Today we discussed a AKI, normal AG metabolic acidosis, and c/f Fanconi syndrome in the setting of NRTI-induced Fanconi syndrome.

  • Fanconi syndrome
    • Characterized by the following:
      • Hypophosphatemia (due to phosphaturia)
      • Renal glucosuria (glucosuria with a normal plasma glucose concentration)
        • NOTE: Remember that you typically do not induce significant glucosuria at serum glucose < 200 mg/dL. This patient had a serum glucose of 203 mg/dL and urine glucose of 500 mg/dL.
      • Moderate to severe hypokalemia
      • Proteinuria
      • Non-gap hyperchloremic metabolic acidosis
  • Etiologies of Fanconi syndrome can be separated into the following:
    • Congential/genetic conditions (i.e., disorders of tyrosine metabolism, galactosemia, fructose intolerance, Wilson disease, mitochondrial cytopathies)
    • Acquired causes (i.e., think medications, heavy metals, MGUS)
      • One of the main acquired causes of Fanconi syndrome includes the following medications and in our patient we discussed the possibility of tonofovir-inducing proximal RTA.
      • The short list:
        • Aminoglycosides
        • Cisplatin
        • Ifosfamide
        • Valproic acid
      • Though not on the list, tenofovir has been implicated in acquired Fanconi syndrome and the primary literature review reveals that there are case reports of this though it is not a widespread entity. See linke to article: Acquired Fanconi Syndrome with Tenofovir Therapy
    • Tenofovir and nephrotoxicity
      • There are no formal guidelines on monitoring renal impairment when taking tenofovir. Given the irreversible renal damage, it is suggested that patietns should be followed closely in the 1-1.5 years after initiating tenofovir with a urinalysis, serum creatinine, and potassium.
  • The importance of the urine anion gap [(Na + K) – Cl]
    • Measurement is helpful in evaluating patients with a normal anion gap (hyperchloremic) metabolic acidosis and estimates the urinary ammonium excretion
    • Positive indicates that Na + K > Cl à c/w distal RTA
      • Positive urine anion gap is c/w low or normal ammonium excretion and can be indicative of distal RTA which is a derangement in ammonium excretion
    • Negative indicates that Cl > Na + K à c/w proximal RTA
      • Ammonium is normal excreted with chloride and thus increased urinary ammonium excretion usually occurs with increased urine chloride
    • Note: The urine anion gap can be inaccurate when unmeasured anions (i.e., bicarbonate) are present
  • In addition, we touched on the renal tubular acidoses at large and the summary of clinical features is below:
Type 1 Type 2 Type 4
Primary defect Impaired ability to excrete H+ in DISTAL tubule Impaired HCO3 reabsorption in PROXIMAL tubule Decreased secretion or effect of aldosterone
Plasma bicarb < 10 12-20 > 17
Urine pH pH > 5.5 pH < 5.5 pH < 5.5
Urine anion gap Positive Negative Positive
Plasma potassium Low-normal Low-normal High
Nephrocalcinosis Common Rare Rare


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