Patients with renal tubular acidosis (RTA) have a low arterial pH and low serum bicarbonate with hyperchloraemia and a normal serum anion gap.
Inherited (primary) classic distal RTA (type I) most often results from mutations of the genes for the renal apical membrane H-ATPase proton pump or the basolateral membrane anion exchanger AE1 gene.
The urine pH exceeds 5.5 in classic distal RTA, but is less than 5.0 in patients with untreated proximal RTA. Urine pH is also low in hyperkalaemic distal RTA.
Proximal RTA (type II) occurs most often as a component of Fanconi syndrome, which is characterised by generalised dysfunction of the proximal tubule, with the resultant urinary loss of bicarbonate, calcium, phosphate, urate, amino acids, glucose, and other organic acids and bases.
Type III is a combination of proximal and distal RTA. Carbonic anhydrase II deficiency and carbonic anhydrase inhibitors block intracellular metabolism of bicarbonate and carbonic acid.
Defining characteristics of hyperkalaemic (type IV) distal RTA are clinically significant hyperkalaemia and the absence of the normal negative urine anion gap.
Adult patients with RTA are often asymptomatic but may present with muscular weakness related to associated hypokalaemia, nephrocalcinosis, or recurrent renal stones.
Alkali therapy is the mainstay of treatment in all forms of RTA.
If hyperkalaemic distal RTA is due to mineralocorticoid deficiency, fludrocortisone can be given unless it is contraindicated due to the presence of fluid overload or uncontrolled hypertension.
Correction of the hyperkalaemia in hyperkalaemic distal RTA often improves both urinary acidification and metabolic acidosis.
The term renal tubular acidosis (RTA) describes any one of a number of disorders, in which the excretion of fixed acid (distal RTA) or the reabsorption of filtered bicarbonate (proximal RTA) is impaired to a degree that is disproportionate to any existing impairment of the glomerular filtration rate. The acid retention or bicarbonate loss results in the development of hyperchloraemic metabolic acidosis marked by hypobicarbonataemia and depressed arterial blood pH. In the absence of other acid-base disorders the serum anion gap is normal. Either hypokalaemia or hyperkalaemia may be present, depending on the nature of the acidification defect.
Fanconi syndrome is characterised by a generalised dysfunction of the renal proximal tubule that results in the urinary loss of substances normally reabsorbed by the kidney at this site. The substrates lost include bicarbonate, glucose, amino acids, phosphate, small proteins and peptides, and organic acids and bases. Salt wasting, volume depletion, and potassium wasting often develop as secondary effects. The pathophysiological basis of these abnormalities depends upon the specific cause of the individual patient’s Fanconi syndrome.
History and exam
- sensorineural hearing loss
- liver dysfunction
- osteopenia, osteopetrosis, nephrocalcinosis, and cerebral calcifications
- Kussmaul's breathing
- ocular abnormalities (cataracts, glaucoma, band keratopathy), growth retardation, impaired intellect, calcification of basal ganglia
- urinary tract obstruction
- diabetes mellitus
- primary biliary cirrhosis
- amphotericin-B therapy
- toxic exposure to heavy metals, and cis-platinum
- untreated adrenal insufficiency
- environmental exposure in the Balkans
- older men
- family history of inherited RTA
- hereditary fructose intolerance
- Wilson's disease
- disorders of mitochondrial metabolism
- glycogen storage diseases
- Lowe's syndrome
- lead exposure
- cadmium exposure
- ifosfamide therapy
- 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
- Thai or southeast Asian ancestry
- outdated tetracycline
- cis-platinum therapy
- toluene, paraquat, lysol exposure
- Balkan heritage
- Dent's disease
- ibuprofen overdose
- antiviral therapy (cidofovir, adefovir, or tenofovir)
- 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
- CT/spiral CT
- nuclear renal scan
Melvin E. Laski, MD
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 topic.
EC and AK declare that they have no competing interests; RT's competing interests are not disclosed.
Daniel Batlle, MD
DB declares that he has no competing interests.
Troels Ring, MD
Department of Nephrology
TR declares that he has no competing interests.
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