[Nephrotoxicity and fluoride from the viewpoint of the nephrologist].
Fluoride released from methoxyflurane (MOF) during its hepatic and extrahepatic metabolism has been regarded as the major culprit responsible for MOF-induced nephrotoxicity. In the isolated, perfused rat kidney model, admixture of 1500 mumol/l fluoride to the perfusate resulted in tubular and glomerular damage with concomitant anuria. Fluoride administration in Fischer 344 rats in vivo elicited a renal diabetes insipidus-like syndrome that had also been observed in patients after MOF anaesthesia. The renal concentrating defect is most probably due to both dissipation of the corticomedullary osmolality gradient in the interstitium and failure of water reabsorption due to ADH refractoriness of the distal tubular cells. Hypothetically, the underlying mechanism may be a fluoride-induced inhibition of enzymes involved in intracellular energy production such as ATPase or enolase. The degree of nephrotoxicity correlates loosely with maximal serum fluoride levels, but can probably be modulated by further factors like intrarenal in situ formation of fluoride, urinary pH and flow, and especially, the presence of other nephrotoxins. This mitigates the importance of maximal fluoride serum levels, especially the 50 mumol threshold, as predictors of clinically relevant nephrotoxicity. To date, no nephrotoxic effects of sevoflurane could be demonstrated.
Bosch
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Medizinische Klinik I, Klinikum Grosshadern, Ludwig-Maximilians-Universität München.
D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D005459:Fluorides / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008657:Metabolic Clearance Rate / Q000502:physiology; D008733:Methoxyflurane / Q000493:pharmacokinetics / Q000633:toxicity; D008738:Methyl Ethers; D051381:Rats; D011916:Rats, Inbred F344; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D008733:Methoxyflurane; D000077149:Sevoflurane; D005459:Fluorides
Nephrotoxizität und Fluorid aus der Sicht des Nephrologen.