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Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis.
J Nephrol 2018; 31(4):511-522JN

Abstract

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.

Authors+Show Affiliations

Division of Nephrology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland. nilufar.mohebbi@usz.ch. National Center for Competence in Research NCCR Kidney.CH, Zurich, Switzerland. nilufar.mohebbi@usz.ch.National Center for Competence in Research NCCR Kidney.CH, Zurich, Switzerland. Wagnerca@access.uzh.ch. Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. Wagnerca@access.uzh.ch.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

28994037

Citation

Mohebbi, Nilufar, and Carsten A. Wagner. "Pathophysiology, Diagnosis and Treatment of Inherited Distal Renal Tubular Acidosis." Journal of Nephrology, vol. 31, no. 4, 2018, pp. 511-522.
Mohebbi N, Wagner CA. Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. J Nephrol. 2018;31(4):511-522.
Mohebbi, N., & Wagner, C. A. (2018). Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. Journal of Nephrology, 31(4), pp. 511-522. doi:10.1007/s40620-017-0447-1.
Mohebbi N, Wagner CA. Pathophysiology, Diagnosis and Treatment of Inherited Distal Renal Tubular Acidosis. J Nephrol. 2018;31(4):511-522. PubMed PMID: 28994037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. AU - Mohebbi,Nilufar, AU - Wagner,Carsten A, Y1 - 2017/10/09/ PY - 2017/06/28/received PY - 2017/09/21/accepted PY - 2017/10/11/pubmed PY - 2019/7/26/medline PY - 2017/10/11/entrez KW - Alkali KW - Hearing loss KW - Hypokalemia KW - Mutation KW - Nephrocalcinosis KW - Proton pump SP - 511 EP - 522 JF - Journal of nephrology JO - J. Nephrol. VL - 31 IS - 4 N2 - 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. SN - 1724-6059 UR - https://www.unboundmedicine.com/medline/citation/28994037/Pathophysiology_diagnosis_and_treatment_of_inherited_distal_renal_tubular_acidosis_ L2 - https://dx.doi.org/10.1007/s40620-017-0447-1 DB - PRIME DP - Unbound Medicine ER -