Last reviewed:September 2019
Last updated:October  2017



History and exam

Key diagnostic factors

  • presence of risk factors
  • growth retardation
  • muscular weakness
  • failure to thrive (children)
  • hypoglycaemia after fructose ingestion
  • rickets
  • ethnicity/national origin
  • nephrolithiasis

Other diagnostic factors

  • deafness
  • liver dysfunction
  • osteopenia, osteopetrosis, nephrocalcinosis, and cerebral calcifications
  • nephrocalcinosis
  • Kussmaul's breathing
  • ocular abnormalities (cataracts, glaucoma, band keratopathy), growth retardation, impaired intellect, calcification of basal ganglia

Risk factors

  • childhood
  • urinary tract obstruction
  • diabetes mellitus
  • primary biliary cirrhosis
  • nephrocalcinosis
  • nephrolithiasis
  • amphotericin-B therapy
  • toxic exposure to heavy metals, and cis-platinum
  • untreated adrenal insufficiency
  • environmental exposure in the Balkans
  • older men
  • FHx inherited RTA without deafness
  • FHx inherited RTA with deafness
  • hereditary fructose intolerance
  • Wilson's disease
  • galactosaemia
  • disorders of mitochondrial metabolism
  • glycogen storage diseases
  • tyrosinaemia
  • Lowe's syndrome
  • lead exposure
  • cadmium exposure
  • ifosfamide therapy
  • cystinosis
  • cyclosporine therapy
  • angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocking drugs
  • heparin therapy
  • medications interfering with sodium transport
  • use of carbonic anhydrase inhibitors
  • abnormalities of filtered immunoglobulins
  • interstitial nephritis
  • hyperparathyroidism
  • Thai or southeast Asian ancestry
  • outdated tetracycline
  • cis-platinum therapy
  • toluene, paraquat, lysol exposure
  • Balkan heritage
  • Dent's disease
  • ibuprofen overdose
  • lamivudine
  • antiviral therapy (cidofovir, adefovir, or tenofovir)

Diagnostic investigations

1st investigations to order

  • serum bicarbonate
  • serum chloride
  • serum sodium
  • serum potassium
  • arterial blood pH
  • serum anion gap
  • urine pH
Full details

Investigations to consider

  • serum aldosterone
  • urine anion gap
  • measurement of fractional bicarbonate excretion
  • urine PCO2 bicarbonate infusion
  • furosemide test
  • ammonium chloride loading test
  • furosemide and fludrocortisone test
  • urine glucose
  • tubular maximum (Tm) reabsorption of phosphate
  • fractional excretion of amino acids
  • ultrasound
  • CT/spiral CT
  • nuclear renal scan
Full details

Treatment algorithm


Professor Emeritus

Texas Tech University Health Sciences Center




MEL declares that he has no competing interests.

Dr Melvin E. Laski would like to gratefully acknowledge Dr Elizabeth Cobb, Dr Rebin Titus, and Dr Abeer Kaldas, previous contributors to this monograph. EC and AK declare that they have no competing interests; RT's competing interests are not disclosed.

Peer reviewersVIEW ALL


Northwestern University




DB declares that he has no competing interests.

Department of Nephrology

Aalborg Hospital




TR declares that he has no competing interests.

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