Overview
Renal tubular acidosis (RTA) describes a group of disorders leading to hyperchloraemic metabolic acidosis with a normal ion gap. There are 4 types:
- Type I (classic distal) RTA
- Type II (proximal) RTA
- Type III (combined proximal and distal) RTA – rare
- Type IV (hyperkalaemic distal) RTA
RTA can also occur due to CKD progressing.
Epidemiology
- All forms of RTA are generally uncommon, but RTA is likely under-reported
Type 1 (Distal) RTA
Overview
Type 1 RTA occurs due to a failure of H+ secretion into the nephron lumen by cells in the distal nephron. An inability of H+ secretion also means K+ cannot be reabsorbed and is lost, therefore H+ is retained (leading to acidosis) and hypokalaemia may occur.
Causes and associations
Some causes and associations include:
- Idiopathic
- Associated autoimmune disorders (e.g. systemic lupus erythematosus and Sjögren’s syndrome)
- Hyperparathyroidism
- Renal transplant rejection
- Analgesic nephropathy
Features
Some features include:
- Features of hypokalaemia (e.g. arrhythmia)
- Nephrocalcinosis – deposition of calcium in the kidneys
- Renal stones – due to higher urinary pH (calcium tends to deposit at higher pHs)
- Rickets/osteomalacia – chronic acidosis leeches calcium out of bones
Investigations
Investigations may show:
- Hypokalaemia
- Hyperchloraemic metabolic acidosis with a normal ion gap
- Elevated urinary pH
- Hypercalciuria
Type 2 (Proximal) RTA
Overview
Proximal RTA occurs due to cells in the proximal nephron tubule failing to reabsorb bicarbonate ions from the urine. This leads to a loss of bicarbonate and acidosis as bicarbonate normally acts as a buffer in the blood.
Potassium ions bind to bicarbonate and are lost in the urine along with phosphate.
Causes and associations
Some causes and associations include:
- Idiopathic
- Fanconi’s syndrome
Features
- Hypokalaemia
- Rickets/osteomalacia – due to acidosis and phosphate loss
Investigations
Investigations may show:
- Hypokalaemia
- Hyperchloraemic metabolic acidosis with a normal ion gap
Type 3 (Combined Proximal and Distal) RTA
Overview
Type 3 RTA is extremely rare and occurs due to a deficiency in carbonic anhydrase II, which is essential for converting CO2 and H2O into bicarbonate (HCO3–).
Causes and associations
- Some causes and associations include:
- Inherited
- Iatrogenic (e.g. acetazolamide, a carbonic anhydrase inhibitor)
Features
- Osteopetrosis – abnormally overly dense and brittle bones
- Cerebral calcification
Investigations
Investigations may show:
- Hypokalaemia
- Hyperchloraemic metabolic acidosis with a normal ion gap
Type 4 (Hyperkalaemic) RTA
Overview
Type 4 RTA is technically not an intrinsic tubular disorder. It occurs when hypoaldosteronism is present, leading to reduced proximal tubular ammonium excretion. Aldosterone normally leads to water and Na+ retention and excretes sodium. Therefore, in this type of RTA, patients may have hyperkalaemia instead of hypokalemia.
Causes and associations
Some causes and associations include:
- Hypoaldosteronism (e.g. Addison’s disease)
- Drugs (e.g. ACE inhibitors, aldosterone antagonists such as spironolactone, NSAIDs)
- Diabetes mellitus
Investigations
- Hyperkalaemia
- Normal urinary pH – acidification of urine is unaffected