THE EFFECT OF SODIUM-FLUORIDE AT PROPHYLACTIC AND TOXIC DOSES ON RENAL STRUCTURE AND FUNCTION IN THE ISOLATED-PERFUSED RAT-KIDNEY

To assess the renal effects of fluoride, isolated rat kidneys were per fused in single pass mode for 120 min. Five, 15 and 50, as well as 150 , 500 and 1500 mu mol NaF were administered 60, 80 and 100 min after s tarting the perfusion, respectively. Kidneys were perfused with consta nt pressure (100 mmHg). The perfusate consisted of a substrate supplem ented Ringer solution containing hydroxy ethyl starch (HES) to produce isoncotic conditions. Concentrations below 500 mu mol/l NaF did not i nduce major changes in the main parameters of renal function. Only upo n admixture of the highest concentration of 1500 mu mol/l NaF severe c hanges in renal function could be observed, resulting in complete anur ia and a drastic reduction of renal perfusion to 5% of control, associ ated with a cessation of glomerular filtration. Due to the lack in tub ular load, tubular reabsorptive processes inevitably declined to zero. The morphological analysis of kidneys exhibited to 500 mu mol/l NaF r evealed the occurrence of vesicular material within the urinary space. These vesicles could electron microscopically be identified as membra ne enclosed material of podocytic origin. The interstitium was widened . Upon admixture of 1500 mu mol/l NaF, kidneys responded with a decrea se of the interstitial space. Moreover, epithelial cell swelling, hydr opic degeneration of all proximal and distal tubular segments, bleb fo rmation and intraluminal casts were observed frequently. Glomerular ca pillaries were filled with fine precipitates and their endothelium was severely damaged. The results of our studies in the isolated perfused rat kidney (IPRK) model clearly demonstrate a direct dose dependent a cute nephrotoxic effect of NaF only for extremely high doses, which, h owever, may be reached in human cases of severe fluoride intoxication. On the contrary, for low fluoride doses, especially for those concent rations occurring in human plasma upon cariesprophylactic intake of fl uorides, no signs of direct acute nephrotoxic action could be observed in the IPRK model.