Molecular basis for the dialysis disequilibrium syndrome: altered aquaporin and urea transporter expression in the brain

Abstract

Cerebral disorders caused by brain oedema characterize the dialysis disequilibrium syndrome, a complication of rapid haemodialysis. Brain oedema is presumably caused by the 'reverse urea effect', i.e. the significant urea gradient between blood and brain after dialysis, with, as a result, an inflow of water into the brain. To assess the molecular basis of this effect, we examined the expression of urea transporter UT-B1 and aquaporin (AQP) 4 and AQP9 in the brain of uraemic rats. Brain, kidneys and one testis were collected from four sham-operated (control) and four uraemic rats, 10 weeks after 5/6 nephrectomy (Nx). Protein abundance was measured by semi-quantitave immunoblotting using affinity-purified rabbit anti-rat antibodies applied on tissue crude homogenates. The results are expressed as means+/-SE of band density (arbitrary units). In Nx compared with control rats, the brain expression of UT-B1 was reduced by half (32+/-3 vs 62+/-8, P<0.01) whereas that of AQ4 was doubled (251+/-13 vs 135+/-5, P<0.001), and that of AQP9 increased by 65% (253+/-22 vs 154+/-10, P<0.01). UT-B1 expression was also lowered by Nx in kidney medulla (45+/-21 vs 141+/-4, P<0.01) but was unchanged in testis. The conjunction of a reduced expression of UT-B and an increased expression of AQPs in brain cells may bring a new clue to understanding the DDS mechanism. Because of low UT-B abundance, urea exit from astrocytes is most probably delayed during rapid removal of extracellular urea through fast dialysis. This creates an osmotic driving force that promotes water entry into the cells (favoured by abundant AQPs) and subsequent brain swelling.