Fluoride renal clearance: a pH-dependent event.

The renal clearance of fluoride (CF) was studied in pentobarbital-anesthetized rats. Urine flow rate and chloride clearance, previously thought to be the main determinants of CF, were readily dissociated from CF. Neither the clearance of sodium nor the excretion of potassium correlated consistently with CF. In experiments designed to manipulate urinary pH, viz., the administration of NaHCO3 or NH4Cl, acetazolamide, and mannitol, CF correlated closely with urinary pH. At a urinary pH of 5.0-k96, CF/GFR averaged less than 5%, while at a urinary pH of approximately 7.6, mean CF/GFR exceeded 65%. The data suggest that 35-45% of the filtered fluoride is reabsorbed in the proximal tubule, regardless of the final urinary pH, while in acidosis the majority of fluoride reabsorption occurs in the distal nephron. The results suggest that the tubular reabsorption of fluoride is inversely related to tubular fluid pH. Fluoride reabsorption seems to occur by nonionic diffusion, apparently as hydrogen fluoride. Depending on local pH gradients, it may occur along the entire nephron.