Sodium reabsorption is finely tuned in the distal portion of the nephron by the sodium-chloride cotransporter (NCC) in the distal convoluted tubule and the epithelial sodium channel (ENaC) in the collecting duct. Although only 5-10% of filtered urinary sodium typically reaches these portions of the nephron, this represents roughly 15-times the average daily dietary sodium intake. Nearly 100% of sodium is reabsorbed in the setting of sodium depletion, hypovolemia, or certain pathogenic conditions (congestive heart failure, decompensated cirrhosis). The aldosterone-sensitive collecting duct is largely responsible for this fine regulation by its ability to maximally active ENaC-dependent sodium reabsorption. Although ENaC activity and expression can be measured in vitro (patch clamp) and animal studies (micropuncture, Western blot), assessment in clinical studies is very limited due to the inability to access adequate tissue. Therefore, investigators have used the urinary sodium/potassium ratio as an index of ENaC activity. The study team has recently developed a mass spectrometric assay for urinary exosomal epithelial sodium channel (γENaC), demonstrating a 15-fold increase during low sodium diet or during aldosterone administration. This method represents a significant technical advance and provides clinical investigators a tool to measure ENaC expression in future clinical studies. The study team anticipates that a similar approach will enable clinicians to measure the expression of additional relevant transporters and channels.