FLUORIDE AND RENAL TOXICITY - A NEPHROLOG ISTS VIEWPOINT

Fluoride released from methoxyflurane (MOF) during its hepatic and ext rahepatic metabolism has been regarded as the major culprit responsibl e for MOF-induced nephrotoxicity. In the isolated, perfused rat kidney model, admixture of 1500 mu mol/1 fluoride to the perfusate resulted in tubular and glomerular damage with concomitant anuria. Fluoride adm inistration in Fischer 344 rats in vivo elicited a renal diabetes insi pidus-like syndrome that had also been observed in patients after MOF anaesthesia. The renal concentrating defect is most probably due to bo th dissipation of the corticomedullary osmolality gradient in the inte rstitium and failure of water reabsorption due to ADH refractoriness o f the distal tubular cells. Hypothetically, the underlying mechanism m ay be a fluoride-induced inhibition of enzymes involved in intracellul ar energy production such as ATPase or enolase. The degree of nephroto xicity correlates loosely with maximal serum fluoride levels, but can probably be modulated by further factors like intrarenal in situ forma tion 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 mu mol threshold, as predictors of cl inically relevant nephrotoxicity. To date, no nephrotoxic effects of s evoflurane could be demonstrated.