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01-08-2009 | Original Article

Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction

Authors: Guixian Wang, Sukru Oguzkan Topcu, Troels Ring, Jianguo Wen, Jens Christian Djurhuus, Tae-Hwan Kwon, Søren Nielsen, Jørgen Frøkiær

Published in: Pediatric Nephrology | Issue 8/2009

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.

Bascands JL, Schanstra JP (2005) Obstructive nephropathy: insights from genetically engineered animals. Kidney Int 68:925–937PubMedPubMedCentral

Koff SA, Campbell KD (1994) The nonoperative management of unilateral neonatal hydronephrosis: natural history of poorly functioning kidneys. J Urol 152:593–595PubMed

Peters CA (1997) Obstruction of the fetal urinary tract. J Am Soc Nephrol 8:653–663PubMed

Elder JS (1997) Antenatal hydronephrosis. Fetal and neonatal management. Pediatr Clin North Am 44:1299–1321

Klahr S (2001) Urinary tract obstruction: In: Schrier RW (ed) Disease of the kidney and urinary tract, vol 1, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 757-787

Li C, Wang W, Kwon TH, Knepper MA, Nielsen S, Frøkiaer J (2003) Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction. Am J Physiol Renal Physiol 284:F155–F166PubMed

Li C, Wang W, Knepper MA, Nielsen S, Frøkiaer J (2003) Downregulation of renal aquaporins in response to unilateral ureteral obstruction. Am J Physiol Renal Physiol 284:F1066–F1079PubMed

Frokiaer J, Christensen BM, Marples D, Djurhuus JC, Jensen UB, Knepper MA, Nielsen S (1997) Downregulation of aquaporin-2 parallels changes in renal water excretion in unilateral ureteral obstruction. Am J Physiol 273:F213–F223PubMed

Thirakomen K, Kozlov N, Arruda JA, Kurtzman NA (1976) Renal hydrogen ion secretion after release of unilateral ureteral obstruction. Am J Physiol 231:1233–1239PubMed

10.

Walls J, Buerkert JE, Purkerson ML, Klahr S (1975) Nature of the acidifying defect after the relief of ureteral obstruction. Kidney Int 7:304–316PubMed

11.

Wang G, Kim SW, Djurhuus JC, Nielsen S, Frokiaer J (2007) Downregulation of renal acid-base transporters is associated with a urinary acidification defect in rats with unilateral ureter obstruction (abstract). J Am Soc Nephrol 18:592A

12.

Josephson S, Jacobsson E, Larsson E (1997) Experimental partial ureteric obstruction in newborn rats. IX. Renal morphology and function after 1 year of obstruction. Urol Int 59:16–22PubMed

13.

Shi Y, Li C, Thomsen K, Jørgensen TM, Knepper MA, Nielsen S, Djurhuus JC, Frøkiaer J (2004) Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels. Kidney Int 66:203–215PubMed

14.

Rodriguez SJ (2002) Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13:2160–2170

15.

Unwin RJ, Shirley DG, Capasso G (2002) Urinary acidification and distal renal tubular acidosis. J Nephrol 15[Suppl 5]:S142–S150PubMed

16.

Lee Hamm L (2004) Renal acidification mechanism. In: Brenner BM (ed) Brenner and Rector's—the kidney, vol 1, 7th edn. Saunders, Philadelphia, pp 497–534

17.

Igarashi T, Sekine T, Watanabe H (2002) Molecular basis of proximal renal tubular acidosis. J Nephrol 15[Suppl 5]:S135–S141PubMed

18.

Schultheis PJ, Clarke LL, Meneton P, Miller ML, Soleimani M, Gawenis LR, Riddle TM, Duffy JJ, Doetschman T, Wang T, Giebisch G, Aronson PS, Lorenz JN, Shull GE (1998) Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H + exchanger. Nat Genet 19:282–285PubMed

19.

Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y, Kunimi M, Tsukamoto K, Satoh H, Shimadzu M, Tozawa F, Mori T, Shiobara M, Seki G, Endou H (1999) Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet 23:264–266PubMed

20.

Choi I, Aalkjaer C, Boulpaep EL, Boron WF (2000) An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel. Nature 405:571–575PubMed

21.

Kwon TH, Fulton C, Wang W, Kurtz I, Frøkiaer J, Aalkjaer C, Nielsen S (2002) Chronic metabolic acidosis upregulates rat kidney Na-HCO cotransporters NBCn1 and NBC3 but not NBC1. Am J Physiol Renal Physiol 282:F341–F351PubMed

22.

Vorum H, Kwon TH, Fulton C, Simonsen B, Choi I, Boron W, Maunsbach AB, Nielsen S, Aalkjaer C (2000) Immunolocalization of electroneutral Na-HCO(3)(-) cotransporter in rat kidney. Am J Physiol Renal Physiol 279:F901–F909PubMed

23.

Odgaard E, Jakobsen JK, Frische S, Praetorius J, Nielsen S, Aalkjaer C, Leipziger J (2004) Basolateral Na⁺-dependent HCO_3- transporter NBCn1-mediated HCO_3- influx in rat medullary thick ascending limb. J Physiol 555:205–218PubMed

24.

Alper SL, Natale J, Gluck S, Lodish HF, Brown D (1989) Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H + -ATPase. Proc Natl Acad Sci U S A 86:5429–5433PubMedPubMedCentral

25.

Wall SM (2005) Recent advances in our understanding of intercalated cells. Curr Opin Nephrol Hypertens 14:480–484PubMed

26.

Kashgarian M, Biemesderfer D, Caplan M, Forbush BI II (1985) Monoclonal antibody to Na, K-ATPase: immunocytochemical localization along nephron segments. Kidney Int 28:899–913PubMed

27.

Koeppen BM, Steinmetz PR (1983) Basic mechanisms of urinary acidification. Med Clin North Am 67:753–770PubMed

28.

Wall SM (2000) Impact of K(+) homeostasis on net acid secretion in rat terminal inner medullary collecting duct: role of the Na, K-ATPase. Am J Kidney Dis 36:1079–1088PubMed

29.

Wen JG, Chen Y, Frokiaer J, Jørgensen TM, Djurhuus JC (1998) Experimental partial unilateral ureter obstruction. I. Pressure flow relationship in a rat model with mild and severe acute ureter obstruction. J Urol 160:1567–1571

30.

Ulm AH, Miller F (1962) An operation to produce experimental reversible hydronephrosis in dogs. J Urol 88:337–341PubMed

31.

Phifer CB, Terry LM (1986) Use of hypothermia for general anesthesia in preweanling rodents. Physiol Behav 38:887–890PubMed

32.

Frische S, Kwon TH, Frokiaer J, Madsen KM, Nielsen S (2003) Regulated expression of pendrin in rat kidney in response to chronic NH4Cl or NaHCO3 loading. Am J Physiol Renal Physiol 284:F584–F593PubMed

33.

Good DW (1988) Active absorption of NH4 + by rat medullary thick ascending limb: inhibition by potassium. Am J Physiol 255:F78–F87PubMed

34.

Wang G, Li C, Kim SW, Ring T, Wen J, Djurhuus JC, Wang W, Nielsen S, Frøkiaer J (2008) Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney. Am J Physiol Renal Physiol 295:F497–F506PubMed

35.

Alon U, Kodroff MB, Broecker BH, Kirkpatrick BV, Chan JC (1984) Renal tubular acidosis type 4 in neonatal unilateral kidney diseases. J Pediatr 104:855–860PubMed

36.

Marra G, Goj V, Appiani AC, Dell Agnola CA, Tirelli SA, Tadini B, Nicolini U, Cavanna G, Assael BM (1987) Persistent tubular resistance to aldosterone in infants with congenital hydronephrosis corrected neonatally. J Pediatr 110:868–872PubMed

37.

Wen JG, Ringgaard S, Jorgensen TM, Stødkilde-Jørgensen H, Djurhuus JC, Frøkiaer J (2002) Long-term effects of partial unilateral ureteral obstruction on renal hemodynamics and morphology in newborn rats: a magnetic resonance imaging study. Urol Res 30:205–212PubMed

38.

Eskild-Jensen A, Paulsen LF, Wogensen L, Olesen P, Pedersen L, Frøkiaer J, Nyengaard JR (2007) AT1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction. Am J Physiol Renal Physiol 292:F1771–F1781PubMed

39.

Lange-Sperandio B, Trautmann A, Eickelberg O, Jayachandran A, Oberle S, Schmidutz F, Rodenbeck B, Hömme M, Horuk R, Schaefer F (2007) Leukocytes induce epithelial to mesenchymal transition after unilateral ureteral obstruction in neonatal mice. Am J Pathol 171:861–871PubMedPubMedCentral

40.

Ma FY, Tesch GH, Flavell RA, Davis RJ, Nikolic-Paterson DJ (2007) MKK3–p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney. Am J Physiol Renal Physiol 293:F1556–F1563PubMed

41.

Park SH, Choi MJ, Song IK, Choi SY, Nam JO, Kim CD, Lee BH, Park RW, Park KM, Kim YJ, Kim IS, Kwon TH, Kim YL (2007) Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition. J Am Soc Nephrol 18:1497–1507PubMed

42.

Hamm LL (2004) Renal acidification mechanisms. In: Brenner (ed) Brenner & Rector's—the kidney, vol 1, 7th edn. Saunders, Philadelphia, pp 497-534

43.

Maunsbach AB, Vorum H, Kwon TH, Nielsen S, Simonsen B, Choi I, Schmitt BM, Boron WF, Aalkjaer C (2000) Immunoelectron microscopic localization of the electrogenic Na/HCO(3) cotransporter in rat and ambystoma kidney. J Am Soc Nephrol 11:2179–2189PubMed

44.

Dinour D, Chang MH, Satoh J, Smith BL, Angle N, Knecht A, Serban I, Holtzman EJ, Romero MF (2004) A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem 279:52238–52246PubMed

45.

Horita S, Yamada H, Inatomi J, Moriyama N, Sekine T, Igarashi T, Endo Y, Dasouki M, Ekim M, Al-Gazali L, Shimadzu M, Seki G, Fujita T (2005) Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol 16:2270–2278PubMed

46.

Gawenis LR, Bradford EM, Prasad V, Lorenz JN, Simpson JE, Clarke LL, Woo AL, Grisham C, Sanford LP, Doetschman T, Miller ML, Shull GE (2007) Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. J Biol Chem 282:9042–9052PubMed

47.

Han JS, Kim GH, Kim J, Jeon US, Joo KW, Na KY, Ahn C, Kim S, Lee SE, Lee JS (2002) Secretory-defect distal renal tubular acidosis is associated with transporter defect in H(+)-ATPase and anion exchanger-1. J Am Soc Nephrol 13:1425–1432PubMed

48.

Valles P, Merlo V, Beron W, Manucha W (1999) Recovery of distal nephron enzyme activity after release of unilateral ureteral obstruction. J Urol 161:641–648PubMed

49.

Bastani B, Purcell H, Hemken P, Trigg D, Gluck S (1991) Expression and distribution of renal vacuolar proton-translocating adenosine triphosphatase in response to chronic acid and alkali loads in the rat. J Clin Invest 88:126–136PubMedPubMedCentral

50.

Kim YH, Kwon TH, Frische S, Kim J, Tisher CC, Madsen KM, Nielsen S (2002) Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidney. Am J Physiol Renal Physiol 283:F744–F754PubMed

51.

Rizzo M, Capasso G, Bleich M, Pica A, Grimaldi D, Bindels RJ, Greger R (2000) Effect of chronic metabolic acidosis on calbindin expression along the rat distal tubule. J Am Soc Nephrol 11:203–210PubMed

52.

Wesson DE, Simoni J (2009) Increased tissue acid mediates a progressive decline in the glomerular filtration rate of animals with reduced nephron mass. Kidney Int 75:929–935PubMed

53.

Phisitkul S, Hacker C, Simoni J, Tran RM, Wesson DE (2008) Dietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptors. Kidney Int 73:192–199PubMed

54.

Shi Y, Pedersen M, Li C, Wen JG, Thomsen K, Stødkilde-Jørgensen H, Jørgensen TM, Knepper MA, Nielsen S, Djurhuus JC, Frøkiaer J (2004) Early release of neonatal ureteral obstruction preserves renal function. Am J Physiol Renal Physiol 286:F1087–F1099PubMed

55.

Thornhill BA, Burt LE, Chen C, Forbes MS, Chevalier RL (2005) Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction. Kidney Int 67:42–52PubMed

56.

Bhangdia DK, Gulmi FA, Chou SY, Mooppan UM, Kim H (2003) Alterations of renal hemodynamics in unilateral ureteral obstruction mediated by activation of endothelin receptor subtypes. J Urol 170:2057–2062PubMed

Title: Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction
Authors: Guixian Wang
Sukru Oguzkan Topcu
Troels Ring
Jianguo Wen
Jens Christian Djurhuus
Tae-Hwan Kwon
Søren Nielsen
Jørgen Frøkiær
Publication date: 01-08-2009
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 8/2009
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-009-1193-y

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Springer Medicine

Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction

Abstract

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Abstract

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