Urinary concentration and dilution in the aging kidney

Abstract

Aged people and rats have a reduced ability to maximally concentrate their urine. Many of the key transport proteins that contribute to urine concentrating ability are reduced in the medulla of aged rats. The reductions in the abundances of water, sodium, and urea transport proteins, and their reduced response to water restriction, contributes to the reduced ability of aged rats to concentrate their urine and conserve water. If similar mechanisms occur in human kidneys, it would provide a molecular explanation for the reduced concentrating ability in aging and may provide opportunities for novel therapeutic approaches to improve urine concentrating ability.

1

Transport proteins involved in the urinary concentrating mechanism. In the outer medulla, active NaCl reabsorption via NKCC2/BSC1 in the thick ascending limb of the loop of Henle generates a hypertonic medullary interstitium. This concentrates NaCl in the lumen of the thin descending limb of the loop of Henle by osmotically removing water via AQP1 water channels. In the inner medulla, passive NaCl reabsorption exceeds urea secretion. Water is reabsorbed from the collecting duct, in the presence of vasopressin via AQP2 in the apical plasma membrane and AQP3 and AQP4 in the basolateral plasma membrane. Urea is concentrated in the collecting duct lumen until the fluid reaches the urea-permeable terminal inner medullary collecting duct where urea is reabsorbed into the inner medullary interstitium via the UT-A1 and UT-A3 urea transporters.

2

Water restriction does not increase AQP2 protein abundance in 30 or 15 month-old rats. Panel A: densitometic summary. There was no significant difference between hydrated (Hyd.) vs. dehydrated (Dehyd) in the 30 or 15 month-old rats. Asterisk indicates a significant difference between hydrated (Hyd.) vs. dehydrated (Dehyd) 4 month-old rats. Panel B: western blot showing that AQP2 protein (a non-glycosylated 29 kDa band and a glycosylated smear from 35−45 kDa) abundance is not different between hydrated (h) and dehydrated (D) 30 month-old rats but is increased significantly increased in dehydrated (D) vs. hydrated (H) 4 month-old rats. Data from references [23;24].

3

Urea transporters are reduced in 30 month-old rats compared to 10 month-old rats. Panel A: UT-A1 protein abundance. Panel B: UT-B protein abundance. Panel C: UT-A3 protein abundance. Asterisk indicates a significant difference between 30 and 10 month-old rats. Data from references [21;43].