Type 4 Renal Tubular Acidosis (RTA)

Etiology

Hypoaldosteronism (see Hypoaldosteronism, [[Hypoaldosteronism]])

Decreased Aldosterone Synthesis

  • Inherited Disorders
    • 21 Hydroxylase Deficiency
    • Pseudohypoaldosteronism Type 2 (Gordon’s Syndrome)
  • Hyporeninemic Hypoaldosteronism
  • Drugs
    • Angiotensin Converting Enzyme (ACE) Inhibitors
      • Captopril (Capoten) (see Captopril, [[Captopril]])
      • Enalapril (Vasotec, Enalaprilat) (see Enalapril, [[Enalapril]])
      • Fosinopril (Monopril) (see Fosinopril, [[Fosinopril]])
      • Lisinopril (Zestril) (see Lisinopril, [[Lisinopril]])
      • Moexipril (Univasc) (see Moexipril, [[Moexipril]])
      • Perindopril (Coversyl, Coversum, Preterax, Aceon) (see Perindopril, [[Perindopril]])
      • Quinapril (Accupril) (see Quinapril, [[Quinapril]])
      • Ramipril (Altace) (see Ramipril, [[Ramipril]])
      • Trandolapril (Mavik) (see Trandolapril, [[Trandolapril]])
    • Angiogensin II Receptor Blockers (ARB’s)
      • Candesartan (Atacand) (see Candesartan, [[Candesartan]])
      • Fimasartan (Kanarb) (see Fimasartan, [[Fimasartan]])
      • Irbesartan (Avapro, Aprovel, Karvea) (see Irbesartan, [[Irbesartan]])
      • Losartan (Cozaar) (see Losartan, [[Losartan]])
      • Olmesartan (Benicar, Olmecip) (see Olmesartan, [[Olmesartan]])
      • Telmisartan (Micardis) (see Telmisartan, [[Telmisartan]])
      • Valsartan (Diovan) (see Valsartan, [[Valsartan]])
    • Heparins
      • Enoxaparin (Lovenox) (see Enoxaparin, [[Enoxaparin]])
      • Heparin (see Heparin, [[Heparin]])
    • Renin Inhibitors
      • Aliskiren (Tekturna, Rasilez) (see Aliskiren, [[Aliskiren]]): renin inhibitor (may cause hyperkalemia when used in combination with ACE inhibitors or ARB’s)
  • Other

Aldosterone Resistance

  • Inherited Disorders
    • Pseudohypoaldosteronism Type 1
  • Drugs
    • Aldosterone Antagonists
      • Drospirenone (Yasmin, Yasminelle, Yaz, Beyaz, Ocella, Zarah, Angeliq) (see Drospirenone, [[Drospirenone]])
      • Eplerenone (Inspra) (see Eplerenone, [[Eplerenone]])
      • Spironolactone (Aldactone) (see Spironolactone, [[Spironolactone]])
    • Epithelial Sodium Channel (ENaC) Antagonists
  • Other

Physiology

  • Aldosterone Deficiency/Resistance -> Impaired Distal Tubular Ammonium Generation: results in impaired hydrogen ion excretion (impaired renal acid excretion)
    • Renal Bicarbonate Loss Results in Bicarbonate Being Replaced by Chloride, Resulting in Hyperchloremia

Diagnosis

  • Serum Potassium: normokalemia/hyperkalemia
  • Urine pH: <5.4
  • Urine Anion Gap: (urine Na+ + urine K+) – (urine Cl-)
    • Normal: -20 to -50 mEq/L
    • Positive: due to decreased renal ammonium ion (NH4+) excretion, as NH4Cl

Clinical Manifestations

Renal Manifestations


Treatment

  • Bumetanide (Bumex) (see Bumetanide, [[Bumetanide]])
  • Sodium Bicarbonate (see Sodium Bicarbonate, [[Sodium Bicarbonate]]): may be added to bumex therapy
  • Alternate Therapy: Fludrocortisone (Florinef) (see Fludrocortisone, [[Fludrocortisone]])
    • Dose: 0.2-0.5 mg/day

References

  • xx