What is Renal Tubular Acidosis (RTA)?
Renal tubular acidosis (RTA) is a group of kidney disorders characterized by the inability to maintain normal acid-base balance due to defective tubular handling of hydrogen ions or bicarbonate, resulting in a normal anion gap (8-12 mEq/L) metabolic acidosis despite preserved glomerular filtration rate. 1, 2, 3
Core Pathophysiology
RTA occurs when specific tubular transport mechanisms fail, preventing either:
The hallmark laboratory finding across all RTA types is normal anion gap metabolic acidosis, which distinguishes RTA from high anion gap acidoses like diabetic ketoacidosis 1, 4
Three Major Clinical Types
Type 1 (Distal) RTA
- Defect: Impaired hydrogen ion secretion in the distal tubule/collecting duct 2, 5
- Key features: Severe hypokalemia (can cause paralysis, rhabdomyolysis, cardiac arrhythmias), inability to acidify urine below pH 5.5, positive urine anion gap 1, 5
- Complications: Nephrocalcinosis, kidney stones, hypercalciuria, bone disease 1, 5
- Genetics: Mutations in SLC4A1 (autosomal dominant) or ATP6V0A4/ATP6V1B1 (autosomal recessive with hearing loss) 1
Type 2 (Proximal) RTA
- Defect: Impaired bicarbonate reabsorption in the proximal tubule 6, 2
- Key features: Part of Fanconi syndrome with aminoaciduria, glucosuria (despite normal serum glucose), phosphaturia, hypokalemia, hypophosphatemia 1, 6
- Complications: Rickets in children from phosphate wasting, osteomalacia, bone pain 1, 6
- Urine findings: Negative urine anion gap, can acidify urine when bicarbonate depleted 1
Type 4 (Hyperkalemic) RTA
- Defect: Aldosterone deficiency or resistance affecting the collecting duct 2, 7
- Key features: Hyperkalemia is the dominant distinguishing feature (not hypokalemia like Types 1 and 2), mild metabolic acidosis 1, 2
- Risk: Cardiac arrhythmias from elevated potassium 1
- Common in: Chronic kidney disease stages 3-5, diabetes, medications (ACE inhibitors, ARBs, potassium-sparing diuretics) 1, 8
Clinical Presentation Patterns
Pediatric presentation typically includes failure to thrive, growth retardation, polyuria, vomiting, dehydration, rickets, and hypotonia 5, 4
Adult presentation often involves weakness from hypokalemia (Types 1-2), bone pain, kidney stones, or is discovered incidentally during evaluation of chronic metabolic acidosis 5, 4
Diagnostic Approach
Calculate the anion gap first: Normal (8-12 mEq/L) confirms RTA as a possibility 1
Serum potassium then differentiates the types:
Urine pH and anion gap distinguish Type 1 from Type 2:
- Type 1: Urine pH persistently >5.5, positive urine anion gap 1
- Type 2: Can acidify urine <5.5 when bicarbonate depleted, negative urine anion gap 1
Additional testing includes urine calcium (elevated in Type 1), renal ultrasound (nephrocalcinosis in Type 1), and assessment for Fanconi syndrome features (Type 2) 1, 6
Treatment Principles
Type 1 RTA: Potassium citrate is first-line therapy (1-2 mEq/kg/day divided 3-4 times daily), simultaneously correcting acidosis and hypokalemia; target serum bicarbonate >22 mEq/L in adults and potassium ≥3.0 mmol/L 1, 8
Type 2 RTA: Requires higher alkali doses due to bicarbonate wasting, plus phosphate supplementation and vitamin D for rickets/bone disease 8, 6
Type 4 RTA: Focus on lowering potassium through dietary restriction and treating underlying cause; alkali therapy only if bicarbonate <18 mmol/L 8
Critical Management Pitfalls
Avoid thiazide diuretics in Type 1 RTA (worsen hypokalemia) 8
Avoid potassium-sparing diuretics, ACE inhibitors, and ARBs in Type 4 RTA (dangerous hyperkalemia) 8
Never use obsolete tubular function tests with loop diuretics or thiazides (risk severe volume depletion) 1
Monitor electrolytes every 2-4 weeks initially, then every 3-6 months when stable; perform annual renal ultrasound in Type 1 RTA to track nephrocalcinosis 1