Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels

Yimin Shi; Chunling Li; Thomsen, Klaus; Jørgensen, Troels Munch; Knepper, Mark A.; Nielsen, Søren; Djurhuus, Jens Christian; Frøki&aezig;r, Jørgen
July 2004
Kidney International;Jul2004, Vol. 66 Issue 1, p203
Academic Journal
Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels. Background. Congenital urinary tract obstruction is a common cause of renal insufficiency in the neonate and during infancy. Recently, we demonstrated that ureteral obstruction in adult rats is associated with reduction in the abundance of renal aquaporins (AQPs) and renal sodium transporters, which paralleled an impaired urinary concentrating capacity. Methods. In the present study, renal handling of sodium and water, together with the expression of renal aquaporins and major renal sodium transporters, was examined in rats with neonatally induced partial unilateral ureteral obstruction (PUUO) within the first 48 hours of life to clarify the molecular mechanisms involved in the tubular functional defects in response to congenital obstruction. Rats were then followed for 12 or 24 weeks. Results. Neonatal PUUO caused a progressive reduction in single kidney glomerular filtration rate (SKGFR) on the obstructed side to 43% of controls at 12 weeks (115 ± 28 vs. 267 ± 36 μL/min/100g bw, P < 0.05), and 31% of controls at 24 weeks (106 ± 24 vs. 343 ± 41 μL/min/100g bw, P < 0.05). Na-K-ATPase abundance was decreased in the obstructed kidney compared with the nonobstructed kidney at 24 weeks (79 ± 6%, P < 0.05), and the abundance of bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) located to the medullary thick ascending limb (mTAL) of the obstructed kidney was significantly reduced both at 12 weeks (42 ± 10%, P < 0.05) and 24 weeks (50 ± 10%, P < 0.05). Immunohistochemistry confirmed down-regulation of BSC-1 both at 12 and 24 weeks after onset of obstruction. Consistent with this, sodium excretion from the obstructed kidney was increased at 12 weeks (0.13 ± 0.03 vs. 0.04 ± 0.01 μmol/min/100g bw, P < 0.05), and persisted 24 weeks after onset of PUUO (0.15 ± 0.02 vs. 0.06 ± 0.01 μmol/min/100g bw, P < 0.05). AQP2 abundance in the collecting duct was also reduced both at 12 weeks (68 ± 5%, P < 0.05) and at 24 weeks (69 ± 13%, P < 0.05). Consistent with this, solute-free water reabsorption was decreased in the obstructed kidney at 12 weeks (0.61 ± 0.42 vs. 1.97 ± 0.63 μL/min/100g bw, P < 0.05) and remained decreased after 24 weeks of PUUO (0.42 ± 0.04 vs. 1.56 ± 0.39 μL/min/100g bw, P < 0.05). Conclusion. Major sodium transporters and aquaporins in the obstructed kidney are down-regulated in response to neonatally induced PUUO, which indicates that these transporters may play a crucial role for the persistent reduction in renal handling of sodium and water in response to PUUO.


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