Renal tubular acidosis (RTA) is a clinical syndrome characterized by hyperchloremic metabolic acidosis with a normal serum anion gap.
Adult patients with RTA are often asymptomatic but may present with muscular weakness related to associated hypokalemia, nephrocalcinosis, or recurrent renal stones.
There are four types of RTA: classic distal RTA (type I), proximal RTA (type II), hyperkalemic distal RTA (type IV), and a rare combination of proximal and distal RTA caused by carbonic anhydrase II deficiency and carbonic anhydrase inhibitors blocking the metabolism of bicarbonate and carbonic acid (type III).
Alkali therapy is the mainstay of treatment in all forms of RTA.
If hyperkalemic 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.
The term renal tubular acidosis (RTA) describes a group of disorders of acid-base homeostasis, in which the primary impairment is the excretion of fixed acid (distal RTA) or the reabsorption of filtered bicarbonate (proximal RTA). The acid retention or bicarbonate loss results in hyperchloremic metabolic acidosis marked by low serum bicarbonate and a normal anion gap. Either hypokalemia or hyperkalemia may be present, depending on the nature of the acidification defect.
Fanconi syndrome is due to dysfunction of the renal proximal tubule resulting in the urinary loss of substances normally reabsorbed by the kidney at this site, such as bicarbonate, glucose, amino acids, phosphate, small proteins, and uric acid. Salt wasting, volume depletion, and potassium wasting often develop as secondary effects. The pathophysiologic 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 breathing
- ocular abnormalities (cataracts, glaucoma, band keratopathy), growth retardation, impaired intellect, and calcification of basal ganglia
- urinary tract obstruction
- diabetes mellitus
- primary biliary cirrhosis
- amphotericin-B therapy
- toxic exposure to heavy metals, and cis-platinum
- untreated primary adrenal insufficiency
- family history of inherited RTA
- older men
- hereditary fructose intolerance
- Wilson disease
- disorders of mitochondrial metabolism
- glycogen storage diseases
- Lowe 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
- environmental exposure to aristolochic acid
- Thai or southeast Asian ancestry
- cis-platinum therapy
- toluene, paraquat, lysol exposure
- Dent disease
- ibuprofen overdose
- antiviral therapy (cidofovir, adefovir, or tenofovir)
- programmed cell death protein 1 (PD-1)-inhibitors
- 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
Ashish Verma, MBBS
Assistant Professor of Medicine
Section of Nephrology
Department of Medicine
Boston University School of Medicine/Boston Medical Center
AV declares that he has no competing interests.
Dr Ashish Verma would like to gratefully acknowledge Dr Melvin E. Laski, Dr Elizabeth Cobb, Dr Rebin Titus, and Dr Abeer Kaldas, previous contributors to this topic.
MEL, 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.
Use of this content is subject to our disclaimer