Grant: Operating Grant

One in ten Canadians will pass a kidney stone in their lifetime. Passing a stone is painful and the numerous Emergency and Operating Room visits required for treatment is expensive. Moreover, emerging evidence from my research program and others has identified an increased risk of chronic kidney disease, dialysis and heart disease in people with kidney stones. The risk is greatest for women under the age of 50. Therapies aimed at preventing and/or dissolving kidney stones already present in the kidney are lacking. The main therapy is to increase water ingestion and decrease sodium intake. In some individuals a water pill can be used, but it is poorly effective and has significant side effects. The main risk factor for developing kidney stones is having urine with a high calcium content. A large majority of people with kidney stones display this attribute. We do not know why this is. The purpose of the proposed research is to try and understand why and how people excrete too much calcium in their urine. We know that sodium intake increases calcium excretion in normal people and people with kidney stones. Our work will identify molecules and pathways responsible for this association such that new therapies can be developed targeting this pathway. We have recently described a novel pathway in the kidney whereby higher levels of calcium in the blood cause increased calcium excretion in the urine in normal people. Our research will identify all the molecules in this pathway, so that drugs targeting it can be generated. Finally, we have found a genetic alteration in a gene central to this latter pathway in people who form kidney stones. We wish to understand how this mutation affects calcium excretion in these kidney stone formers such that specific therapies can be designed for them. Together, these studies will delineate molecules and mechanisms that increase urinary calcium excretion, providing novel targets for much needed new kidney stone therapies