title: Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction.
abstract: Congenital obstructive nephropathy accounts for a major proportion of renal insufficiency in infancy and childhood. In an earlier investigation we demonstrated that bilateral complete ureteral obstruction (BUO) in rats is associated with inadequate urinary acidification [Am J Physiol Renal Physiol. 295(2):F497-506, 2008]. The aim of the study reported here was to determine whether this defect is also associated with unilateral ureteral obstruction (UUO), which is clinically more common than BUO. The time-course of the changes in protein expression levels of major renal acid-base transporters was examined at 7 and 14 weeks in rats with neonatally induced partial unilateral ureteral obstruction (PUUO), which was performed within the first 48 h of life. We observed that protein expression of the renal acid-base transporters NHE3, NBC1, NBCn1, pendrin and Na(+)-K(+)-ATPase was increased in both obstructed and non-obstructed kidneys 7 weeks after the induction of neonatal PUUO. This was confirmed by immunocytochemistry. In contrast, 14 weeks after the induction of PUUO, there was a significant downregulation of the renal acid-base transporters NBC1, NBCn1 and Na(+)-K(+)-ATPase in the obstructed kidneys. These time/age-dependent changes in protein expression were associated with parallel changes in renal function resulting in urine acidification in response to exogenous acid loading. In conclusion, these results show that downregulation of protein expression is a time/age-dependent response to PUUO, which could contribute to the decreased net acid excretion and development of metabolic acidosis in neonatal rats with PUUO.
authors.affiliation: The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark.
authors.forename: Guixian
authors.initials: G
authors.lastname: Wang
authors.forename: Sukru Oguzkan
authors.initials: SO
authors.lastname: Topcu
authors.forename: Troels
authors.initials: T
authors.lastname: Ring
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wen
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Djurhuus
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016623:Ion Pumps / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D014517:Ureteral Obstruction / Q000378:metabolism*
chemical_list: D016623:Ion Pumps; C422004:Slc4a4 protein, rat; C498902:Slc4a7 protein, rat; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase