Grant: Operating Grant

The kidney is an important physiological "filter" that allows us to eliminate all waste products, while retaining vital components. One vital molecule is bicarbonate, which we must retain to compensate for the acid produced while processing food. The kidney anion exchanger 1 (kAE1), which exchanges chloride for bicarbonate, is of particular importance for bicarbonate reabsorption. Some individuals with mutated bicarbonate transporter kAE1 are unable to properly retain bicarbonate in their kidneys, thus bicarbonate is expelled instead of reabsorbed. As a result, these patients have an acidic plasma, produce kidney stones and failure to thrive. Furthermore, these patients lose salt in their urine, via an unknown mechanism. Our goals are not only to understand why and how these patients become acidotic but also to unveil the molecular links between abnormal bicarbonate reabsorption, development of kidney stones and loss of salt in the urine. The result of our studies will be relevant to the growing population of patients with kidney stones as well as hypertensive Canadians, a condition that affects more than a third of North American adults. To reach these goals, we will use an animal model mimicking the pathology seen in these patients, complemented with in vitro analyses to dissect these mechanisms at the cellular level. These two levels of investigation will allow us to obtain a global and complete picture of this pathology, thereby providing leads towards development of new therapeutic drugs.