Renal Tubular Acidosis: Types and Mechanisms
Overview
Renal tubular acidosis (RTA) comprises three major types distinguished by their underlying tubular defects: Type 1 (distal RTA) results from impaired distal acid excretion, Type 2 (proximal RTA) from defective proximal bicarbonate reabsorption, and Type 4 (hyperkalemic RTA) from aldosterone deficiency or resistance affecting the collecting duct. 1, 2
All RTA types present with normal anion gap (8-12 mEq/L) hyperchloremic metabolic acidosis, distinguishing them from high anion gap acidoses like diabetic ketoacidosis. 1, 3
Type 1 RTA (Distal RTA)
Mechanism
- Primary defect: Impaired hydrogen ion secretion in the distal tubule and collecting duct, preventing urine acidification below pH 5.5 even during severe acidosis 2, 4
- The inability to excrete acid leads to systemic acidosis with inappropriately alkaline urine 3, 5
Clinical Features
- Severe hypokalemia is characteristic and can cause paralysis, rhabdomyolysis, cardiac arrhythmias, and sudden death 1, 6
- Nephrocalcinosis and nephrolithiasis develop commonly due to hypercalciuria, persistently alkaline urine (pH >5.5), and low urinary citrate 1
- Normal anion gap metabolic acidosis with positive urine anion gap (indicating impaired NH4+ excretion) 1, 3
Diagnostic Approach
- Urine pH remains >5.5 despite systemic acidosis 3, 5
- Positive urine anion gap (Cl- < Na+ + K+) indicates defective distal acidification 3
- Elevated urine calcium levels confirm hypercalciuria 1
- Avoid the obsolete and dangerous ammonium chloride loading test, especially in patients with pre-existing severe acidosis 1
Type 2 RTA (Proximal RTA)
Mechanism
- Primary defect: Impaired bicarbonate reabsorption in the proximal tubule, with fractional excretion of bicarbonate >15% during bicarbonate loading 2, 3
- Once plasma bicarbonate falls below the reduced reabsorptive threshold, distal tubule can acidify urine normally (pH <5.5) 4, 5
Clinical Features
- Fanconi syndrome features frequently present: aminoaciduria, glucosuria, phosphaturia, and uricosuria 1, 6
- Rickets in children due to phosphate wasting 1, 6
- Normal anion gap metabolic acidosis with negative urine anion gap (when plasma bicarbonate is low) 1, 3
- Hypokalemia develops but is typically less severe than Type 1 RTA 4
Diagnostic Approach
- Fractional excretion of bicarbonate >15% during bicarbonate loading confirms the diagnosis 1, 3
- Urine pH can be <5.5 when plasma bicarbonate is reduced below the reabsorptive threshold 3, 5
- Assess for associated Fanconi syndrome components 5, 7
Type 4 RTA (Hyperkalemic RTA)
Mechanism
- Primary defect: Aldosterone deficiency or resistance in the collecting duct, causing impaired potassium and hydrogen ion excretion 2, 4
- Hyperkalemia suppresses ammonia production, further limiting acid excretion 4, 3
Clinical Features
- Hyperkalemia is the dominant and distinguishing feature, with risk of life-threatening cardiac arrhythmias 1, 6
- Mild metabolic acidosis with normal anion gap 1
- Consider Type 4 RTA in adults with chronic kidney disease stages 3-5 presenting with hyperkalemia 1
Diagnostic Approach
- Confirm hyperkalemia with mild metabolic acidosis 1, 2
- Exclude other causes of hyperkalemia before diagnosing aldosterone deficiency or resistance 2
- Urine pH typically <5.5 (distal acidification intact) 4
Critical Diagnostic Distinctions
Urine Anion Gap Interpretation
- Positive urine anion gap (Cl- < Na+ + K+): Indicates Type 1 RTA with impaired NH4+ excretion 1, 3
- Negative urine anion gap (Cl- >> Na+ + K+): Suggests gastrointestinal bicarbonate loss or Type 2 RTA (when bicarbonate is low) 3
Avoiding Diagnostic Pitfalls
- Do not confuse RTA with Bartter syndrome, which presents with hypokalemic metabolic alkalosis (not acidosis) and elevated fractional chloride excretion >0.5% 1
- Avoid routine tubular function testing with loop diuretics or thiazides, as these obsolete tests have uncertain diagnostic value and risk severe volume depletion, especially in infants 1
- Chronic urinary obstruction can silently cause tubular dysfunction and RTA; do not assume obstruction only causes acute kidney injury 1
Type 3 RTA (Rare Mixed Form)
Type 3 RTA is an extremely rare variant with features of both proximal and distal RTA, now considered largely of historical interest. 2, 4