What is Renal Tubular Acidosis (RTA)?

Renal Tubular Acidosis (RTA)

Renal tubular acidosis is a group of disorders characterized by impaired renal acid-base regulation resulting in normal anion gap metabolic acidosis, with specific types distinguished by the location of tubular dysfunction and associated electrolyte abnormalities.

Types of RTA

Type 1 (Distal) RTA

• Definition: Impaired acid secretion in the distal nephron
• Key features:
  • Inability to acidify urine (urine pH >5.5 despite acidosis)
  • Hypokalemia
  • Hypercalciuria leading to nephrocalcinosis/nephrolithiasis
  • Metabolic bone disease (rickets, osteomalacia)
• Causes:
  • Primary (genetic): Mutations affecting H⁺-ATPase or anion exchanger proteins
  • Secondary: Autoimmune diseases, medications, hypercalciuria 1

Type 2 (Proximal) RTA

• Definition: Defective bicarbonate reabsorption in the proximal tubule
• Key features:
  • Bicarbonate wasting in urine
  • Hypokalemia
  • Often part of generalized proximal tubular dysfunction (Fanconi syndrome)
• Causes:
  • Primary (genetic): Mutations in carbonic anhydrase II or other transporters
  • Secondary: Medications, heavy metals, multiple myeloma 2

Type 4 (Hyperkalemic) RTA

• Definition: Abnormal acid and potassium excretion in the collecting duct
• Key features:
  • Hyperkalemia
  • Mild metabolic acidosis
  • Normal or slightly elevated urine pH
• Causes:
  • Hypoaldosteronism
  • Aldosterone resistance
  • Medications (ACE inhibitors, NSAIDs, potassium-sparing diuretics) 2

Type 3 RTA

• Rare combined form with features of both distal and proximal RTA 2

Clinical Manifestations

Metabolic Consequences

• Chronic metabolic acidosis
• Electrolyte disturbances (hypokalemia or hyperkalemia)
• Growth retardation in children
• Rickets or osteomalacia due to bone buffering of acid 3

Renal Manifestations

• Nephrocalcinosis (especially in Type 1 RTA)
• Nephrolithiasis
• Progressive kidney injury if untreated 4

Systemic Manifestations

• Failure to thrive in children
• Muscle weakness (from hypokalemia)
• Bone pain and fractures
• Polyuria and polydipsia 5

Diagnosis

Laboratory Evaluation

• Normal anion gap metabolic acidosis
• Serum electrolytes (potassium abnormalities)
• Urinary pH:
  • Type 1: Persistently >5.5 despite acidosis
  • Type 2: Variable, can acidify when serum bicarbonate is low
  • Type 4: Usually <5.5
• Urinary anion gap to assess ammonia excretion
• Fractional excretion of bicarbonate (elevated in Type 2)

Imaging

• Renal ultrasound to detect nephrocalcinosis/nephrolithiasis
• Bone imaging for evidence of rickets or osteomalacia 6

Specialized Testing

• Urine acidification tests (ammonium chloride loading)
• Genetic testing for hereditary forms 6

Treatment

Type 1 (Distal) RTA

• Alkali therapy: Potassium citrate (preferred in RTA with calcium stones) 7
  • Dosage: 1-2 mEq/kg/day divided 2-3 times daily
  • Goal: Normalize serum bicarbonate and urinary citrate
• Monitor serum electrolytes, urinary citrate, and pH every four months 7

Type 2 (Proximal) RTA

• Alkali therapy: Higher doses often required (5-15 mEq/kg/day)
• Potassium supplementation for hypokalemia
• Treatment of underlying cause when possible

Type 4 (Hyperkalemic) RTA

• Dietary potassium restriction
• Fludrocortisone if hypoaldosteronism present
• Discontinuation of medications causing hyperkalemia
• Potassium binders for persistent hyperkalemia 2

Monitoring and Follow-up

• Regular assessment of acid-base status
• Monitoring of electrolytes (especially potassium)
• Renal function tests
• Urinary parameters (pH, citrate)
• Imaging for nephrocalcinosis/nephrolithiasis 6

Complications of Untreated RTA

• Growth failure in children
• Progressive bone disease (osteomalacia, rickets)
• Nephrocalcinosis and kidney stones
• Progressive kidney injury
• Muscle weakness and fatigue 3

Special Considerations

• In patients with hereditary tyrosinemia type 1, RTA can be reversed with NTBC (nitisinone) treatment 6
• Complete normalization of plasma potassium may not be necessary or achievable in some forms of RTA 6
• Avoid potassium citrate in patients with hyperkalemic (Type 4) RTA

RTA is not a benign condition as previously thought, and early diagnosis and appropriate treatment are essential to prevent long-term complications affecting growth, bone health, and kidney function.