Return of the secretory kidney

The evolution of the kidney has had a major role in the emigration of vertebrates from the sea onto dry land. The mammalian kidney has conserved to a remarkable extent many of the molecular and functional elements of primordial apocrine kidneys that regulate fluid balance and eliminate potentially toxic endogenous and xenobiotic molecules in the urine entirely by transepithelial secretion. However, these occult secretory processes in the proximal tubules and collecting ducts of mammalian kidneys have remained underappreciated in the last half of the twentieth century as investigators focused, to a large extent, on the mechanisms of glomerular filtration and tubule sodium chloride and fluid reabsorption. On the basis of evidence reviewed in this paper, we propose that transepithelial salt and fluid secretion mechanisms enable mammalian renal tubules to finely regulate extracellular fluid volume and composition day to day and maintain urine formation during the cessation of glomerular filtration.