Effect of inorganic fluoride on the renal concentrating mechanism. Possible nephrotoxicity in man.

Abstract

Abstract It has been proposed that the renal defect in water conservation occurring after administration of methoxyflurane anesthesia may be due to a nephrotoxic effect of inorganic fluoride released during metabolic degradation of the anesthetic. To investigate this possibility, the effects of inorganic fluoride (NaF) on CH 2 O, TcH 2 O, Umax and corticomedullary sodium gradient were studied in the dog. During steady state 10 per cent mannitol diuresis, intravenous infusion of NaF at 4 to 5 mg. per minute resulted in a 20 to 40 per cent increase in V and a 25 to 74 per cent reduction in TcH 2 O, while GFR (glomerular filtration rate) and UNaV remained stable. Infusion of NaF during hydropenia reduced Umax from 1,473 ± 97.9 mOsm. per liter to levels approaching Posm. This fall in Uosm was accompanied by a significant reduction in mean papillary sodium concentration from 222 to 127 mEq of sodium per kilogram of tissue H 2 O, but not by natriuresis. TcH 2 O was markedly reduced by NaF during hypertonic (2 per cent) NaCl diuresis. Fluoride was consistently without effect on CH 2 O or the ratio, CH2OV, during hypotonic (0.45 per cent) NaCl diuresis. Blood fluoride levels of 204 to 426 μM per liter were attained in these studies. Feeding of 600 mg. of NaF per day for periods of 2 to 5 weeks produced only relatively mild hyperfluoremia (15 to 31 μM per liter) and no significant change in urine formation. The results indicate that high blood fluoride levels interfere with generation of both Umax and TcH 2 O. These defects may be due to a washout of medullary solute or to a reduction in collecting duct permeability. The studies lend support to the contention that the concentrating defect associated with methoxyflurane may be due to inorganic fluoride, but do not prove such a relationship.