INNOVATOR

Distinguished Researcher Dr. Todd Alexander has been granted $750,000 over five years from the Foundation, through the Women and Children’s Health Research Institute, to take his research to the next level.

UNDERSTANDING THE CAUSE

Dr. Todd Alexander is finding answers to many of the questions surrounding childhood kidney disease BY ELIZABETH CHORNEY-BOOTH

Our kidneys are vital and complicated organs, but few of us give them a lot of thought unless they start to pose a problem. While it’s not as widespread as some other pediatric medical issues, childhood kidney disease can be devastating to patients and their families, causing growth delays, bleeding abnormalities and, all too often, premature death. Treatment for childhood kidney disease commonly involves a fairly intense drug and dietary regimen that can greatly affect a child’s quality of life.

Dr. Todd Alexander wants to improve the outcomes and decrease the burden of treatment for families affected by childhood kidney disease. In Alexander’s opinion, the best way to do that is to better understand what causes the disease in the first place. In comparison to diseases like cancer or heart disease, relatively little research has been done with kidney disease, leaving a lot of questions unanswered. Since many of the symptoms of kidney disease, such as proteins in the urine or increased blood pressure, often go unnoticed, researchers have trouble studying patients who are in the early stages of kidney disease in particular.

As part of the University of Alberta’s Women and Children’s Health Research Institute’s Distinguished Researchers program within the Stollery Science Lab, Alexander is examining kidney disease at a molecular level to figure out why a child’s kidneys may become diseased and even fail at such an early age. Thanks to funding from the Stollery Children’s Hospital Foundation’s donors, Alexander and his team have been granted $750,000 over five years to follow this line of research.

“[Essentially], we want to be able to give families an explanation as to why

DID YOU KNOW? Halting the progression of childhood kidney disease is important — Dr. Alexander has already published data that shows that a third of children diagnosed with kidney failure before the age of two do not survive long enough to receive a kidney transplant. The survival rates are better for older children, but preventing the progression of their disease early on can reduce the need for dialysis or transplants.

their child is sick,” Alexander says.

A big part of Alexander’s research focuses on the way phosphates are absorbed (or, in the case of many patients, not properly excreted) by the body. Patients that have an abnormally high level of phosphates in their blood can experience renal failure and heart disease if they don’t take heavy doses of pills every day. While researchers have known about a link between phosphates and diseased kidneys for some time, Alexander is working to better understand what make phosphate levels worse in patients with kidney disease and how he can more effectively lower those levels to prevent the progression of that kidney disease or other ailments like the weakening of bones or cardiovascular disease.

“At the simplest level, I’m looking at ways to manipulate phosphates to prevent the progression of kidney disease,” Alexander says. “I want to make patients’ lives better so that instead of taking 12 tablets a day they can take two. The goal would be to give them medicine to prevent phosphates being absorbed into the blood from the intestine and to specifically block the pathway by which phosphates are absorbed.”

Regulating those phosphate levels is just one element of Alexander’s research. As he explains it, kids with kidney disease are not able to pee out

the phosphates because their kidneys are sick, so he is trying to get to the root cause of this and determine how to manipulate absorption from the intestine. Other parts of Alexander’s research involve looking at DNA sequences to determine how abnormal genes may play a part in kidney disease and other related disorders — he has found that the majority of pediatric kidney disease can be attributed to genetics.

Naturally, Alexander is not working alone: he has nine people in his lab in Edmonton and is also collaborating with academics in the United States and Europe, as well as American and French drug companies. Albertans are incredibly fortunate to have such an innovative expert doing research and treating kids right here in the province. Like the work of other Distinguished Researcher grant recipients, Alexander’s efforts are providing inspiration and hope to both fellow researchers and local patients.

“We’re really lucky to have some of the best researchers for pediatric care anywhere right here in Edmonton, including Dr. Alexander, who is elevating care right in our own backyard and across the globe,” says Mike House, president and CEO of the Stollery Children’s Hospital Foundation. “What excites us is the knowledge that we can transform children’s health together.”

Alexander’s hope is that his research will lead to therapies not only for the children in Alberta who need transplants and dialysis each year, but that he’ll also be able to help kids with less severe kidney disease as well as other disorders that are not obviously related to the kidneys but can be linked with excessive phosphate in the blood.

“[Further research] and understanding brings a hope,” he says, “because when we know what’s happening we can make more intelligent treatment decisions that will prevent progression and kidney failure.”

Beyond Kidney Disease

WHEN DELORES CRAN

DALL’S now 14-year-old daughter Cadence was nine, Crandall took her to the doctor for what she thought was an injury sustained during a softball game. Crandall, who lives with her family on a farm near Wetaskiwin, was shocked to learn that Cadence had developed a case of genetic rickets, a disease that softens and weakens the bones. Given that rickets usually affects much younger children and Cadence didn’t present any of the risk factors usually associated with the disease, doctors couldn’t figure out why she had become so ill. Her growth ground to a halt, she had to give up many of the sports and activities she loved, and she required a wheelchair if her parents took her on a trip to the mall.

Even though rickets isn’t generally related to kidney disease, a high level of phosphates in her system led Cadence to Dr. Alexander’s office. The family had also sought the opinions of doctors in Ontario and at the Mayo Clinic in the United States, but it was Alexander who did the genetic research. As he puts it, he and the other doctors “worked together to be convinced [Cadence’s condition] was genetic, and we identified a presumed cause for her disease.”

Cadence was put on a new drug therapy last summer — after a team of doctors including Alexander appealed to the drug manufacturer to supply the drug on a compassionate-use basis — and has seen a drastic improvement. She’s grown substantially and is even horseback riding again, restoring the sense of independence and freedom that her illness took away. Crandall credits Alexander’s perseverance for changing her daughter’s life.

“Dr. Alexander and his team have given her back her life,” Crandall says. “Even though her kidneys weren’t the issue, he continued to see us and continued to be her champion. He just cared for us.”