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An analysis of renal tubular acidosis by the Stewart method

Pediatric Nephrology volume 21, pages 206–211 (2006)Cite this article

Abstract

Renal tubular acidosis (RTA) comprises a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. To investigate the role of chloride, we performed hypotonic (0.45%) saline-loading experiments in 12 children with alkali-treated distal RTA (dRTA) and compared the results with data obtained from 17 healthy control subjects. In patients, but not in controls, saline loading induced both hyperchloremia and metabolic acidosis. Hyperchloremia was associated with high total and high distal fractional reabsorption of chloride [CH20/(CH20+CCl)]. The increase in plasma chloride varied inversely with the fractional excretion of chloride (CCl) and correlated with the decrease in blood pH. However, the urinary excretion of bicarbonate did not correlate with either changes in blood pH or plasma bicarbonate concentration. Our findings suggest that the mechanism of hyperchloremia was enhanced Cl−/HCO3− exchange by the distal tubule. The resulting metabolic acidosis is better explained by changes in the strong ion difference (the Stewart theory) than by changes in the urine bicarbonate excretion (the traditional theory).

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References

  1. Rodriguez-Soriano J (2000) New insights into the pathogenesis of renal tubular acidosis from functional to molecular studies. Pediatric Nephrol 14:1121–1136

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Stewart PA (1981) How to understand acid base balance. In: A quantitative acid–base primer for biology and medicine. Elsevier, New York

  4. Stewart PA (1983) Modern quantitative acid–base chemistry. Can J Physiol Pharmacol 61:1444–1461

    PubMed  Google Scholar 

  5. Corey HE (2003) Stewart and beyond: new models of acid–base balance. Kidney Int 64:777–787

    Article  PubMed  Google Scholar 

  6. Karet FE, Gainza FJ, Gyory AZ, Unwin RJ, Wrong O, Tanner MJ, Nayir A, Alpay H, Santos F, Hulton SA, Bakkaloglu A, Ozen S, Cunningham MJ, di Pietro A, Walker WG, Lifton RP (1998) Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis. Proc Natl Acad Sci USA 95:6337–6342

    Article  PubMed  Google Scholar 

  7. Karet FE, Finberg KE, Nelson RD, Nayir A, Mocan H, Sanjad SA, Rodriguez-Soriano J, Santos F, Cremers CW, Di Pietro A, Hoffbrand BI, Winiarski J, Bakkaloglu A, Ozen S, Dusunsel R, Goodyer P, Hulton SA, Wu DK, Skvorak AB, Morton CC, Cunningham MJ, Jha V, Lifton RP (1999) Mutations in the gene encoding the B1 subunit of H+-ATPase. Nat Genet 21:84–90

    Article  PubMed  Google Scholar 

  8. Eady N, Fritz DM, Rungroj N, Giersch AB, Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A, Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S, Mocan H, Nayir A, Ozen S, Rodriguez-Soriano J, Sanjad SA, Tasic V, Taylor CM, Topaloglu R, Smith AN, Karet FE (2002) Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss . J Med Genet 39:796–803

    Article  PubMed  Google Scholar 

  9. Rodriguez-Soriano J, Vallo A, Castillo G, Oliveros R (1980) Renal handling of water and sodium in children with proximal and distal renal tubular acidosis. Nephron 25:193–198

    PubMed  Google Scholar 

  10. Rodriguez-Soriano J, Vallo A, Castillo G, Oliveros R (1981) Renal handling of water and sodium in infancy and childhood: a study using clearance methods during hypotonic saline diuresis. Kidney Int 20:700–704

    PubMed  Google Scholar 

  11. Rodriguez-Soriano J, Vallo A, Sanjurjo P, Castillo G, OIiveros R (1986) Hyporeninemic hypoaldosteronism in children with chronic renal failure. J Pediatr 109:476–482

    PubMed  Google Scholar 

  12. Jentsch TJ (2005) Chloride transport in the kidney: lessons from human disease and knockout mice. J Am Soc Nephrol 16:1549–1561

    Article  PubMed  Google Scholar 

  13. Karet FE (2002) Inherited distal renal tubular acidosis. J Am Soc Nephrol 13:2178–2184

    Article  PubMed  Google Scholar 

  14. Rungroj N, Devonald MA, Cuthbert AW, Reimann F, Akkarapatumwong V, Yenchitsomanus PT, Bennett WM, Karet FE (2004) A novel missense mutation in AE1 causing autosomal dominant distal renal tubular acidosis remains normal transport function but is mistargeted in polarized epithelial cells. J Biol Chem 279:13833–13838

    Article  PubMed  Google Scholar 

  15. Schwartz GJ, Tsuruoka S, Soundarapandian V, Petrovic Mian A, Al-Awqati Q (2002) Acid incubation reverses the polarity of intercalated cell transporters, an effect medicated by hensin. J Clin Invest 109:89–99

    Article  PubMed  Google Scholar 

  16. Singer RB, Hastings AG (1948) Improved clinical method for estimation of disturbance of acid–base balance of human blood. Medicine (Baltimore) 27:223–242

    Google Scholar 

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Affiliations

  1. The Children’s Kidney Center of New Jersey, Goryeb Children’s Hospital, Morristown Memorial Hospital, 100 Madison Avenue, Morristown, New Jersey, 07962, USA

    Howard E. Corey

  2. Department of Pediatrics, Division of Pediatric Nephrology, Hospital de Cruces and Basque University School of Medicine, Bilbao, Spain

    Alfredo Vallo & Juan Rodríguez-Soriano

Authors
  1. Howard E. Corey
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  2. Alfredo Vallo
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  3. Juan Rodríguez-Soriano
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Correspondence to Howard E. Corey.

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Corey, H.E., Vallo, A. & Rodríguez-Soriano, J. An analysis of renal tubular acidosis by the Stewart method. Pediatr Nephrol 21, 206–211 (2006). https://doi.org/10.1007/s00467-005-2081-8

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  • DOI: https://doi.org/10.1007/s00467-005-2081-8

Keywords

  • Strong ion difference
  • Renal tubular acidosis
  • Stewart theory
  • Acid–base balance
  • Hyperchloremia
  • Cl−/HCO3− exchange