Description

• Characterized by a hyperchloremic, normal anion gap acidosis in the absence of other illness
• GFR is usually normal
• 3 types:
  • Type I:
    • Inability to acidify the urine in the distal kidney
    • Causes a normal anion gap acidosis with hypokalemia
  • Type II:
    • A reduction in the ability for the proximal kidney to reabsorb bicarb
    • Causes a normal anion gap acidosis with hypokalemia
  • Type III:
    • A mix of types I and II
  • Type IV:
    • Reduced excretion of acid and K⁺
    • Causes a normal anion gap acidosis with hyperkalemia

Epidemiology

Incidence and Prevalence Estimates

• Very rare to be diagnosed in adults, although more likely to be acquired
• Rare in children, but more likely primary
• Type III is the rarest
• 20% incidence in renal transplant patients
• Type IV most common in adults in the US given incidence of diabetic nephropathy

Etiology

• Type I:
  • Impairment of distal H+ excretion due to malfunctioning ATPase’s or increased H+ permeability
  • Primary: Genetic defect/mutation
  • Acquired: From nephrotoxic substances including amphotericin B, high-dose ibuprofen, lithium
  • Secondary: Sequelae of another autoimmune disease, commonly Sjögren syndrome
  • Toluene inhalation
• Type II:
  • Defect in reabsorption of bicarb in the proximal tubule
  • Primary: Autosomal recessive
  • Acquired: Carbonic anhydrase inhibitor use
  • Commonly seen with Fanconi syndrome
• Type IV:
  • Aldosterone deficiency or resistance
  • Associated with diabetic nephropathy
  • May be medication induced: K⁺-sparing diuretics (spironolactone), trimethoprim, NSAIDs, ACE inhibitors, heparin, LMWH, tacrolimus, cyclosporin