2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006101108v1 18/3/679    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fenton, R. A. Articles by Knepper, M. A. Search for Related Content PubMed PubMed Citation Articles by Fenton, R. A. Articles by Knepper, M. A. Related Collections Related Articles

Urea and Renal Function in the 21st Century: Insights from Knockout Mice

Robert A. Fenton^* and Mark A. Knepper

^* Water and Salt Research Center, Institute of Anatomy, University of Aarhus, Aarhus, Denmark; and Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institutes, National Institutes of Health, Bethesda, Maryland

Address correspondence to: Dr. Robert A. Fenton, Water and Salt Research Center, Institute of Anatomy, Building 233/234, University of Aarhus, DK-8000 Aarhus, Denmark. Phone: +45-894-23008; Fax: +45-861-98664; E-mail: rofe{at}ana.au.dk

Since the turn of the 21st century, gene knockout mice have been created for all major urea transporters that are expressed in the kidney: the collecting duct urea transporters UT-A1 and UT-A3, the descending thin limb isoform UT-A2, and the descending vasa recta isoform UT-B. This article discusses the new insights that the results from studies in these mice have produced in the understanding of the role of urea in the urinary concentrating mechanism and kidney function. Following is a summary of the major findings: (1) Urea accumulation in the inner medullary interstitium depends on rapid transport of urea from the inner medullary collecting duct (IMCD) lumen via UT-A1 and/or UT-A3; (2) as proposed by Robert Berliner and colleagues in the 1950s, the role of IMCD urea transporters in water conservation is to prevent a urea-induced osmotic diuresis; (3) the absence of IMCD urea transport does not prevent the concentration of NaCl in the inner medulla, contrary to what would be predicted from the passive countercurrent multiplier mechanism in the form proposed by Kokko and Rector and Stephenson; (4) deletion of UT-B (vasa recta isoform) has a much greater effect on urinary concentration than deletion of UT-A2 (descending limb isoform), suggesting that the recycling of urea between the vasa recta and the renal tubules quantitatively is less important than classic countercurrent exchange; and (5) urea reabsorption from the IMCD and the process of urea recycling are not important elements of the mechanism of protein-induced increases in GFR. In addition, the clinical relevance of these studies is discussed, and it is suggested that inhibitors that specifically target collecting duct urea transporters have the potential for clinical use as potassium-sparing diuretics that function by creation of urea-dependent osmotic diuresis.

Related Articles

Ethnic Differences in Urine Concentration: Possible Relationship to Blood Pressure

Lise Bankir, Julie Perucca, and Myron H. Weinberger
Clin. J. Am. Soc. Nephrol. 2007 2: 304-312. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				M.-J. Yu, T. Pisitkun, G. Wang, J. F. Aranda, P. A. Gonzales, D. Tchapyjnikov, R.-F. Shen, M. A. Alonso, and M. A. Knepper Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct Am J Physiol Cell Physiol, September 1, 2008; 295(3): C661 - C678. [Abstract] [Full Text] [PDF]

				J. J. Bolivar, D. Tapia, G. Arenas, M. Castanon-Arreola, H. Torres, and E. Galarraga A hyperpolarization-activated, cyclic nucleotide-gated, (Ih-like) cationic current and HCN gene expression in renal inner medullary collecting duct cells Am J Physiol Cell Physiol, April 1, 2008; 294(4): C893 - C906. [Abstract] [Full Text] [PDF]

				P. Uawithya, T. Pisitkun, B. E. Ruttenberg, and M. A. Knepper Transcriptional profiling of native inner medullary collecting duct cells from rat kidney Physiol Genomics, January 17, 2008; 32(2): 229 - 253. [Abstract] [Full Text] [PDF]

				T. L. Pallone Aquaporin 1, Urea Transporters, and Renal Vascular Bundles J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2798 - 2800. [Full Text] [PDF]

				J. M. Sands Critical Role of Urea in the Urine-Concentrating Mechanism J. Am. Soc. Nephrol., March 1, 2007; 18(3): 670 - 671. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673