Grant: Project Grant

Kidneys in our bodies regulate how much and which waste products are eliminated in the urine. Key cells in this process are called intercalated cells, which regulate blood acid-base balance and urinary acidification. Defects in these cells caused by mutations of the kidney anion exchanger 1 (kAE1) result in distal renal tubular acidosis (dRTA), a disease where patients experience an acidic blood, kidney stones, increased risk of kidney failure, and urinary loss of salts. Studying the mechanisms of this disease is therefore important as it may identify new therapeutic targets relevant to the millions of Canadians who suffer from chronic kidney disease. Our preliminary results show that kAE1 interacts with another protein called claudin-4, and that altering one or the other results in the disease symptoms. In this funding period, we will dissect the relationship between these 2 proteins, verify our findings in vivo and alter their functional and physical interaction using drugs or genetic engineering as a lead towards development of therapeutic approaches to not only treat dRTA patients but also patients with chronic kidney disease.