Unlocking the mysteries of biology
A fundamental question about calcium reabsorption in the kidney is finally answered
In a time when just about anything you could ever want to know is a Google search away, it’s hard to imagine that some of the most delicate processes of the human body remain mysteries to science.
Todd Alexander, a pediatric nephrologist, Stollery Science Lab Distinguished Researcher and professor in the Department of Pediatrics, has recently cleared out at least one of human biology’s unknowns. After 10 years of searching for answers, his team has unlocked a vital piece of information about how our kidneys reabsorb calcium back into our blood, enabling the mineralization of our bones—and it could be big news for people living with osteoporosis and kidney stones.
Until this discovery, nobody really knew which proteins—a constellation of amino acids constituting the building blocks of our cells—were involved in the majority of calcium reabsorption in our kidneys. This means there hasn’t been a good target for developing treatments for people who suffer from faulty calcium reabsorption: people with osteoporosis, who don’t deposit enough calcium into their bones, or people with kidney stones, who don’t absorb enough calcium through the millions of tiny tubules that make up their renal system.
The Alexander lab, however, pinpointed two proteins, called claudin-2 and claudin-12, as the essential players in regulating calcium reabsorption. Without these proteins, the cells lining someone’s intestines and kidneys can’t form proper pores to channel calcium back into the blood where the body needs it most.
“To me, that’s exciting,” Alexander says. “We know that people with osteoporosis and people with kidney stones are unable to hold onto calcium, so they waste it in their urine. Now we know how that occurs—it gives us the information to make it work better, so they stop wasting calcium.”
You might think these conditions affect only adults, but children can also develop osteoporosis and kidney stones.
“Juvenile osteoporosis is a serious issue as it develops when a child is building their bone strength,” he says. “By the time you’re 18, you’ve built about 90 per cent of your bone mass, and losing any mass during these critical bone-building years can put you at risk for complications like fractures.”
And children born prematurely or with a health condition—like diabetes—are at increased risk for kidney stones.
In November 2021, Alexander’s team published their findings in the prestigious Proceedings of the National Academy of Sciences, one of the most cited scientific journals in the world. Publishing in a journal this large isn’t just for bragging rights. It means scientists around the globe will be exposed to this new, fundamental piece of knowledge about the body—a crucial target to zero in on when developing treatments and improving the health of people struggling with calcium wasting disorders.
"It took a village, and a whole decade, to identify the specific proteins that facilitate protein absorption."
But the discovery, Alexander says, also speaks to the reality of scientific research. The finding was only made possible, he says, through the work of dozens of researchers and the essential funding through 19 grants and studentships from the Stollery Children's Hospital Foundation. It took a village, and a whole decade, to identify the specific proteins that facilitate protein absorption.
“It’s like a marriage—it’s a long-term commitment,” Alexander says. “You have a question and you want an answer. If you think it’s an important question, you’ll keep pursuing it until you get an answer.”
Getting real answers about the human body takes a lot more than a single scientist working alone at their bench, a lightbulb going off above their head. The most impactful discoveries are built upon years of work and research networks.
It’s all too relevant in light of the Women and Children’s Health Research Institute’s 15-year anniversary and the connections and support such an institute makes possible—vital in the long, but necessary, road of research, says Alexander, who is also the Institute’s associate director.
“There are highs where you figure something out and then you write a paper, it gets peer-reviewed, it gets published, and now the world knows what you know,” Alexander says. “Then, there are times where your hypothesis is incorrect and you have to go back to the drawing board. But that’s just science. That’s what you signed on for when you took the job.”
Todd Alexander is supported by the Stollery Children’s Hospital Foundation through WCHRI.