14- RTA

• Renal Tubular Acidosis (RTA)


  A group of disorders in which metabolic acidosis results from defects in the ability of the renal tubules to maintain acid-base balance
• Types of RTA


  • Type I (Distal)
  • Type II (Proximal)
  • Type III (Combination of Type I and Type II, does not exist in practice)
  • Type IV (Hyperkalemic)
• RTA


  • All types are characterized by a normal anion gap (hyperchloremic) metabolic acidosis
• Type I (Distal) RTA


  Defects in distal hydrogen ion excretion (impaired acidification in the distal tubule)
• Type II (Proximal) RTA


  Reduced HCO3 reabsorption in the proximal tubule
• Type IV (Hyperkalemic) RTA

  Hypoaldosteronism (Reduced aldosterone secretion or responsiveness)
• Severity of RTA types


  • Type I: Severe
  • Type II: Mild
  • Type IV: Mild - moderate
• Plasma HCO3 levels in RTA types

  • Type I: <10 mEq/L
  • Type II: 12 - 20 mEq/L
  • Type IV: <17 mEq/L
• Urine pH in RTA types

  • Type I: >5.5
  • Type II: <5.5
  • Type IV: <5.5
• Potassium levels in RTA types


  • Type I: Low (few exceptions)
  • Type II: Low
  • Type IV: High
• Nephrolithiasis/nephrocalcinosis in RTA types


  • Type I: Yes (due to hypocitraturia, hypercalciuria, and alkaline urine)
  • Type II: No
  • Type IV: No
• Urine Ca++/creatinine ratio in RTA types


  • Type I: Increased
  • Type II: Normal
  • Type IV: Normal
• Urine anion gap in RTA types


  • Type I: Positive
  • Type II: Negative
  • Type IV: Negative
• Major Causes of RTA

  • Type I RTA
  • Type II RTA
  • Type IV RTA
• Type I RTA - Primary


  • Idiopathic
  • Familial
  • Autosomal recessive
  • Autosomal dominant
• Type II RTA - Primary


  • Idiopathic
  • Familial
  • Autosomal Recessive
  • Autosomal dominant
  • Cystinosis
  • Tyrosinemia
  • Fructose intolerance
  • Galactosemia
  • Glycogen storage disease (type I)
  • Wilson disease
  • Lowe syndrome
• Type IV RTA - Reduced Aldosterone Absorption


  • Hyporeninemic hypoaldosteronism
  • Diabetic nephropathy
  • Tubulointerstitial disease
  • Drugs e.g. NSAIDs
  • Angiotensin inhibitors e.g. ACEI, ARB, direct renin inhibitors
  • Chronic heparin therapy
  • Primary adrenal insufficiency
  • Inherited disorders
• Type IV RTA - Secondary

  • Autoimmune disorders
  • Sjögren's syndrome
  • Autoimmune hepatitis/primary biliary cirrhosis
  • SLE
  • Rheumatoid arthritis
  • Drugs e.g. Amphotericin B
  • Hypercalciuric conditions
  • Hyperparathyroidism
  • Vitamin D intoxication
  • Sarcoidosis
  • Idiopathic hypercalciuria
  • Wilson disease
• Type IV RTA - Aldosterone Resistance


  • Potassium-sparing diuretics (spironolactone, eplerenone, amiloride, and triamterene)
  • Antibiotics
  • Pseudo-hypoaldosteronism I
  • SLE
  • Sickle cell disease
• Type I RTA (distal)


  Low K, High URINE PH
• Type I RTA (distal)


  1. H+/K+ pump defect

  2. K+ lost in urineàhypokalemia

  3. H+ builds up in blood à acidosis in blood & alkaline urine (>5.5)
• Type I RTA (distal)


  • Urine is alkaline [PH > 5.5]
  • Calcium oxalate stones (recurrent)
  • Nephrocalcinosis of renal parenchyma
  • Stones & nephrocalcinosis can also be due to hypercalciuria & hypocitraturia
• Causes of Type I RTA (distal)


  • Amphotericin
  • Topiramate
  • SLE
  • Sjogren
  • Chronic hepatitis (cirrhosis)
  • Hypercalciuric conditions
• Treatment for Type I RTA (distal)


  PO bicarbonates + PO potassium (K+)
• Type II RTA (proximal)


  Low K, Low URINE PH
• Type II RTA (proximal)


  HCO3 channel defectàloss of bicarbonate
• Type II RTA (proximal)


  • May lead to rickets & osteomalacia
• Causes of Type II RTA (proximal)


  • Amyloidosis
  • Myeloma
  • Heavy metals
  • Acetazolamide
  • Fanconi syndrome
• Type II RTA (proximal)


  • Multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting
  • May be hereditary or acquired
  • In children: failure to thrive, growth retardation, rickets
  • In adults: osteomalacia and muscle weakness
• Diagnosis of Type II RTA (proximal) is by showing glucosuria, phosphaturia, and aminoaciduria
• Treatment for Type II RTA (proximal)


  Bicarbonate and potassium replacement, removal of offending nephrotoxins, and treating renal failure
• Type IV RTA (hypo-renin + hypo-aldosterone)


  High K, Low Na, Low URINE PH
• Type IV RTA (hypo-renin + hypo-aldosterone)


  • Low amount of aldosterone or resistance to aldosterone
  • High urine sodium despite sodium free diet
• Causes of Type IV RTA (hypo-renin + hypo-aldosterone)


  • Addison's disease
  • Diabetic nephropathy
• Treatment of Type IV RTA (hypo-renin + hypo-aldosterone): Fludrocortisone