Journal of Nephrology

, Volume 31, Issue 4, pp 511–522 | Cite as

Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis

  • Nilufar MohebbiEmail author
  • Carsten A. WagnerEmail author


Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are due to mutations in at least three distinct genes: SLC4A1, ATP6V1B1, ATP6V0A4. Mutations in SLC4A1-(AE1) are inherited either in an autosomal dominant manner or in a recessive one. ATP6V1B and ATP6V0A4 mutations affect two different subunits of the vacuolar H+-ATPase proton-pump, the B1 and a4 subunits, and are inherited in an autosomal recessive manner. Clinical manifestations of inherited forms of dRTA usually occur during infancy or childhood. However, heterozygous carriers of ATP6V1B1 and ATP6V0A4 mutations may have a higher risk of developing nephrolithiasis and nephrocalcinosis in adulthood, respectively. In full forms of dRTA, patients may present with mild clinical symptoms, such as mild metabolic acidosis and incidental detection of kidney stones, as well as with more severe manifestations such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. Progressive sensorineural hearing loss develops in the majority of patients with recessive dRTA (ATP6V1B1 and ATP6V0A4 mutations). Some patients with recessive dRTA may also develop abnormal widening of the vestibular aqueduct. This review will discuss our current understanding of the pathophysiology of inherited forms of dRTA, diagnosis and prognosis of patients, and therapy.


Mutation Proton pump Nephrocalcinosis Hearing loss Alkali Hypokalemia 



Work of the authors has been supported by the Swiss National Science Foundation and the 6th and 7th EU Frame work projects Eunefron and Eurenomics.

Compliance with ethical standards

Ethical statement

This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Italian Society of Nephrology 2017

Authors and Affiliations

  1. 1.Division of NephrologyUniversity Hospital ZurichZurichSwitzerland
  2. 2.National Center for Competence in Research NCCR Kidney.CHZurichSwitzerland
  3. 3.Institute of PhysiologyUniversity of ZurichZurichSwitzerland

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