Renal Tubular Acidosis

Definition

• Metabolic acidosis caused by renal tubular dysfunction.. inability to excrete acid.

• 
• Different Types
  • Type II aka PROXIMAL
    • A type of Fanconi syndrome (which is any type of proximal tubular dysfunction, different Fanconi syndromes exist that prevent reabsorption of different types of metabolites (AA, glucose, bicarb, etc.)
    • Inability to reabsorb HCO3- in the proximal tubule.
    • HINT: Also inability to absorb other electrolytes (Potassium [hypokalemia], phosphate [hypoPh], glucose [glycosuria]). 
  • Type I (most common) aka DISTAL
    • Inability to excrete H+ in distal tubule
    • If urine pH is HIGH or NORMAL = distal tubule not working to acidify the urine to get rid of extra acid in an acidotic state. = Type 1 RTA
    • Causes:
      • Cirrhosis
      • Autoimmune (SLE, Sjogrens)
      • Hephrocalcinosis
      • Drugs (Lithium, Amphotericin)
      • Others: Hereditary, Sickle Cell
  • Type IV (Aldosterone Dependent)
    • Hypoaldosteronism (primary, hyporeninemic)
    • Drugs (Spironolactone, Amiloride, NSAIDs, ACEi, Heparin)
    • Pseudohypoaldosteronism  
  • Type III
    • Extremely RARE form of childhood acidosis.
    • This is mixed Type I and Type II due to carbonic anhydrase deficiency.
    • Children get mental retardation, cerebral calcinosis, and non-vitamin D rickets.
    • This type is generally ignored because it is so rare. 
• Presentation:
  • Present "sick"
    • Headache, Nausea/vomiting, Weakness
    • Kussmaul Breathing
    • Hypokalemia (Type I and Type II)
    • Renal Stones (Type I)
    • Bone Demineralization (more Type II)
• Differentiate:
  • Quick Summary:

  • Type	Features	Treatment
    Type I (dRTA)	Low K+ Urine pH > 5.3	Potassium Citrate (+fluids)
    Type II (pRTA)	Low K+ Urine pH = 5.3 (normal), later < 5.3 Glycosuria, proteinuria, phosphaturia	Potassium Citrate (+fluids)
    Type IV	High K+ Urine pH < 5.3	Fludrocortisone Loop Diuretics

  • 	Type II (pRTA)	Type I (dRTA)	Type IV
    Mechanism	HCO3- reabsorption defect	H+ secretion defect in Distal Tubules   - Intercalated cell  dysfunction (unable to  reabsorb K+ and secrete H+)	Hypoaldosteronism
    Causes	Fanconi's Syndrome (FS is any proximal tubule dysfunction, pRTA is a type of Fanconi Syndrome)   Multiple Myeloma, Amyloidosis   Drugs (Acetazolamide, Tenofovir)   Scleroderma (antibody to H+                        ATPase) Heavy Metal Poisoning Vitamin D Def. Hereditary	Autoimmune (SLE, Sjogrens) Cirrhosis Nephrocalcinosis Hypercalciuria Drugs (Lithium, Amphotericin) Others (Hereditary, Sickle Cell)	Hypoaldosteronism  - Primary  - Hyporeninemic  - DIABETES!!!!! Drugs  - Spironolactone  - Amiloride  - Heparin  - ACEi, NSAIDs (hypo-aldo activity) Pseudohypoaldosteronism
    Important Associations	Bone Demineralization (Poor phosphate absorption)	Renal Stones  (Hypocitraturia)
    Labs	Bicarb: 12-20 (less severe than dRTA) Low K+ (glycosuria, low molecular weight proteinuria, phosphate wasting)   Urine pH = 5.3 (normal) or LOW    Can rise high if high HCO3- load  [Later Urine pH < 5.3]  [Urine variable bc still able to secrete H+ and reabsorb HCO3- in distal tubule] Urine Anion Gap - Variable Urine Chloride HIGH > 100	Bicarb < 10 (SEVERE!) Low K+ UrinepH > 5.3 Urine Anion Gap POSITIVE   Should be LOW due to extra    NH4+ in acidified urine. Urine Chloride HIGH >100	High K+ Urine pH < 5.3 Urine Anion Gap - POSITIVE Urine Chloride HIGH >100
    Treatment	Potassium Citrate	Sodium Bicarb     (GI discomfort,  Bad taste) Potassium Citrate	Fludrocortisone (often not enough mineralcorticoids) Loop Diuretics

    
     
• ALL THESE STATES WILL HAVE HIGH URINE CHLORIDE!!! Often >100 MMOL/L
  
   
• Bottom Line: If you see non-anion gap metabolic acidosis (hyperchloremic) in a non-diarrhea patient, think RTA
  • Calculate UAG to determine etiology (RTA vs. Diarrhea)
• Bottom Line: Look at serum bicarb and urine pH: very low HCO3 and high pH, think of Type I RTA
• Bottom Line: Correct underlying cause

Problems Created by RTA

• Metabolic Acidosis
  • Nausea, headache
• Hypercalciuria

1. H+ directly inhibits reabsorption of Ca++
2. Bone resorption (acts as buffer), osteoclasts activated (RANKL-mediated), release Ca, Na, K+, CO3-, PO4 from bone, which buffer plasma towards physiological pH.

• Hypocitraturia (Type 1)
  • Occurs in all metabolic acidosis, but most profound in dRTA.
    • Hypocitraturia can also occur in:
      • Potassium depletion (cellular acidosis)
      • Bacteuria (bacteria metabolize citrate)
      • Acidifying conditions (chronic diarrhea, renal insufficiency)
  • Causes calcium stone formation
    • --> obstructive uropathy.
  • Causes nephrocalcinosis (interstitial calcification)
    • --> causes inflammation and interstitial fibrosis.
• Hypokalemia (Type 1 and Type 2)
  • GI and/or renal K+ losses.
  • Occurs in most forms of chronic metabolic acidosis
    • Acutely K+ can equalize by H+/K+ transporter (shifts K+ out of cells)
    • Chronically leads to K+ depletion. (H+ ATPase pump fails, causing Na+/K+ Exchager to be dominant force maintaining electroneutrality, causing K+ excretion)

Treatment