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

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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.

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Acknowledgments

The authors thank Gitte Kall, Line V. Nielsen, Inger Merete Paulsen, Gitte Skou and Hongyan Li for expert technical assistance. The Water and Salt Research Centre at the University of Aarhus is established and supported by the Danish National Research Foundation (Danmarks Grundforskningsfond). Support for this study was provided by The Karen Elise Jensen Foundation, The Commission of the European Union (QRLT-2000-00987 and QLRT-2000-00778), The Human Frontier Science Program, The WIRED program (Nordic Council and the Nordic Centre of Excellence Program in Molecular Medicine), The Novo Nordisk Foundation, The Danish Medical Research Council, The University of Aarhus, and The Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Korea (A080143, THK).

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Authors and Affiliations

  1. The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark

    Guixian Wang, Sukru Oguzkan Topcu, Søren Nielsen & Jørgen Frøkiær

  2. Institute of Clinical Medicine, University of Aarhus, Aarhus C, Denmark

    Guixian Wang, Sukru Oguzkan Topcu, Jens Christian Djurhuus & Jørgen Frøkiær

  3. Department of Paediatric Surgery, 1st and 3rd Teaching Hospital and Institute of Clinical Medicine for Henan Universities, Zhengzhou University, Zhengzhou, China

    Guixian Wang & Jianguo Wen

  4. Department of Nephrology, Aarhus University Hospital-Aalborg, Aalborg, Denmark

    Troels Ring

  5. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, 700-422, Korea

    Tae-Hwan Kwon

  6. Institute of Anatomy, University of Aarhus, Aarhus C, Denmark

    Søren Nielsen

  7. Department of Clinical Physiology, Aarhus University Hospital-Skejby, Aarhus N, Denmark

    Jørgen Frøkiær

  8. The Water and Salt Research Center/Institute of Clinical Medicine, Aarhus University Hospital-Skejby, Aarhus, 8200, Denmark

    Jørgen Frøkiær

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  1. Guixian Wang
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Wang, G., Topcu, S.O., Ring, T. et al. Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction. Pediatr Nephrol 24, 1487–1500 (2009). https://doi.org/10.1007/s00467-009-1193-y

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