Renal Tubular Acidosis (RTA)

BASICS

Definition: Group of disorders characterized by an inability of the kidney to resorb bicarbonate (HCO₃⁻) or secrete hydrogen ions, resulting in normal anion gap metabolic acidosis with normal or near-normal renal function.
Types:
Type I (distal): Impaired distal H⁺ secretion; urine pH >5.5.
Type II (proximal): Defective proximal HCO₃⁻ reabsorption; urine pH <5.5.
Type III: Extremely rare, autosomal recessive, with osteopetrosis, cerebral calcification, intellectual disability.
Type IV (hypoaldosteronism): Aldosterone deficiency/resistance; hyperkalemia; urine pH <5.5.

Type II (proximal) RTA: Male > female (with isolated HCO₃⁻ reabsorption defect).

Type I RTA:
Causes: Autoimmune (Sjögren, RA, SLE), drugs (amphotericin B, lithium), genetic, toxins, obstructive uropathy.
Incomplete and voltage-dependent variants exist.
Type II RTA:
Causes: Genetic, Fanconi syndrome, drugs (carbonic anhydrase inhibitors, chemotherapy, antiretrovirals, aminoglycosides), dysproteinemias, metabolic diseases.
Type IV RTA:
Causes: Drugs (NSAIDs, ACEi, ARBs, heparin, cyclosporine), diabetic nephropathy, adrenal insufficiency, pseudohypoaldosteronism, tubulointerstitial disease.

Type I: AE1 chloride-bicarbonate exchanger mutations (autosomal dominant/recessive, may have hemolytic anemia).
Type II: NBCe1 transporter mutations (autosomal recessive; growth retardation, ophthalmologic, intellectual disability).
Type IV: Some familial cases (PHA type I).

Often asymptomatic (esp. type IV)
Children: Failure to thrive, rickets
Anorexia, nausea, vomiting, constipation, weakness, polyuria/polydipsia (hypokalemia, hypercalciuria), osteomalacia

Serum: Hyperchloremic metabolic acidosis, normal anion gap.
Type I, II: Hypokalemia
Type IV: Hyperkalemia
Urine pH:
Type I: >5.5 in acidosis
Type II: <5.5 (unless HCO₃⁻ >12–18 mEq/L)
Type IV: <5.5
Urine anion gap: Positive in types I & IV (impaired NH₄⁺ excretion).
Type II: Look for Fanconi syndrome features (glycosuria, phosphaturia, aminoaciduria).
BUN/Cr: Should be normal.
Type I (children): Audiogram, MRI/CT for hearing loss.
Type II: Gold standard—HCO₃ loading test; FeHCO₃ >15% diagnostic.
Type IV: Exclude drugs, check for hypoaldosteronism.

Type I: 1–2 mEq/kg/d (adults), 3–4 mEq/kg/d (children) of HCO₃⁻, divided 3–4 times daily. May need K⁺ supplementation.
Type II: 10–15 mEq/kg/d, divided 4–6 times daily. Often need K⁺, PO₄, vitamin D supplementation.
Type IV: Stop offending drugs, treat hypoaldosteronism, restrict dietary K⁺, consider loop/thiazide diuretics, polystyrene sulfonate, fludrocortisone if needed. May need 1–5 mEq/kg/d alkali.

Type I/II: Thiazide diuretics may help reduce alkali requirement but increase risk of hypokalemia.
Type I: Indomethacin may help with polyuria/hypokalemia.
Type IV: Fludrocortisone (esp. in diabetes/amyloidosis).

Severe acidosis, unreliable patient, persistent emesis, infants with severe FTT.

Monitor electrolytes 1–2 weeks after starting therapy, then monthly until stable.
Long-term: poor compliance common due to frequent dosing.

Consider RTA in normal anion gap metabolic acidosis with normal renal function.
Type I: Urine pH >5.5 in acidemia, positive UAG.
Type II: Urine pH <5.5 unless HCO₃⁻ >12–18 mEq/L.
Type IV: Most common, hyperkalemia, mild acidemia.
Treatment is oral alkali, potassium supplementation or restriction as needed, and address underlying causes.