Abstract: Objectives To investigate the expression changes of aquaporin (AQP) 1, 5 and urea transporter B1 (UT-B1) in brain tissues of mice with chronic renal failure, which may be useful to explain the molecular basis of brain- type dialysis disequilibrium syndrome in humans. Methods We randomly divided BALB/c mice into 3 groups: normal group, sham operation group, and chronic renal failure group after diathermy of the 2/3 right kidney cortex and then nephrectomy of the left kidney. Five mice in each group were sacrificed at 10 days, 40 days and 70 days after operation. Renal pathology, serum creatinine and blood urea nitrogen were examined. AQP and UT-B1 expressions in brain were assayed by western blotting. Results In chronic renal failure group at 40, 70 days after operation, renal pathological examination showed glomerular proliferation and sclerosis, kidney tubule atrophy and fibrosis. In chronic renal failure group at 10, 40, 70 days after operation, serum creatinine was 841.80±336.93 μmol/L, 1885.17±689.49 μmol/L, and 1276.56±496.09 μmol/L, respectively, significantly higher than that in normal group and that in sham group at 10 days (F= 26.768, P=0.007), 40 days (F=34.928, P=0.004) and 70 days (F=29.998, P=0.005) after operation. In chronic renal failure group, brain AQP1 expression increased by 46.67% (1.10±0.05 vs. 0.75±0.05, t =0.122, P=0.001) at 10 days after operation, by 28.98% (0.89±0.02 vs. 0.69±0.04, t=4.926, P=0.001) at 40 days after operation, and by 30.26% (0.99±0.07 vs. 0.76±0.05, t= 8.471, P=0.001) at 70 days after operation, as compared with that in control group; brain AQP5 expression increased by 41.09% (1.03±0.03 vs. 0.73±0.02, t=0.012, P=0.001) at 10 days after operation, by 20.83% (0.87±0.03 vs. 0.72±0.04, t= 0.857, P=0.003) at 40 days after operation, and by 45.67% (1.18±0.09 vs. 0.81±0.04, t =3.352, P=0.001) at 70 days after operation, as compared with that in control group; brain UT-B1 expression reduced significantly as compared with that in normal group and in sham operation group at 10 days, 40 days and 70 days after operation. Conclusions The increase of AQP1, 5 expressions and decrease of UT-B1 expression in brain of chronic renal failure mice may suggest the molecular basis of brain-type dialysis disequilibrium syndrome in humans. During rapid hemodialysis, delayed urea clearance happened due to the low expression of UT-B1, resulting in a concentration gradient of urea between brain and blood which drives water into brain by the over-expressed aquaporins and brain edema.

Key words: Brain-Type dialysis disequilibrium syndrome, Urea transport- protein, Chronic Renal Failure, Aquaporin, BrainEdema