Massive reduction of urea transporters in remnant kidney and brain of uremic rats

Mc. Hu et al., Massive reduction of urea transporters in remnant kidney and brain of uremic rats, KIDNEY INT, 58(3), 2000, pp. 1202-1210
Citations number
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
ISSN journal
0085-2538 → ACNP
Year of publication
1202 - 1210
SICI code
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.