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Definition

• Group of disorders that cause a metabolic acidosis due to defects in the renal tubules
  • Net retention of HCl
  • Net loss of NaHCO₃

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Pathophysiology

The kidney regulates acid-base balance two main ways:

• Reabsorption of filtered HCO₃
  • >80% of the bicarbonate filtered by the glomerulus is reabsorbed in the proximal renal tubules via Na-H exchange

• Acid excretion
  • Collecting ducts of the nephron excrete hydrogen ions buffered by NH₃ and PO₃ (so the pH of the urine doesn’t destroy the nephron)
    • Extra production of NH₃ is stimulated by intracellular acidosis.

• 3 step process
  • Reabsorption of sodium to create a negative gradient in the tubular lumen
  • Excretion of hydrogen by H-K-ATPase and reabsorption of potassium
  • Prevention of hydrogen ions from diffusing back out of the tubular lumen

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Initial Presentation

• Patients diagnosed with an RTA must first be diagnosed with a metabolic acidosis
  • Decreased pH with decreased HCO₃
• After this is determined, the anion gap must be calculated and found to be normal
  • AG = Na – (Cl + HCO₃) = 8-12

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Differential for NAGMA

• Ureteric diversion
• Small bowel fistulae
• Excessive saline
• Diarrhea
• Carbonic anhydrase inhibitors
• Renal tubular acidosis
• Adrenal insufficiency
• Pancreatic fistulae

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Type I (distal) RTA

• Cause
  • Defect in the distal hydrogen ion excretion
• Pathophysiology
  • Failure of the H-ATPase proton pump (most common cause)
    • Inability to acidify urine < 5.5
    • Hypokalemia
  • Increased hydrogen ion permeability of the luminal membrane

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Type II (proximal) RTA

• Cause
  • Defect in proximal bicarbonate reabsorption
• Pathophysiology
  • Damage to the proximal tubule that leads to progressive bicarbonate wasting in the urine

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Type IV (hypoaldosteronism)

• Cause
  • Reductions in aldosterone secretion and responsiveness
• Pathophysiology
  • Decreased rate of proton secretion rather than an intrinsic defect in the tubule’s capacity to generate normal pH gradient
  • Hyperkalemia causes reduced urine NH4, which in turns leads to more acidic urine
    • Hydrogen ions have nothing to bind to

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Diagnostic Work-Up

• RTAs should be considered in any patient with a normal anion gap metabolic acidosis
  • Need ABG and BMP
• Once this determination is made:
  • Urine pH
    • > 5.5 in type I (distal)
    • < 5.5 in type II (proximal) and type IV
  • Urine ammonium
    • Elevated in type II (proximal)
    • Decreased in type I (distal) and type IV
    • Most labs can’t measure urine ammonium directly:
      • Urine Anion Gap (urine Na+K+Cl)
        • (+) UAG = > 20
          • Type I (distal) and type IV
        • (-) UAG = < – 20
          • Type II (proximal)
  • Serum potassium
    • Elevated in type IV
    • Decreased in type I and II

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Treatment

• Type I (distal)
  • Urinarary Alkali Therapy
    • Sodium bicarbonate
      • Increased risk of nephrolithiasis due to bicarbonaturia
        • Use potassium citrate instead
• Type II (proximal)
  • Much more difficult to treat due to the INCREASED bicarbonate diuresis during bicarbonate therapy
  • Alkali therapy (10x the dose for type I) AND potassium salt repletion as bicarbonaturia INCREASES urinary potassium losses
  • Thiazide diuretics if large alkali doses ineffective or not tolerated
    • Diuresis reduces urinary bicarbonate loss by increasing proximal sodium reabsorption
      • Which secondarily increased bicarbonate reabsorption
• Type IV
  • Stop any medication causes or treat underlying condition (hypoaldosteronism)
    • Mineralcorticoid (fludrocortisone) and glucocorticoid (hydrocortisone)
  • Potassium repletion

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References

1. Rodríguez Soriano J. Renal tubular acidosis: the clinical entity. Journal of the American Society of Nephrology : JASN. 2002; 13(8):2160-70. [pubmed]
2. Skelton LA, Boron WF, Zhou Y. Acid-base transport by the renal proximal tubule. Journal of nephrology. ; 23 Suppl 16:S4-18. [pubmed]
3. Hamm LL, Nakhoul N, Hering-Smith KS. Acid-Base Homeostasis. Clinical journal of the American Society of Nephrology : CJASN. 2015; 10(12):2232-42. [pubmed]
4. The Curbsiders.  Episode 104. https://thecurbsiders.com/internal-medicine-podcast/104-renal-tubular-acidosis-kidney-boy-joel-topf-md
5. DB’s Medical Rants.  http://www.medrants.com/archives/8897
6. Oh M, Carroll HJ. Value and determinants of urine anion gap. Nephron. 2002; 90(3):252-5. [pubmed]
7. Rodríguez Soriano J. Renal tubular acidosis: the clinical entity. Journal of the American Society of Nephrology : JASN. 2002; 13(8):2160-70. [pubmed]
8. Karet FE. Mechanisms in hyperkalemic renal tubular acidosis. Journal of the American Society of Nephrology : JASN. 2009; 20(2):251-4. [pubmed]