Skip to main content

Advertisement

SpringerLink
Log in

Renal Tubular Acidosis

  • Review Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Soriano JR. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol. 2002;13:2160–70.

    Google Scholar 

  2. Guo YM, Liu Y, Liu M, et al. Na+/HCO3− cotransporter NBCn2 mediates HCO3−reclamation in the apical membrane of renal proximal tubules. J Am Soc Nephrol. 2017;28:2409–19.

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Curthoys NP, Moe OW. Proximal tubule function and response to acidosis. Clin J Am Soc Nephrol. 2014;9:1627–38.

    PubMed  CAS  Google Scholar 

  4. Wagner C, Devuyst O, Bourgeois S, Mohebbi N. Regulated acid–base transport in the collecting duct. Eur J Phys. 2009;458:137–56.

    CAS  Google Scholar 

  5. Chambrey R, Trepiccione F. Relative roles of principal and intercalated cells in the regulation of sodium balance and blood pressure. Curr Hypertens Rep. 2015;17:538.

    PubMed  Google Scholar 

  6. Weiner ID, Verlander JW. Ammonia transporters and their role in acid-base balance. Physiol Rev. 2017;97:465–94.

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Mioni R, Mioni G. Titratable acidity: a Pitts concept revisited. Scand J Clin Lab Invest. 2014;74:408–13.

    PubMed  Google Scholar 

  8. Trepiccione F, Prosperi F, de la Motte LR, et al. New findings on the pathogenesis of distal renal tubular acidosis. Kidney Dis (Basel). 2017;3:98–105.

    Google Scholar 

  9. Foreman JW. Fanconi syndrome. Pediatr Clin N Am. 2019;66:159–67.

    Google Scholar 

  10. Cherqui S, Courtoy PJ. The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives. Nat Rev Nephrol. 2017;13:115–31.

    PubMed  CAS  Google Scholar 

  11. Ehlayel AM, Copelovitch L. Update on dent disease. Pediatr Clin N Am. 2019;66:169–78.

    Google Scholar 

  12. Rungroj N, Nettuwakul C, Sawasdee N, et al. Distal renal tubular acidosis caused by tryptophan-aspartate repeat domain 72 (WDR72) mutations. Clin Genet. 2018;94:409–18.

    PubMed  CAS  Google Scholar 

  13. Jobst-Schwan T, Klämbt V, Tarsio M, et al. Whole exome sequencing identified ATP6V1C2 as a novel candidate gene for recessive distal renal tubular acidosis. Kidney Int. 2020;97:567–79.

    PubMed  CAS  Google Scholar 

  14. Enerbäck S, Nilsson D, Edwards N, et al. Acidosis and deafness in patients with recessive mutations in FOXI1. J Am Soc Nephrol. 2018;29:1041–8.

    PubMed  Google Scholar 

  15. Batlle D, Arruda J. Hyperkalemic forms of renal tubular acidosis: clinical and pathophysiological aspects. Adv Chronic Kidney Dis. 2018;25:321–33.

    PubMed  Google Scholar 

  16. Batlle D, Moorthi KM, Schlueter W, Kurtzman N. Distal renal tubular acidosis and the potassium enigma. Semin Nephrol. 2006;26:471–8.

    PubMed  CAS  Google Scholar 

  17. Strife CF, Clardy CW, Varade WS, Prada AL, Waldo FB. Urine-to-blood carbon dioxide tension gradient and maximal depression of urinary pH to distinguish rate-dependent from classic distal renal tubular acidosis in children. J Pediatr. 1993;122:60–5.

    PubMed  CAS  Google Scholar 

  18. Kim S, Lee JW, Park J, et al. The urine-blood PCO2 gradient as a diagnostic index of H+-ATPase defect distal renal tubular acidosis. Kidney Int. 2004;66:761–7.

    PubMed  CAS  Google Scholar 

  19. Alexander RT, Cordat E, Chambrey R, Dimke H, Eladari D. Acidosis and urinary calcium excretion: insights from genetic disorders. J Am Soc Nephrol. 2016;27:3511–20.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. Hamm LL. Renal handling of citrate. Kidney Int. 1990;38:728–35.

    PubMed  CAS  Google Scholar 

  21. Fuster DG, Moe OW. Incomplete distal renal tubular acidosis and kidney stones. Adv Chronic Kidney Dis. 2018;25:366–74.

    PubMed  Google Scholar 

  22. Alonso-Varela M, Gil-Peña H, Santos F. Incomplete distal renal tubular acidosis in children. Acta Paediatr. 2020. https://doi.org/10.1111/apa.15269.

  23. Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004;24:272.

    PubMed  Google Scholar 

  24. Gupta S, Gao JJ, Emmett M, Fenves AZ. Topiramate and metabolic acidosis: an evolving story. Hosp Pract (1995). 2017;45:192–5.

    Google Scholar 

  25. Besouw MTP, Bienias M, Walsh P, et al. Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol. 2017;32:987–96.

    PubMed  Google Scholar 

  26. Gopal-Kothandapani JS, Doshi AB, Smith K, et al. Phenotypic diversity and correlation with the genotypes of pseudohypoaldosteronism type 1. J Pediatr Endocrinol Metab. 2019;32:959–67.

    PubMed  CAS  Google Scholar 

  27. Mabillard H, Sayer JA. The molecular genetics of Gordon syndrome. Genes (Basel). 2019;10:986.

    CAS  Google Scholar 

  28. Bökenkamp A, Ludwig M. The oculocerebrorenal syndrome of Lowe: an update. Pediatr Nephrol. 2016;31:2201–12.

    PubMed  PubMed Central  Google Scholar 

  29. Watanabe T. Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. Pediatric Health Med Ther. 2018;9:181–90.

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Park E, Cho MH, Hyun HS, et al. Genotype-phenotype analysis in pediatric patients with distal renal tubular acidosis. Kidney Blood Press Res. 2018;43:513–21.

    PubMed  CAS  Google Scholar 

  31. Uduman J, Yee J. Pseudo-renal tubular acidosis: Conditions mimicking renal tubular acidosis. Adv Chronic Kidney Dis. 2018;25:358–65.

    PubMed  Google Scholar 

  32. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2:162–74.

    PubMed  CAS  Google Scholar 

  33. Winter SD, Pearson JR, Gabow PA, Schultz AL, Lepoff RB. The fall of the serum anion gap. Arch Intern Med. 1990;150:311–3.

    PubMed  CAS  Google Scholar 

  34. Batlle D, Ba Aqeel SH, Marquez A. The urine anion gap in context. Clin J Am Soc Nephrol. 2018;13:195–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Batlle D, Chin-Theodorou J, Tucker BM. Metabolic acidosis or respiratory alkalosis? Evaluation of a low plasma bicarbonate using the urine anion gap. Am J Kidney Dis. 2017;70:440–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Palmer BF, Clegg DJ. The use of selected urine chemistries in the diagnosis of kidney disorders. Clin J Am Soc Nephrol. 2019;14:306–16.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Elkinton JR, Huth EJ, Webster GD Jr, McCance RA. The renal excretion of hydrogen ion in renal tubular acidosis. I. Quantitative assessment of the response to ammonium chloride as an acid load. Am J Med. 1960;29:554–75.

    PubMed  CAS  Google Scholar 

  38. Batlle D, Grupp M, Gaviria M, Kurtzman NA. Distal renal tubular acidosis with intact capacity to lower urinary pH. Am J Med. 1982;72:751–8.

    PubMed  CAS  Google Scholar 

  39. Batlle DC. Segmental characterization of defects in collecting tubule acidification. Kidney Int. 1986;30:546–54.

    PubMed  CAS  Google Scholar 

  40. Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet. 1975;2:309–10.

    PubMed  CAS  Google Scholar 

  41. Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012;97:696–706.

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Choi MJ, Ziyadeh FN. The utility of the transtubular potassium gradient in the evaluation of hyperkalemia. J Am Soc Nephrol. 2008;19:424–6.

    PubMed  CAS  Google Scholar 

  43. Walsh SB, Shirley DG, Wrong OM, Unwin RJ. Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride. Kidney Int. 2007;71:1310–6.

    PubMed  CAS  Google Scholar 

  44. Shavit L, Chen L, Ahmed F, et al. Selective screening for distal renal tubular acidosis in recurrent kidney stone formers: initial experience and comparison of the simultaneous furosemide and fludrocortisone test with the short ammonium chloride test. Nephrol Dial Transplant. 2016;31:1870–6.

    PubMed  CAS  Google Scholar 

  45. Palazzo V, Provenzano A, Becherucci F, et al. The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis. Kidney Int. 2017;91:1243–55.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Arvind Bagga & Aditi Sinha

Authors
  1. Arvind Bagga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aditi Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arvind Bagga.

Ethics declarations

Conflict of Interest

None.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bagga, A., Sinha, A. Renal Tubular Acidosis. Indian J Pediatr 87, 733–744 (2020). https://doi.org/10.1007/s12098-020-03318-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-020-03318-8

Keywords

Search

Navigation