Background. The facilitated urea transporters (UT), UT-A1, UT-A2, and UT-B1
, are involved in intrarenal recycling of urea, an essential feature of the
urinary concentrating mechanism, which is impaired in chronic renal failur
e (CRF). In this study, the expression of these UTs was examined in experim
entally induced CRF.
Methods. The abundance of mRNA was measured by Northern analysis and that o
f corresponding proteins by Western blotting in rats one and five weeks aft
er 5/6 nephrectomy (Nx).
Results. At five weeks, urine output was enhanced threefold with a concomit
ant decrease in urine osmolality. The marked rise in plasma urea concentrat
ion and fall in urinary urea concentration resulted in a 30-fold decrease i
n the urine/plasma (UTP) urea concentration ratio, while the U/P osmoles ra
tio fell only fourfold. A dramatic decrease in mRNA abundance for the three
UTs was observed, bringing their level at five weeks to 1/10th or less of
control values. Immunoblotting showed complete disappearance of the 97 and
117 kD bands of UT-A1, and considerable reduction of UT-A2 and UT-B1 in the
renal medulla. Similar, but less intense, changes were observed at one-wee
k post-Nx. In addition to the kidney, UT-BI is also normally expressed in b
rain and testis. In the brain, its mRNA expression remained normal one-week
post-Nx, but decreased to about 30% of normal at five-weeks post-Nx, where
as no change was seen in testis.
Conclusions. (I) The decline in urinary concentrating ability seen in CRF i
s largely due to a major reduction of UTs involved in the process of urea c
oncentration in the urine, while factors enabling the concentration of othe
r solutes are less intensely affected. (2) The marked reduction of brain UT
expression in CRF may be responsible for brain edema of dialysis disequili
brium syndrome observed in some patients after fast dialysis.