Fluoride induced nephrotoxicity

Fluoride induced nephrotoxicity is kidney injury due to toxic levels of serum fluoride, commonly due to metabolism of fluoride-containing drugs, such as methoxyflurane, releasing inorganic fluoride inside the body.[1][2][3]

The kidney injury is characterised by failure to concentrate urine, leading to polyuria, and subsequent dehydration with hypernatremia and hyperosmolarity. Inorganic fluoride inhibits adenylate cyclase activity required for antidiuretic hormone effect on the distal convoluted tubule of the kidney. Fluoride also stimulates intrarenal vasodilation, leading to increased medullary blood flow, which interferes with the counter current mechanism in the kidney required for concentration of urine.

Fluoride induced nephrotoxicity is dose dependent, typically requiring serum fluoride levels exceeding 50 micromoles per liter to cause clinically significant renal dysfunction,[4] which is likely when the dose of methoxyfluorane exceeds 2.5 MAC hours.[5][6] (Note: "MAC hour" is the multiple of the minimum alveolar concentration (MAC) of the anesthetic used times the number of hours the drug is administered, a measure of the dosage of inhaled anesthetics.)

Elimination of fluoride depends on glomerular filtration rate. Thus, patients with renal insufficiency will maintain serum fluoride for longer period of time, leading to increased risk of fluoride induced nephrotoxicity.


  1. Cousins MJ, Skowronski G, Plummer JL. Anaesthesia and the kidney. Anaesth Intensive Care. 1983 Nov;11(4):292-320.
  2. Baden JM, Rice SA, Mazze RI. Deuterated methoxyflurane anesthesia and renal function in Fischer 344 rats. Anesthesiology. 1982 Mar;56(3):203-6.
  3. Mazze RI. Methoxyflurane nephropathy. Environ Health Perspect. 1976 Jun;15:111-9.
  4. Cousins MJ, Greenstein LR, Hitt BA, Mazze RI. Metabolism and renal effect of enflurane in men. Anesthesiology 1976; 44:44-53.
  5. VanDyke R. Biotransformation of volatile anesthetics with special emphasis on the role of metabolism in the toxicity of anesthetics. Can Anaesth Soc J 1973;20:21-33.
  6. White AE, Stevens WC, Eger EI II, Mazze RI, Hitt BA. Enflurane and methoxyflurane metabolism at anesthetic and subanesthetic concentrations. Anesth Analg 1979;58:221-4/
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