We propose that the necessary increase in growth and function of the renal tubular system may be a critical precursor to development of hypertension in those with a nephron deficit. Although mammalian renal organogenesis (i.e. formation of nephrons) is completed either prior to birth (humans, sheep, spiny mouse, baboons) or soon after birth (rats, mice, dogs),
nephrons continue to mature with respect to both size and function in the postnatal period. Changes in function such as GFR, renal blood flow, mean arterial pressure and tubular reabsorption of sodium all occur very early in childhood (within a few hours to days after birth). However, the postnatal growth of the kidney occurs over a longer Pexidartinib supplier period of time and is marked by a significant increase in size of both the glomerulus and the renal tubular system. Significant maturation of tubular reabsorption of sodium and growth of tubules occurs in the postnatal period. Lumbers et al. demonstrated that fractional reabsorption of sodium in the proximal segments was significantly less in fetal compared with adult sheep and this resulted in a greater delivery
of sodium to the distal segments and also greater reabsorption of sodium via the distal tubules. However, in the adult, the proximal tubules are the major site for reabsorption of sodium. This increase in reabsorption of sodium in the proximal tubules in the adult is due to significant growth of the proximal tubules. CHIR-99021 supplier In the human, the proximal tubules see more have been shown to increase in size by as much as 12-fold between birth to an age of 18.
Similarly, in the rat, size of the proximal tubule has been shown to increase linearly between birth and a postnatal age of 40 days due to increased length, diameter and surface area of the tubular apical and basolateral membranes.[17, 18] In humans and other mammals, growth of all segments of the tubules in the postnatal period is also characterized by a significant increase in expression of mitochondria to provide ATP for the energy dependent Na+K+ATPases, increased expression of Na+K+ATPases on the basolateral membrane to actively transport sodium out of the tubules, and increased expression of the Na+/H + exchanger and amiloride sensitive epithelial sodium channels (ENaC) on the apical membrane which mediate entry of sodium into the tubular epithelium from the lumen.[17, 18, 20] These adaptations in structure and function of the renal tubules are necessary to deal with the increase in filtered load of sodium associated with the marked increase in GFR that occurs between the pre- and postnatal periods. In term human babies, GFR increases rapidly over the first two weeks of life and then steadily until the age of two. This increase in GFR, in part, is associated with hypertrophy of glomeruli. Fetterman et al.