Type 1 or distal RTA Type 2 or proximal RTA Type 4 or hyperkalemic RTA
Etiology Single gene defects: Isolated Hypoaldosteronism
● A.R: ATPV0A4 and ATPV1B1 → ● SLC4A4 → NBCe1 (Na/HCO3 ● Addison's
H/ATPase symporter) ● Renal failure or hyporeninism
○ deafness ○ AD ○ A. glomerulonephritis
● A.D. or A.R:SLC4A1 → AE1 ○ AR (ocular abnormalities) ○ Diabetic nephropathy
(Cl/HCO3 channel) ● Sporadic (transient) ○ SLE nephropathy
Autoimmune diseases Fanconi Syndrome ○ AIDS
● SLE ● Inherited ○ NSAIDs, ACE-I, heparin
● Sjögren ○ Cystinosis (#1) ● Gordon Syndrome: Gain of
Drugs ○ Galactosemia function in NCCT → Na
● Amphotericin B ○ Wilson's retention → ↓ RAAS
● Lithium ● Drugs: expired tetracyclines, Aldosterone resistance
● Foscarnet aminoglycosides, ifosfamide, ● Distal diuretics
Systemic diseases cisplatin, acetazolamide ● Pseudohypoaldosteronism I:
● ↑PTH ● Multiple myeloma mineralocorticoid R (A.D.) or
● Sarcoidosis ● Heavy metal poisoning (mercury) ENac mutation (A.R.)
Pathophysiology Failure to secrete H from type A Defect in PCT bicarbonate reabsorption → Aldosterone deficiency or resistance →
intercalated cells → metabolic acidosis HCO3 loss in urine ↓Na, ↑H & ↑K
Clinical features ● Nephrocalcinosis & litiasis ● NO stones or nephrocalcinosis ● NO stones or nephrocalcinosis
● Polyuria ● Rickets or osteomalacia ● Polyuria
● Bone demineralization ● Stunted growth ● Bone demineralization
● Impaired growth and FTT ● Polyuria ● Stunted growth
● ↓K: muscle weakness, hyporeflexia, ● ↓K symptoms (mostly in Fanconi) ● ↑K: muscle weakness, peaked T
ECG abnormalities waves)
Electrolyte levels ● Hypokalemia → improves w/ ● Hypokalemia → worsens w/ ● Hyperkalemia
alkaline therapy alkaline therapy ● Hyponatremia
● Hypocalcemia & hypercalciuria ● Hyperchloremia & normal anion ○ Normal in Gordon
● Hyperchloremia & normal anion gap ● Hyperchloremia & normal anion
gap ● Fanconi: ↓PO4, ↓uricemia gap
Diagnosis ● Urine pH > 5.5 & doesn't fall below ● Urine pH < 5.5 but rapidly rises > ● Urine pH < 5.5
5.3 after acid load test 7.5 after HCO3 load ● Positive urine anion gap due to
● Low NH4 & citrate excretion ● Fanconi Sd: aminoaciduria, persistent Na wasting
glucosuria, phosphaturia ● Normal or hypocalciuria
Etiology Single gene defects: Isolated Hypoaldosteronism
● A.R: ATPV0A4 and ATPV1B1 → ● SLC4A4 → NBCe1 (Na/HCO3 ● Addison's
H/ATPase symporter) ● Renal failure or hyporeninism
○ deafness ○ AD ○ A. glomerulonephritis
● A.D. or A.R:SLC4A1 → AE1 ○ AR (ocular abnormalities) ○ Diabetic nephropathy
(Cl/HCO3 channel) ● Sporadic (transient) ○ SLE nephropathy
Autoimmune diseases Fanconi Syndrome ○ AIDS
● SLE ● Inherited ○ NSAIDs, ACE-I, heparin
● Sjögren ○ Cystinosis (#1) ● Gordon Syndrome: Gain of
Drugs ○ Galactosemia function in NCCT → Na
● Amphotericin B ○ Wilson's retention → ↓ RAAS
● Lithium ● Drugs: expired tetracyclines, Aldosterone resistance
● Foscarnet aminoglycosides, ifosfamide, ● Distal diuretics
Systemic diseases cisplatin, acetazolamide ● Pseudohypoaldosteronism I:
● ↑PTH ● Multiple myeloma mineralocorticoid R (A.D.) or
● Sarcoidosis ● Heavy metal poisoning (mercury) ENac mutation (A.R.)
Pathophysiology Failure to secrete H from type A Defect in PCT bicarbonate reabsorption → Aldosterone deficiency or resistance →
intercalated cells → metabolic acidosis HCO3 loss in urine ↓Na, ↑H & ↑K
Clinical features ● Nephrocalcinosis & litiasis ● NO stones or nephrocalcinosis ● NO stones or nephrocalcinosis
● Polyuria ● Rickets or osteomalacia ● Polyuria
● Bone demineralization ● Stunted growth ● Bone demineralization
● Impaired growth and FTT ● Polyuria ● Stunted growth
● ↓K: muscle weakness, hyporeflexia, ● ↓K symptoms (mostly in Fanconi) ● ↑K: muscle weakness, peaked T
ECG abnormalities waves)
Electrolyte levels ● Hypokalemia → improves w/ ● Hypokalemia → worsens w/ ● Hyperkalemia
alkaline therapy alkaline therapy ● Hyponatremia
● Hypocalcemia & hypercalciuria ● Hyperchloremia & normal anion ○ Normal in Gordon
● Hyperchloremia & normal anion gap ● Hyperchloremia & normal anion
gap ● Fanconi: ↓PO4, ↓uricemia gap
Diagnosis ● Urine pH > 5.5 & doesn't fall below ● Urine pH < 5.5 but rapidly rises > ● Urine pH < 5.5
5.3 after acid load test 7.5 after HCO3 load ● Positive urine anion gap due to
● Low NH4 & citrate excretion ● Fanconi Sd: aminoaciduria, persistent Na wasting
glucosuria, phosphaturia ● Normal or hypocalciuria
