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Key features of altered renal function include altered fluid and salt accumulation and body weight. To address these functions mice mouse weight will be determined over time.  Body fat can be assessed using a small whole body NMR (Bruker Mini-spin).  Daily Na/K intake will be calculated from food intake and combined urinary and fecal (nitric acid extract) cation content.  Sodium avidity, will be assessed by measuring urine sodium and creatinine excretion during the first 24 hours after switching from low sodium (0.02%w/w) to high sodium 4% w/w; measurement of urine and plasma aldosterone.  We have used this approach to demonstrate differences in collecting duct function due to Cre mediated deletion of PPARγ from the collecting duct (23).

Publications for Sodium balance (1)

Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med (2005) 11:861-6
View abstract View in PubMed

Thiazolidinediones (TZDs) are widely used to treat type 2 diabetes mellitus; however, their use is complicated by systemic fluid retention. Along the nephron, the pharmacological target of TZDs, peroxisome proliferator-activated receptor-gamma (PPARgamma, encoded by Pparg), is most abundant in the collecting duct. Here we show that mice treated with TZDs experience early weight gain from increased total body water. Weight gain was blocked by the collecting duct-specific diuretic amiloride and was also prevented by deletion of Pparg from the collecting duct, using Pparg (flox/flox) mice. Deletion of collecting duct Pparg decreased renal Na(+) avidity and increased plasma aldosterone. Treating cultured collecting ducts with TZDs increased amiloride-sensitive Na(+) absorption and Scnn1g mRNA (encoding the epithelial Na(+) channel ENaCgamma) expression through a PPARgamma-dependent pathway. These studies identify Scnn1g as a PPARgamma target gene in the collecting duct. Activation of this pathway mediates fluid retention associated with TZDs, and suggests amiloride might provide a specific therapy.

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Last updated on 2007-02-06 Moderated by Jimmy Hao