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Award-Winning Pharmacology and Toxicology Research: Does Lead Exposure Lead to Kidney Stones?

  • In 2018, Assistant Professor of Pharmacology and Toxicology, Greg Landry, PhD, DABT received the New Investigator Award from the American Association of Colleges of Pharmacy for his research on the correlation between lead exposure and kidney stone formation. His research continues.

    Assistant Professor of Pharmacology and Toxicology, Greg Landry, PhD, DABT, was one of just sixteen researchers nationwide honored by the American Association of Colleges of Pharmacy (AACP) in 2018 with the New Investigator Award for his research proposal, “Effects of Lead on Oxalate Nephrolithiasis.” His research aims to uncover the reason for the correlation between increased lead exposure and increased kidney stone formation. More specifically, Dr. Landry wants to learn whether chronic lead exposure increases the concentration of calcium in the kidneys, which in turn increases the risk of kidney stone formation.

    Although the makeup of kidney stones is known to be 75-80% calcium oxalate (minerals that clump into crystals or stone-like structures), the mechanism behind this formation is not yet understood. One hypothesis suggests that oxalate levels dictate stone formation, whereas another suggests that calcium levels are the determinant. Currently, the literature supports the calcium hypothesis. One reason for this is that people with higher amounts of calcium in their system have a greater chance of forming stones. The calcium hypothesis holds that the urine becomes super-saturated with calcium, which then combines with oxalate to form the insoluble precipitate known as the kidney stone. On the other hand, the calcium hypothesis is made problematic by the “kidney stone belt,” a geographical area covering the hot southeastern region of the United States. Based on the geographic distribution, it is possible that hydration may play a cause in the formation of kidney stones.

    Dr. Landry’s research is aimed at another possible environmental cause: chronic heavy metal exposure. “I reached this hypothesis because we already know that lead can release calcium from its intracellular stores,” he says. To study this, Dr. Landry dissects the kidney formation of transgenic fruit flies that lack specific calcium receptors called IP3 receptors. “Normally, IP3 binds to its receptor and causes an increase in calcium release,” Dr. Landry explains. “However, lead molecules can activate this receptor as well, causing the same calcium release.”

    The literature already accepts the notion that lead exposure raises the risk of kidney stones, but the exact mechanism behind it remains a mystery. Dr. Landry hopes to answer this question by breeding transgenic fruit flies lacking in the IP3 receptor. If his results show a decrease in calcium oxalate crystal formation, it will indicate that IP3 receptors are indeed a factor in kidney stone formation and may elucidate the way the mechanism works.

    If Dr. Landry’s hypothesis is proven correct, it could bring an increased understanding of idiopathic kidney stone formation. It would also mean that people could take measures to prevent kidney stones, by decreasing their exposure to lead—something people living in old cities or apartments should take into consideration. Currently, one in eleven people will suffer from a kidney stone at some point in his or her life. In addition to sparing many from this condition and possible consequent hospital visits, Dr. Landry’s research could save billions of dollars in healthcare spending. According to Dr. Landry, “The cost burden on the healthcare system from kidney stones is commensurately enormous, exceeding ten billion dollars annually.”

    Dr. Landry has presented his preliminary results at the AACP’s annual meeting in Chicago, Illinois, and at the full faculty meeting on the MCPHS Worcester campus. He has recently submitted a paper on his research, which is ongoing and conducted with the help of graduate and undergraduate pharmacy students.

    In addition to preparation for a career in research, a degree in Pharmacology and Toxicology provides students with a robust foundation for medical school, veterinary school, as well as a wide range of graduate programs. The Bachelor of Science in Pharmacology and Toxicology program at MCPHS is one of just eight programs of its kind in the country.