Project 176752

Both kidney stone formation and osteoporosis are diseases characterized by increased urinary excretion of calcium. Unfortunately, to date, why certain individuals waste calcium is not known. These studies seek to understand this. The proposed research is specifically aimed at understanding how calcium, once filtered by the glomerulus (individual kidney filter), is reabsorbed back into the proximal tubule. This part of the nephron (single kidney tubule) was chosen as it is where the greatest amount (>60%)of calcium is absorbed from. Previous studies have implicated sodium reabsorption in this process. However, whether the molecular determinants of sodium absorption, mediate calcium absorption has not been directly tested. This will be done both in a tissue culture model of proximal tubular cells and in knockout mice. A sodium transport protein, the epithelial sodium proton exchanger, NHE3, is central to proximal tubular sodium absorption. Therefore its role in calcium reabsorption will be delineated. First in cell culture models, then in NHE3 knockout mice. The latter studies will look for the effects of calcium wasting on the whole animal. Together the proposed research will delineate molecular details of renal calcium regulation and consequently provide insight into renal calcium wasting and its consequences,kidney stones and osteoporosis.