Renal tubular acidosis

Definition

• Group of diseases characterized by non-anion gap metabolic acidosis and preserved renal function

Types

Type I: hypokalemic distal

• Caused by defects in distal tubular H+ secretion
• Hypokalemia, positive urine anion gap, urine pH >5.5
• Etiology
  • Hereditary
  • Genetic: sickle cell; Fabry disease; Wilson disease; elliptocytosis
  • Medullary cystic kidney disease
  • Autoimmune: Sjögren syndrome, systemic lupus erythematosus
  • Nephrocalcinosis/hypercaliuria
  • Dysproteinemias: amyloidosis, cryoglobulinemia, hypergammaglobulinemia
  • Drugs: amphotericin B, lithium, analgesic abuse
  • Tubulointerstitial disease: reflux nephropathy, obstrctive uropathy, kidney transplant rejection

Type II: proximal

• Caused by proximal tubular bicarbonate reabsorption
• Hypokalemia, negative urine anion gap, urine pH variable
• Etiology
  • Primary (hereditary or sporadic)
  • Hereditary carbonic anhydrase deficiency
  • Fanconi syndrome

Type IV: hyperkalemic distal

• Caused by impaired ammoniagenesis, often caused by hypoaldosteronism
• Hyperkalemia, positive urine anion gap, urine pH <5.5
• Etiology
  • Primary aldosterone deficiency (Addison disease)
  • Hyporeninemic hypoaldosteronism
    • Acute glomerulonephritis
    • Chronic nephropathy
      • Diabetes (most common cause)
      • Systemic lupus erythematosus
      • AIDS
  • Aldosterone resistance:
    • Tubulointerstitial disease: urinary obstruction, sickle cell disease, medullary cystic kidney disease, and kidney transplant rejection
  • Drugs: ACE inhibitors, cyclooxygenase inhibitors, trimethoprim, heparin
• Mixed proximal/distal
  • Carbonic anhydrase mutations
  • Drugs: topiramate

Risk Factors

• Type IV: diabetes

Investigations

• Serum electrolytes
  • Normal anion gap metabolic acidosis
  • Hyperkalemia (type IV)
• Urine anion gap: UNa + UK - UCl
  • If positive, suggests presence of ammonium
  • If kidneys are responding properly, the UAG should be negative
  • If defect in acid excretion, UAG should be positive
• Urine pH

	Type 1	Type 2	Type 4
Acidosis	Severe	Moderate	Mild
Serum K	↓ / ↑*	↓	↑
Serum HCO3	Variable	10-20	>17
Urine pH	>5.3	<5.3	<5.3
Urine AG	+	±	+

• a hyperkalemic Type 1 RTA is possible with urinary obstruction, sickle cell, lupus, and renal transplant