Types of Renal Tubular Acidosis (RTA)
There are four main types of RTA, classified by the location and mechanism of tubular dysfunction: Type 1 (distal), Type 2 (proximal), Type 3 (mixed/rare), and Type 4 (hyperkalemic). 1, 2
Type 1 RTA (Distal RTA)
Type 1 RTA results from impaired hydrogen ion secretion in the distal tubule and collecting duct, leading to inability to acidify urine below pH 5.5 despite systemic acidosis. 1, 3, 4
Key clinical features:
- Normal anion gap metabolic acidosis with positive urine anion gap (indicating impaired NH4+ excretion) 5, 2
- Severe hypokalemia that can cause paralysis, rhabdomyolysis, cardiac arrhythmias, and sudden death 6, 5
- Hypercalciuria leading to nephrocalcinosis and nephrolithiasis due to alkaline urine and low urinary citrate 5
- Inability to lower urine pH below 5.5 even during severe acidosis 4
Presentation patterns:
- Primary/inherited forms typically diagnosed in infancy, childhood, or young adulthood 4
- Secondary/acquired forms can occur at any age, more commonly in adults 4
Type 2 RTA (Proximal RTA)
Type 2 RTA is caused by defective bicarbonate reabsorption in the proximal tubule, with fractional excretion of bicarbonate exceeding 15% during bicarbonate loading. 1, 3
Key clinical features:
- Normal anion gap metabolic acidosis with negative urine anion gap (preserved distal acidification) 2
- Associated Fanconi syndrome features including aminoaciduria, glucosuria, phosphaturia, and uricosuria 6, 5
- Rickets in children due to phosphate wasting 5
- Can acidify urine to pH <5.5 once plasma bicarbonate falls below reabsorptive threshold 3
Important distinction: The fractional excretion of bicarbonate during bicarbonate loading helps confirm Type 2 RTA, as recommended by the European Renal Association 5
Type 3 RTA (Mixed/Rare)
Type 3 RTA is an extremely rare form combining features of both distal and proximal RTA. 1 This classification is largely historical and rarely used in current clinical practice, as most cases previously labeled Type 3 are now recognized as severe forms of Type 1 or combined defects. 7
Type 4 RTA (Hyperkalemic RTA)
Type 4 RTA results from aldosterone deficiency or resistance, causing abnormal excretion of both acid and potassium in the collecting duct. 1, 7
Key clinical features:
- Hyperkalemia is the dominant and distinguishing feature 5
- Mild metabolic acidosis with normal anion gap 5
- Risk of cardiac arrhythmias from hyperkalemia 5
- Commonly seen in chronic kidney disease stages 3-5, as noted by the American College of Physicians 5
Diagnostic approach: Confirm selective aldosterone deficiency or resistance after excluding other causes of hyperkalemia 1
Diagnostic Algorithm
Step 1: Confirm normal anion gap (8-12 mEq/L) metabolic acidosis to distinguish from high anion gap acidoses 5, 2
Step 2: Check serum potassium:
Step 3: Calculate urine anion gap (Na+ + K+ - Cl-):
- Positive (Cl- < Na+ + K+) → Distal acidification defect (Type 1) 5, 2
- Negative (Cl- >> Na+ + K+) → Proximal defect or GI bicarbonate loss (Type 2) 2
Step 4: Assess urine pH at low plasma bicarbonate:
Step 5: If Type 2 suspected, measure fractional excretion of bicarbonate during bicarbonate loading (>15% confirms Type 2) 5, 3
Critical Pitfalls to Avoid
Do not confuse RTA with Bartter syndrome, which presents with hypokalemic metabolic alkalosis (not acidosis) and elevated fractional chloride excretion (>0.5%), as cautioned by the International Society of Nephrology 5
Avoid obsolete and dangerous diagnostic tests including loop diuretic/thiazide tubular function testing and ammonium chloride loading tests, which risk severe volume depletion (especially in infants) and worsening acidosis 5
Never use thiazide diuretics for hypercalciuria management in Type 1 RTA patients, as they worsen hypokalemia 6
Avoid potassium-sparing diuretics, ACE inhibitors, and ARBs as routine therapy in Type 4 RTA due to risk of dangerous hyperkalemia 6