Because the kidney is exposed to higher concentrations of fluoride than all other soft tissues (with the exception of the pineal gland), there is concern that excess fluoride exposure may contribute to kidney disease – thus initiating a “vicious cycle” where the damaged kidneys increase the accumulation of fluoride, causing in turn further damage to the kidney, bone, and other organs. This possibility is supported by a long line of human studies, as well as the following animal studies.

Kidney Damage in Fluoride-Exposed Animals (1 ppm):

“In the kidney, glomerular hypercellularity and mesangial proliferation was apparent in animals from both the NaF and AlF3 treatment groups. Congruent with the glomerular changes was deposition of protein in the tubules. There was a significant increase in the extent of monocyte infiltration in the animals treated with with AlF3 compared to controls… Histological evidence of glomerular distortions and other signs of kidney disorders were found in animals in both the AlF3 and NaF groups, although expressed differently. It is possible that physiological alterations in kidney function, not related to histological evidence of injury, were greater in the AlF3 group than the NaF group. The overall Al content of the kidneys in the AlF3 group was nearly double that found in the NaF and control groups. Since the kidney is critical to the elimination of both Na and Al, such alterations may have influenced the body burden of these elements, detoxification in general, as well as homeostasis of a variety of important ions, such as calcium.”
SOURCE: Varner JA, et al. (1998). Chronic administration of aluminum-fluoride and sodium-fluoride to rats in drinking water: Alterations in neuronal and cerebrovascular integrity. Brain Research 784: 284-298.

“The mean kidney enzyme activity rate was measured at 0.3863 for the control animals. In studies on experimental animals a marked reduction in kidney enzyme activity was noted in the 1 ppm group; it was measured at 0.2016 showing 47.8% decrease over the normal. Animals in the 5, 10, and 100 ppm groups showed no further ostensible inhibition in activity rate.”
SOURCE: Sullivan WD. (1969). The in vitro and in vivo effects of fluoride on succinic dehydrogenase activity. Fluoride 2:168-175.

“No gross lesions were found in the kidneys. Microscopic examinations were made on the kidneys from 6 animals which had not received fluoride in the drinking water, on 3 receiving 1 ppm, on 1 receiving 5 ppm, and on 6 receiving 10 ppm. Interstitial nephritis was observed in all the animals examined histologically, and the severity increased in proportion to the level of the sodium fluoride in the drinking water. Renal tubule hypertrophy and hyperplasia were found in those animals receiving sodium fluoride in the water but not in the 6 rats which had not been given sodium fluoride supplementation.”
SOURCE: Ramseyer WF, et al. (1957). Effect of sodium fluoride administration on body changes in old rats. Journal of Gerontology 12: 14-19.

Kidney Damage in Fluoride-Exposed Animals (5 ppm):

“[K]idneys of animals drinking water with containing 5 ppm fluoride showed certain cytochemical characteristics which may be interpreted in terms of deleterious metabolic effects in the kidneys, which excrete most of the fluorides from the organism. This is in agreement with some earlier reported observations that kidneys, more than other organs of the body, begin to show microscopic changes after prolonged daily ingestion levels of fluoride which may produce few gross changes other than fluoride storage in bones and teeth. Ogilvie (1948) showed that a dose of 7.5 mg of sodium fluoride given intraperitoneally each day for 100 days to rats produced morphological changes in the kidneys which included oedema in the interstitial connective tissue and increased vascularity of the glomeruli and medulla. These observations suggest that fluoride compounds cannot be treated as totally harmless when administered over long periods of time in relatively small concentrations… It is believed that the increased thirst and polyyuria observed in fluoridated animals is a result of functional changes in the kidneys… Our studies show a significant change in the activity of succinate dehydrogenase in the kidneys of the animals maintained on higher levels of fluoride in the drinking water.”
SOURCE: Manocha SL, et al. (1975). Cytochemical response of kidney, liver and nervous system to fluoride ions in drinking water. Histochemical Journal 7: 343-355.

Kidney Damage in Fluoride-Exposed Animals (10 ppm):

“Our study provides the first evidence that one of the effects of long-term F exposure is a change in expression of the plasma membrane and endoplasmic reticulum Ca++ pumps in the kidney. In summary, we provided rats with fluoride in their drinking water, which produced graded, plasma fluoride concentrations that occur in humans. Our studies showed that chronic high fluoride ingestion decreases the rate of Ca++ transport across renal tubule endoplasmic reticulum and plasma membranes, and reduced the amount of ER and PM Ca++ pump protein present in the kidney membranes. We conclude that chronic high fluoride ingestion may decrease the expression, increase the breakdown, or increase the rate of turnover of plasma membrane and endoplasmic reticulum Ca++ pump proteins and possibly other enzymes as well. The observed decreases in the rate of Ca++ transport and associated decreases in plasma membrane and endoplasmic reticulum Ca++ pump expression could affect in vivo Ca++ homeostasis.”
SOURCE: Borke JL, Whitford GM. (1999). Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes. Journal of Nutrition 129:1209-13.

Kidney Damage in Fluoride-Exposed Animals (>10 ppm):

“In summary, our study demonstrated that subchronic treatment with fluoride and/or acetaminophen in subtoxic doses induced oxidative and nitrosative stress in the liver and kidney of male and female rats.”
SOURCE: Inkielewicz-St?pniak I, Knap N. (2012). Effect of exposure to fluoride and acetaminophen on oxidative/nitrosative status of liver and kidney in male and female rats.  Pharmacol Reports 64(4):902-11.

“These results demonstrate that NaF induces the process of apoptosis in renal tubules via activation of the Bax expression and Bcl-2 suppression and this action is dose dependent; thus, apoptosis plays some role in the kidney injury induced by fluoride. Our data also suggest that OPN probably acts in a protective role against apoptosis in fluoride-treated renal cells.”
SOURCE: Xu H, et al. (2006). Effect of sodium fluoride on the expression of bcl-2 family and osteopontin in rat renal tubular cells. Biological Trace Element Research 109:55-60.

“An experiment was carried out on Sprague-Dawley rats (adult males) that for 50 days were administered, in the drinking water, NaF and NaF with caffeine (doses, respectively: 4.9 mg of NaF/kg body mass/24 h and 3 mg of caffeine/kg body mass/24 h). Disturbances were noted in the functioning of kidneys, which were particularly noticeable after the administration of NaF with caffeine. Changes in the functioning of kidneys were also confirmed by such parameters as the level of creatinine, urea, protein, and calcium. Modifications of the enzymatic antioxidative system (superoxide dismutase, catalase, and glutathione peroxidase) and lipid peroxidation (malondialdehyde) were also observed. Changes in the contents of the above parameters as well as pathomorphological examinations suggest increased diuresis, resulting in dehydration of the rats examined.”
SOURCE: Birkner E, et al. (2006). Influence of Sodium Fluoride and Caffeine on the Kidney Function and Free-Radical Processes in that Organ in Adult Rats. Biological Trace Element Research 109:35-48.

“This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first- and second-generation rat kidney tissues… Hydropic epithelial cell degenerations and moderate tubular dilatation were observed in some proximal and distal tubules. There were markedly focal mononuclear cell infiltrations and hemorrhage at some areas of the interstitium, especially at the corticomedullar junction. Mononuclear cell infiltrations were also evident in some peritubular and perivascular areas. Most of the vascular structures were congestive. Many Bowman capsules were narrowed. The severe degenerative changes in most of the shrunken glomerules and vascular congestion were also observed.”
SOURCE: Karaoz E, et al. (2004). Effect of chronic fluorosis on lipid peroxidation and histology of kidney tissues in first- and second-generation rats. Biological Trace Element Research 102:199-208.

“Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line… The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle’s loop.”
SOURCE: Cittanova ML, et al. (2002). Fluoride ion toxicity in rabbit kidney thick ascending limb cells. European Journal of Anaesthesiology 19(5):341-9.

“The purpose of this study was to assess renal damage in experimental fluorosis. Young albino rabbits were injected with 5, 10, 20, and 50 mg NaF/kg body weight/day for fifteen weeks and then sacrificed. No significant clinical signs of toxicity were found in animals exposed to the lowest dose. At the higher doses, however, the cytoachitecture of the kidneys exhibited increasing amounts of cloudy swellings, degeneration of tubular epithelia, tissue necrosis, extensive vacuolization in renal tubules, hypertrophy and atrophy of glomeruli, exudation, interstitial oedema, and interstitial nephritis. These changes in the kidneys result in impaired renal function in chronic fluoride intoxication.”
SOURCE: Shashi A, et al. (2002). Toxic effects of fluoride on rabbit kidney. Fluoride 35: 38-50.

“Fluoride nephropathy was exhibited as decreased fluoride excretion and appearance of urinary B2 microglobulin.”
SOURCE: Cao J, et al. (2001). Prevention of brick teas fluorosis in rats with low-fluoride brick tea on laboratory observation. Food & Chemical Toxicology 39: 615-619.

“The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was recognized between these F doses and renal tissue injury.”
SOURCE: Dote T, et al. (2000). Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-dose fluoride exposure. International Archives of Occupational and Environmental Health 73 Suppl:S90-2.

“Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.”
SOURCE: Guan ZZ, et al. (2000). Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis. Archives of Toxicology 74:602-8.

“Wistar rats were provided with distilled water containing NaF(100 mg/L), and were administered through gavage with Na2SeO3[0.1 mg/(kgBW.d)] and/or ZnSO4[14.8 mg/(kg BW.d)]. The results of biochemical, pathological and ultrastructural examinations showed that fluoride could cause serious renal impairments. The major damage induced by fluoride was epithelia of proximal renal tubules. The lipid peroxidation might be one of the mechanisms of fluoride toxicity. Na2SeO3 and ZnSO4 could antagonize the renal impairments induced by fluoride through their antioxidation. The cooperative effect of Na2SeO3 and ZnSO4 was more powerful than either Na2SeO3 or ZnSO4 alone.”
SOURCE: Xue C, et al. (2000). [Study on antagonistic effects of selenium and zinc on the renal impairments induced by fluoride in rats] Wei Sheng Yan Jiu 29(1):21-3.

“In kidney, focal intertubular mononuclear cell infiltration was observed even at the 79 ppm level. Besides, at 132 ppm, atrophied glomeruli with more periglomerula space were noticed. More pronounced changes like periglomerular fibrosis and tubular nephrosis were observed at 191 ppm F level.”
SOURCE: Kapoor V, et al. (1993). Effect of dietary fluorine on histopathological changes in calves. Fluoride 26: 105-100.

“At the higher dose (84 ppm in water), fluoride produced polyuria, polydipsia, and weight loss. Previous studies showed that fluoride is nephrotoxic and produces polyuria and polydipsia in the rat.”
SOURCE: Turner RT, et al. (1989). The effects of fluoride on bone and implant histomorphometry in growing rats. Journal of Bone and Mineral Research 4: 477-484.

“The effects of chronic fluoride excess in the mouse were studied by means of polarizing microscopy in combination with a special staining technique employing Sirius red F3B, a dye which renders collagen fibrils sharply visible. It was observed that changes occur in three renal areas: the interstitium, the intrinsic vasculature and Bowman’s capsule. The collagen content of each area increases after about 100 days of the total fluoride exposure… Although Bowman’s capsule was thickened, the glomerular tufts and the nephrons showed edematous swelling and degeneration. A concept is developed to illustrate how early inflammatory response to the chemical effects of fluoride excess leads to vascular injury, parenchymal ischemia and fibrosis.”
SOURCE: Greenberg SR. (1986). Response of the renal supporting tissues to chronic fluoride exposure as revealed by a special technique. Urologia Internationalis 41(2):91-4.

“marked renal toxicity was observed in postweaning rats treated on Day 29. The NaF exposure resulted in increased kidney weight and kidney/body weight ratio, profound diuresis, decreased urinary osmolality, and decreased ability to concentrate urine during water deprivation. Urinary chloride excretion was decreased for the first 2 days after NaF exposure, then increased in water-deprived rats 120 hr after treatment. Glucosuria and hematuria were present for 2 days after treatment with 48 mg/kg. Histological lesions were apparent in the proximal tubules of the treated Day 29 rats. Thus, the kidney of the suckling rat is largely unresponsive to NaF toxicity. Renal sensitivity increases abruptly after weaning in the Day 29 rat.”
SOURCE: Daston GP, et al. (1985). Toxicity of sodium fluoride to the postnatally developing rat kidney. Environmental Research 37:461-74.

“Dose related congestion of the duodenum, liver, kidney, and lung was observed in all animals. For the two higher doses, kidney degeneration and tubular necrosis were associated with glomerular inflammation. Serum fluoride had a dose related increase, while serum calcium and glucose concentrations showed initial dose dependent decreases. Diuresis was increased for the two higher doses on day 3 or 4 following treatment.. The authors conclude that acute fluoride poisoning in sheep induces severe disturbances of kidney and liver function as reflected by the altered activity of many enzymes.”
SOURCE: Kessabi M, et al. (1985). Experimental acute sodium fluoride poisoning in sheep: Renal, hepatic, and metabolic effects. Fundamentals of Applied Toxicology 7: 93-105.

“Activities of various enzymes were determined biochemically and histochemically in the liver and kidney of rats subjected for 10 mo. to fluoride (F-) concentrations of 0 (control), 10 (group 1) and 25 ppm (group 2) in drinking water. The activity of alkaline phosphatase, acid phosphatase and succinic dehydrogenase decreased. ATPase activity increased in liver and kidney of group 2 (25 ppm) animals. Lactic dehydrogenase activity also decreased but only in the kidney histochemically. Alterations in enzyme activities were pronounced in proximal and distal convoluted tubules of the kidney… F- interfered with intracellular metabolism in liver and kidney.”
SOURCE: Singh M, Kanwar KS. (1981). Effect of fluoride on tissue enzyme activities in rat: Biochemical and histochemical studies. Fluoride 14: 132-141.

“Effects in the kidneys are of the first to be seen in fluoride exposure of mammals. The reason for this is considered to be the relative high concentrations of fluoride found in the kidneys and in the urine during exposure.”
SOURCE: Hongslo CF, Hongslo JK, Holland RI. (1980). Fluoride sensitivity of cells from different organs. Acta Pharmacologica et Toxicologica 46:73-77..

“The present study assesses the effect of sodium fluoride administration on kidneys of mice. One hundred adult male Albino mice were fed 10 ppm (Group A), 500 ppm (Group B), and 1000 ppm (Group C) of sodium fluoride for 3 months… The most consistent changes in the kidneys were cloudy swelling of the tubular cells. In the highest dosage groups (B and C), sacrificed at the end of three months, we found marked necrosis of tubular cells, atrophy of the glomeruli, and areas of interstitial infiltration of round cells. It is concluded that kidneys are adversely affected by prolonged use of sodium fluoride.”
SOURCE: Kour K, Singh J. (1980). Histological findings in kidneys of mice following sodium fluoride administration. Fluoride 13: 163-167.

“In summary, Fischer 344 rats pretreated with NaF or anesthetized with methoxyflurane showed more diuresis and natriuresis than did control animals. Urinary osmolarity was lower in the fluoride-treated group. Free water reabsorption was markedly reduced, while free water excretion was not significantly altered by pretreatment with fluoride. The results suggest that NaF and methoxyflurane alter renal function primarily by inhibiting active chloride transport in the ascending limb of Henle’s loop.”
SOURCE: Roman RJ, et al. (1977). Renal tubular site of action of fluoride in Fischer-344 rats. Anesthesiology 46: 260-264.

“In the present study, evidence was obtained which indicated a close relationship between polyuria and changes in certain urinary ion excretion in fluorosis. The maximum increase in urine volume occurred during the first day following treatment. Polyuria was accompanied by significant increases in urinary K+, Na+, Mg2+, Ca2+, and inorganic phosphate… In our experiments, mitochondrial ATPase in the kidney was found to be decreased by the dose of fluoride tested. To our knowledge, this is the first report on the in vivo effects of fluoride on renal (Na+ K+)-ATPase activity. The decrease in activity is apparently responsible for urinary Na+ loss and a decrease in serum Na+. In addition fluoride treatment also resulted in a significant decrease in (Ca2+ Mg2+)-ATPase activity which can be held responsible for the increase in urinary Ca2+.”
SOURCE: Suketa Y, Mikami E. (1977). Changes in urinary ion excretion and related renal enzyme activities in fluoride-treated rats. Toxicology and Applied Pharmacology 40: 551-9.

“In the Sprague-Dawley rats, during moderate fluoride administration (120 umol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased… During larger daily doses of fluoride (240 umol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin.”
SOURCE: Wallin JD, Kaplan RA. (1977). Effect of sodium fluoride on concentrating and diluting ability in the rat. American Journal of Physiology 232: F335-40.

“Frascino et al (1970, 1972) studied the effects of inorganic fluoride on the renal concentration mechanisms in dogs. The high blood fluoride levels interfere with both the generation of maximally concentrated urine and tubular free water reabsorption.”
SOURCE: Gottlieb LS, Trey C. (1974). The effects of fluorinated anesthetics on the liver and kidneys. Annual Review of Medicine 25: 411-429.

“Supplemental fluoride lowered both the urinary calcium and phosphorus concentrations. The lowering of urinary calcium concentration was due to a dilution of excreted calcium by a fluoride-induced polyuria, since dietary sodium fluoride did not reduce the urinary calcium excretion (% of intake)… The polyuria induced by fluoride was accompanied by an enhanced sodium excretion and a decrease in osmolality. These results were consistent with previous findings that the administration of fluoride caused polyuria in laboratory animals. Further, the renal sodium gradient was markedly reduced in the fluoride-induced diuretic rat.”
SOURCE: Hamuro Y. (1972). Relationship between prevention of renal calcification by fluoride and fluoride-induced diuresis and reduction of urinary phosphorus excretion in magnesium-deficient KK mice. Journal of Nutrition 102: 893-900.

“The present findings indicate that 50 uM plasma fluoride results in a definite increase in rate of urine flow and are consistent with the estimate made from the experience of Goldemberg in humans. The present findings also agree with the data from 3 patients who had received methoxyflurane anesthesia. Two of these patients had inorganic serum fluoride concentrations of 20 to 30 uM and no obvious diuresis; whereas the patient with a concentration of 275 uM had marked polyuria. The agreement lends further weight to the suggestion that metabolism of methoxyflurane to inorganic fluoride is a major factor in the nephrotoxicity noted after anesthesia with methoxyflurane.”
SOURCE: Whitford GM, Taves DR. (1971). Fluoride-induced diuresis: Plasma concentrations in the rat. Proceedings of the Society for Experimental Biology and Medicine 137:458-460.

“the kidneys were abnormal in most of the animals given fluorides, with the most severe changes associated with the highest doses and longest survival periods. In addition to the previously well-known dilatation of the renal loops and ducts, PAS-positive casts were seen in pronounced cases in many dilated ducts and also typical granlulomas in the medullo-cortical zone and occasionally in the outer part of the cortex.”
SOURCE: Poulson H, Ericcson Y. (1965). Chronic toxicity of dietary sodium monofluorophosphate in growing rats, with special reference to kidney changes. Acta pathologica et microbiologica Scandinavica 65: 493-504.

“The renal lesions seen in rats ingesting 200-500 ppm fluoride in the water for 5 days were: (1) necrosis of the tubular cells, and (2) a dilatation of the tubules especially in the corticomedullary region. Neither lesion occurred in all the rats examined; necrosis was seen more often than tubular dilatation. The tubular dilatation was similar to the lesion seen in a few rats after single, large doses of sodium fluoride (Taylor et al., 1961) and to the lesion described by Pindborg (1957) after feeding 0.05% sodium fluoride in the diet for 21-28 days… The ingestion of fluoride levels of 1-50 ppm for 6 months did not produce renal lesions in the rat. A level of 100 ppm fluoride for this period of time caused dilatation of the renal tubules in two of 12 rats.”
SOURCE: Taylor JM, et al. (1961). Toxic effects of fluoride on the rat kidney. II. Chronic effects. Toxicology and Applied Pharmacology 3:290-314.

“All animals in group 2, which received the fluoride throughout the entire experimental period, revealed kidney changes histologically typical of chronic fluoride intoxication… The sequence of the changes in the “fluorosed kidney” is dilation of the Henle loops, followed by dilation of the convoluted tubules and later by inflammation. During the recovery process the dilation disappeared first, followed by a slower reduction of inflammation. As would be expected the amount of fibrosis was unchanged. Finally, it should be mentioned that a year after the cessation of excessive fluoride diet a minority of rats still had dilated Henle loops and convoluted tubules. In these cases the interstitial inflammation and fibrosis were most pronounced. It remains for future research to establish how much fluoride it is possible to give rats without creating irreversible kidney changes.”
SOURCE: Lindemann G, et al. (1959). Recovery of the rat kidney in fluorosis. Archives of Pathology 67: 30-33.

“Two hundred and twenty-six white rats were given a diet containing 0.05 per cent sodium fluoride (226 ppm) for periods ranging from 3 to 56 days. It was established that changes in the kidneys occured regularly after 21-28 days on the diet… The kidney changes consisted primarily in dilatation of the Henle loops in the juxtacortical area of the medulla, soon followed by a flattening of the epithelium in the convoluted tubules in the cortex and a distention of the tubules, possibly due to some kind of ‘stop’ in the Henle loops.”
SOURCE: Pindborg JJ. (1957). The effect of 0.05 per cent dietary sodium fluoride on the rat kidney. Acta pharmacolgica et toxicologica 13: 36-45.

‘In previous papers, the author reported impairment of renal function due to fluorosis. The current study presents morphological renal changes of rabbits and young albino rats due to fluorosis… On gross examination, no marked changes were observed. However, in both groups which had been given 30 and 50 mg of NaF per kg of body weight, inflammatory changes in the glomeruli with increased cellularity, capillary hyperemia, exudation, hypertrophy or atrophy, tubular degeneration with cloudy swelling, vascular degeneration and protein casts or blood in the tubular lumens were seen microscopically… The above-mentioned morphological changes, combined with impairment of renal function described in the previous reports, indicate that fluoride causes serious damage to kidneys.”
SOURCE: Kawahara H. (1956). Experimental studies on the changes of the kidney due to fluorosis. Part III. Morphological studies on the changes of the kidney of rabbits and growing albino rats due to sodium fluoride. Shikoku Acta Medica 8:283-28. (Abstracted in: Fluoride 1972; 5:50-53.)

“In previous papers the author reported disturbances of renal function, especially changes in the urine, serum NPN, serum creatinine and serum chlornatrium of rabbits due to ingestion of fluoride. The current investigation deals with the effect of sodium fluoride on renal clearance, particularly on plasma urea clearance, on renal plasma flow (RPF) and glomerular filtration rate (GFR) in rabbits… The authors concluded from the experimental data presented here that the administration of fluoride in the above doses impairs the kidney function.”
SOURCE: Kawahara H. (1956). Experimental studies on the changes of the kidney due to fluorosis. Part II. Influence of sodium fluoride on renal clearance in rabbits. Shikoku Acta Medica 8:273-282. (Abstracted in: Fluoride 1972; 5:48-50.)

“The following experiments were conducted in order to determine possible renal changes by fluoride. Mature male rabbits weighing over 1.5 kg were given orally 1%, 3%, 5% sodium fluoride solutions which provided 10, 30 and 50 mg respectively of sodium fluoride per kg body weight… The above results or urine and blood suggest that renal damage occurs in fluorosis.”
SOURCE: Kawahara H. (1956). Experimental studies on the changes of the kidney due to fluorosis. Part I: Influence of sodium fluoride on the urine changes and non-protein nitrogen, creatinine and sodium chloride in serum of rabbits. Shikoku Acta Medica 8:266-272. (Abstracted in: Fluoride 1972; 5:46-48.)

“Rats given small amounts of NaF in the diet exhibited, in addition to the well-known skeletal and dental fluorosis, marked polydipsia and polyuria… The histological examination indicated that in the kidneys there was a vascular, glomerular and more obviously tubular degeneration leading finally to interstitial fibrosis.”
SOURCE: Bond AM, Murray MM. (1952). Kidney function and structure in chronic fluorosis. British Journal of Experimental Pathology 33: 168-176.

“The only organ found to be changed macroscopically was the kidney… The kidneys all had the same appearance, being contracted and paler in colour than normally; the surface was irregular, in most cases granulated. Only some of the rats displayed macroscopic kidney changes of this kind… Under the microscope the kidneys of Rats 4,5,6,10,11,21,22,25 all showed signs of a chronic, mostly interstitial nephritis of uniform character; the changes were slight in Rats 5 and 6, which had not shown macroscopic changes, pronounced in the others… The changes in the kidney of Rat 21 are described below as being typical: The kidney is contracted, the surface very uneven. The changes are diffusely spread. Many glomeruli show serous or hyaline degeneration. The lumina of tubuli in most cases are irregularly dilated; this often forms cystic areas with an abundant serous content. Epithelium in the tubuli is low but well preserved. Universally there is proliferous development of connective tissue; the tissue is hyperaemic and contains scattered round-cell infiltration. A slight calcification in the tissue is observed in one place. Vessels normal.”
SOURCE: Roholm, K. (1937). Fluorine Intoxication. London: Lewis p 219.