Long-Term Regulation of Renal Urea Transporters during Antidiuresis

Abstract

To produce a concentrated urine, the renal medulla needs hypertonicity for the reabsorption of free water from collecting duct. The single effect that increases interstitial tonicity in the outer medulla is the active NaCl reabsorption in the thick ascending limb, while the single effect in the inner medulla is the passive efflux of NaCl through the thin ascending limb. The passive mechanism in the inner medulla requires high interstitial urea concentration. Two main groups of urea transporters (UT-A, UT-B) are present in the kidney, which maintains the high concentration of urea in the deepest portion of the inner medulla by intra-renal urea recycling. Recent studies suggest that UT-A1 in the terminal inner medullary collecting duct is up-regulated when urine or inner medullary interstitial urea is depleted in order to enhance the reabsorption of urea, while UT-A2 in the descending thin limb of loops of Henle and UT-B in the descending vasa recta are increased when outer medullary interstitial urea concentration is high, in order to prevent the loss of urea from the medulla to the systemic circulation, thereby increasing intra-renal urea recycling. This review will summarize the functions of the renal urea transporters in urine concentration mechanism and the recent knowledge about their long-term regulation.

Keywords: Urea; Urea transporters; Urine concentration; Water.

Fig. 1

The location of urea transporters and the intra-renal urea recycling. UT, urea transporters; AQP, aquaporin (modified from Ref. 26 with permission). NaCl is actively transported out from thick ascending limb in the outer medulla, while passively transported out from thin ascending limb in the inner medulla. The passive transport of NaCl in the inner medulla requires high concentration of urea in the inner medullary interstitium, which is maintained by urea transporters that mediate intra-renal recycling of urea. The efflux of NaCl from both thick and thin ascending limb increases medullary interstitial tonicity and then water is reabsorbed from collecting duct through AQP 2-4 water channels.