Renal Tubular Acidosis

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    Definition

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

     

    • RTA.png
    • 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

     

    Urine Anion Gap

    • Kidney's ability excrete acid is characterized by urine NH4 (ammionium).  We don't have a test for ammonium in urine so we use urine anion gap.
    • If urine pH > 6.5  --> bicarb becomes predominant 
    • Should be calculated to determine etiology of hyperchloremic metabolic acidosis.
    • Urine Anion Gap (UAG = (Una + Uk) - Ucl
      • POSITIVE UAG = low NH4  (i.e. RTA)
      • NEGATIVE UAG = high NH4 (i.e. acid normally excreted - i.e. diarrhea).
    • Diarrhea (lose bicarb in gut) --> kidneys are working well (no RTA) --> will have negative UAG.
    • If RTA --> positive UAG (if pH < 6.5).

     

     

     

    Urine Osmolar Gap

    • If low, then lack of NH4 --> consistent with RTA

     

    • Both UAG and UOG help you diagnose RTA, but doesn't tell you the type
      • Fractional Excretion of phosphate (FEPhos) = 100x (urine Phos / Serum Phos) / (Urine Cr / Serum Cr)
      • Normal = 5-12% excreted
      • Fanconi's > 15% excreted

    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

    Distal RTA

    • Need to provide HCO3- to correct acidosis (lose HCO3 from continuous buffering of extra H+)
      • Need to tirate HCO3 to daily citrate excretion of (>300 mg/day)
    • Potassium Citrate
      • Delivers alkali to help with acidosis, corrects hypocitraturia
      • Prevents nephrocalcinosis and calcium stones.
      • Halts renal failure.
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