The role of peroxisome proliferator activated receptor gamma in sodium transport in human proximal tubule cells

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Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the definitive cause of fluid retention with the use of PPAR gamma agonists is not known. Studies reported in the last 12 - 18 months have suggested that a common pathway may be involved in the development of the fluid retention, the high blood pressure and the scarring that occurs in the kidney. This project will be the first to provide a comprehensive examination of the effect of PPARgamma induction on renal sodium absorption and fluid retention in the human proximal tubule cells and the potential molecular mechanisms underlying them. This will provide insight as to potential adjuvant treatments for patients with diabetes.