Journal of Comparative Physiology B

, Volume 188, Issue 6, pp 899–918 | Cite as

Mammalian urine concentration: a review of renal medullary architecture and membrane transporters

  • C. Michele NawataEmail author
  • Thomas L. Pannabecker


Mammalian kidneys play an essential role in balancing internal water and salt concentrations. When water needs to be conserved, the renal medulla produces concentrated urine. Central to this process of urine concentration is an osmotic gradient that increases from the corticomedullary boundary to the inner medullary tip. How this gradient is generated and maintained has been the subject of study since the 1940s. While it is generally accepted that the outer medulla contributes to the gradient by means of an active process involving countercurrent multiplication, the source of the gradient in the inner medulla is unclear. The last two decades have witnessed advances in our understanding of the urine-concentrating mechanism. Details of medullary architecture and permeability properties of the tubules and vessels suggest that the functional and anatomic relationships of these structures may contribute to the osmotic gradient necessary to concentrate urine. Additionally, we are learning more about the membrane transporters involved and their regulatory mechanisms. The role of medullary architecture and membrane transporters in the mammalian urine-concentrating mechanism are the focus of this review.


Kidney Urea transporters Aquaporins Renal medulla 





Adenosine monophosphate kinase


Ascending thin limb


Arginine vasopressin


Ascending vasa recta


Collecting duct




Descending thin limb


Descending vasa recta


Exchange protein activated by cAMP


Inner medulla


Inner medullary collecting duct


Inner stripe of the outer medulla


Liver X receptor


Na+/H+ exchanger 3


Na+–K+–2Cl cotransporter 2


Outer medulla


Outer stripe of the outer medulla


Purinergic P2Y12 receptor


Prostaglandin E2


Prorenin receptor


Soluble prorenin receptor




Thick ascending limb


Urea transporter


Arginine vasopressin receptor 2



This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK083338, National Science Foundation Grant IOS-0952885 and Joint DMS/NIGMS Initiative under NSF Grant DMS-1263943.


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Authors and Affiliations

  1. 1.Department of Physiology, Banner University Medical CenterUniversity of ArizonaTucsonUSA

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