renal tubular acidosis (RTA) type II (proximal RTA)

Etiology

• genetic forms
  • carbonic anhydrase-2 deficiency
• associated conditions:
  • amyloidosis
  • multiple myeloma
  • autoimmune disorders including:
    • Sjogren's syndrome
    • systemic lupus erythematosus
  • chronic active hepatitis
  • interstitial nephritis
  • renal transplantation
  • cystinosis
  • Wilson's disease
  • Fanconi syndrome with aminoaciduria, glucosuria, phosphaturia hypophosphatemia, hypouricemia may result in RTA II
  • vitamin D deficiency
  • renal tubular proteinuria
• pharmacologic agents associated with isolated RTA-2
  • carbonic anhydrase inhibitors (acetazolamide)
  • sulfanilamide
  • topiramate
  • ifosfamide
  • tenofovir, cidofovir
  • tacrolimus
  • cyclosporine
  • tetracycline (outdated)
  • cisplatin (Fanconi syndrome)
• heavy metal toxicity
  • cadmium, copper, lead, mercury
• other toxins
  • toluene

Epidemiology

autosomal recessive form rare

Pathology

• defect in proximal tubule resorption of HCO3-

Genetics

• autosomal recessive form caused by mutation in SLC4A4 gene associated with severe renal tubular acidosis
• autosomal dominant form
• X-linked form ?

Clinical manifestations

• osteopenia (not as severe as type I)
• no nephrolithiasis
• growth retardation, short stature
• mental retardation
• bilateral glaucoma
• cataracts
• band-keratopathy

Laboratory

• metabolic acidosis
  • urine pH: generally < 5.5 as serum HCO3- declines, but may be > 5.5
  • serum HCO3-: 14-20 meq/L, ~16-18 meq/L
  • anion gap is normal
  • normal or negative urinary anion gap
• serum aldosterone normal to high
• hypokalemia (may be normal)
• aminoaciduria, glycosuria despite normal glucose, phosphaturia, hypophosphatemia (Fanconi syndrome)
• normal 24 hour urine citrate

Management

• attempt to treat the underlying cause
• HCO3- or citrate: 5-15 meq/kg/day may be required
  • citrate may cause fewer side effects than HCO3-
  • HCO3- wasting occurs with HCO3- therapy
  • HCO3- may not correct acidosis
• K+ replacement (HCO3- administration may cause hypokalemia)
  • a potassium-sparing diuretic may reduce renal potassium wasting
• thiazide diuretics
  • may increase proximal tubule resorption
  • inhibits Ca+2 excretion into the urine
  • may induce hypovolemia reducing GFR decreasing glomerular filtration of HCO3-

More general terms

• renal tubular acidosis (RTA)

Database

• OMIM: https://mirror.omim.org/entry/604278