests may be helpful, and the group is now in phase two of the study, which involves determining whether a particular anti-rejection drug - which is beneficial in the short-term, but potentially harmful in the longer term - can be safely withdrawn from the immunosuppression protocol.

Meanwhile, Rush is working with the National Research Council on another NIH-funded project. This one involves using magnetic resonance spectroscopy (MRS) to check for early warning signs of kidney failure. This process essentially involves putting urine on a magnet and looking for metabolites that might provide clues. Dr. Tom Blydt-Hansen is working on a similar project for the pediatric program.

"At the moment, nobody has a test that will tell them, non-invasively, what is going on in the kidney," says Rush. But the MRS test is showing promise. "We're seeing good results 90 per cent of the time, and are working to perfect the technique," he says. The project - the largest renal transplant study ever done - includes patients and researchers from several American institutions, including the Mayo Clinic, as well as University of Alberta Hospital in Edmonton.





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