The Kidney Foundation of Canada

Dr. Indra Gupta 

Dr. Indra Gupta

McGill University Health Centre Research Institute, QC

Claudin function in kidney development and in disease

Co-applicant(s): Aimee K. Ryan; Sero Andonian

2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Urology

Lay Summary

The incidence of kidney stones is on the rise and studies in Canada estimate that 1 in 10 adults may be affected. In addition to the acute severe pain caused by the stone, in the long-term kidney stones can contribute to chronic kidney disease in children and adults. Unfortunately, treatment options for stones are extremely limited. New, individualized treatment strategies are needed. Kidney stone development is impacted by dietary salt intake and regulation of salt levels in blood and urine. Salt is absorbed from the intestine into the blood. It then passes from the blood into the kidney, where salt balance is controlled by hundreds of thousands of filtering units called nephrons. In the nephron, some salt is reabsorbed back into the circulation to maintain the correct balance in the blood. Too little salt reabsorption leads to excessive salt in the urine, which forms crystals that develop into kidney stones.

Claudin proteins regulate the barriers that control the movement of salt between the nephron and the blood; some make the barrier tighter and others make it leakier. Individuals within the population can have different versions of each claudin, which when combined determine their “claudin genetic signature”. We will perform studies to determine the correlation between different claudin signatures and the propensity to develop kidney stones and ultimately chronic kidney disease. We will create a diagnostic tool to assess claudin signatures to determine if this will predict who will get kidney stones repeatedly. Finally, we will test a novel claudin-targeted treatment using the leaf of a plant known as Bryophyllum pinnatum that regulates claudin barrier function in the nephron. We will give tablets with the leaf contents or a placebo and determine if patients have less salt in their urine, suggesting a lower risk of having a kidney stone.