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

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Abstract

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.

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Fig. 1
Fig. 2
Fig. 3

Modified from Wei et al. (2015), with permission

Fig. 4

Modified from Pannabecker (2013), with permission

Fig. 5

Reproduced from Issaian et al. (2012), with permission

Fig. 6
Fig. 7
Fig. 8

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Abbreviations

AQP:

Aquaporin

AMPK:

Adenosine monophosphate kinase

ATL:

Ascending thin limb

AVP:

Arginine vasopressin

AVR:

Ascending vasa recta

CD:

Collecting duct

dDAVP:

Desmopressin

DTL:

Descending thin limb

DVR:

Descending vasa recta

Epac:

Exchange protein activated by cAMP

IM:

Inner medulla

IMCD:

Inner medullary collecting duct

ISOM:

Inner stripe of the outer medulla

LXR:

Liver X receptor

NHE3:

Na+/H+ exchanger 3

NKCC2:

Na+–K+–2Cl− cotransporter 2

OM:

Outer medulla

OSOM:

Outer stripe of the outer medulla

P2Y12-R:

Purinergic P2Y12 receptor

PGE2 :

Prostaglandin E2

PRR:

Prorenin receptor

sPRR:

Soluble prorenin receptor

STZ:

Streptozotocin

TAL:

Thick ascending limb

UT:

Urea transporter

V2R:

Arginine vasopressin receptor 2

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Acknowledgements

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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  1. Department of Physiology, Banner University Medical Center, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ, 85724-5051, USA

    C. Michele Nawata & Thomas L. Pannabecker

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Correspondence to C. Michele Nawata.

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Nawata, C.M., Pannabecker, T.L. Mammalian urine concentration: a review of renal medullary architecture and membrane transporters. J Comp Physiol B 188, 899–918 (2018). https://doi.org/10.1007/s00360-018-1164-3

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