Lack of UT-B in vasa recta and red blood cells prevents urea-induced improvement of urinary concentrating ability.
Recycling of urea within the renal medulla is known to play an important role in the capacity of the kidney to concentrate urine. This recycling occurs simultaneously through a tubular and a vascular route (i.e., through the loops of Henle and vasa recta, respectively). In the present study, transgenic mice with a selective deficiency in UT-B (the urea transporter protein expressed in descending vasa recta and red blood cells), were used to evaluate the specific contribution of vascular urea recycling to overall urine-concentrating ability (UCA). The renal handling of urea was studied in normal conditions and after acute or chronic alterations in urea excretion (acute urea loading or variations in protein intake, respectively). In normal conditions, UT-B null mice exhibited a 44% elevation in plasma urea (Purea), a normal creatinine clearance, but a 25% decrease in urea clearance, with no change in that of sodium and potassium. Acute urea loading induced a progressive increase in urinary urea concentration (Uurea) in wild-type mice and a subsequent improvement in their UCA in contrast to UT-B null mice, in which urinary osmolality and Uurea did not rise, due to the failure to accumulate urea in the medulla. With increasing protein intake (from 10 to 40% protein in diet, leading to a 5-fold increase in urea excretion), Purea was further increased in null mice while little change was observed in wild-type mice, and null mice were not able to increase Uurea as did wild-type mice. In conclusion, this study in UT-B-deficient mice reveals that countercurrent exchange of urea in renal medullary vessels and red blood cells accounts for a major part of the kidney's concentrating ability and for the adaptation of renal urea handling during a high-protein intake.
Bankir
Lise
L
Cardiovascular Research Institute, University of California, 1246 Health Sciences East Tower, San Francisco, CA 94143-0521, USA.
Chen
Kai
K
Yang
Baoxue
B
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D004044:Dietary Proteins / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007671:Kidney Concentrating Ability / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014508:Urea / Q000493:pharmacokinetics*
D004044:Dietary Proteins; D026901:Membrane Transport Proteins; C452857:urea transporter B, mouse; D014508:Urea; D003404:Creatinine