The American journal of pathology
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Clinical Trial
Spectrum and subcellular determinants of fluorinated anesthetic-mediated proximal tubular injury.
Currently used fluorinated anesthetics are chemically related to methoxyflurane (MF), a drug that caused many cases of clinical acute renal failure during previous widespread use. To determine whether newer fluorinated anesthetics might also have nephrotoxic effects, three currently used agents (isoflurane (IF), sevoflurane (SF), and desflurane) or MF were added to rat proximal tubular segments, followed by assessments of cell integrity (ATP levels and percent lactic dehydrogenase release). Ether served as a negative control. ⋯ Conversely, NAG levels remained stable in both control groups. The conclusions are that 1) currently used fluorinated anesthetics, particularly IF, share (but to a lesser degree) MFs tubulotoxic effects, 2) ATP depletion (probably due to decreased production) and Na,K-ATPase inhibition are likely contributing mechanisms, 3) fluoride is a prime determinant of this toxicity, and 4) tubular injury can be expressed at or near clinically relevant anesthetic/inorganic fluoride levels. That increased enzymuria can develop in patients after IF anesthesia suggests that the above in vitro data could have potential clinical relevance in selected patients.