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 animal research, as well as two types of human studies: (1) studies of kidney function in individuals with skeletal fluorosis and/or elevated fluoride exposure, and (2) studies on the effects of high temporary peaks in fluoride exposure following anesthesia with fluorinated chemicals.


“This study provides new insights that inorganic fluoride intake can cause a considerable nephrotoxic effect on human proximal tubular cells, but this toxicity depends strongly on Na+ and Ca2+ activities.”
SOURCE: Chandrajith R, et al. (2011). Dose-dependent Na and Ca in fluoride-rich drinking water–another major cause of chronic renal failure in tropical arid regions. Sci Total Environ. 409(4):671-5.

“Interestingly, the CKDue [chronic kidney disease of unknown etiology] prevalent regions in the country overlap with the high groundwater fluoride zone of Sri Lanka suggested by Dissanayake (1996), indicating that at least to some extent, the fluoride content of drinking water may contribute to the CKDue in Sri Lanka.”
SOURCE: Chandrajith R, et al. (2011). Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health 33(3):267-78.

“OBJECTIVE: To explore the dose-effect relationship of water fluoride levels and renal damage in children and observe the difference of renal function between high-loaded fluoride people and dental fluorosis people in the same water fluoride level region. METHODS: 210 children were divided into seven groups in term of drinking water fluoride levels and whether they suffered from dental fluorosis. Fluoride concentrations in urine and serum and activities of urine NAG and gamma-GT were determined. RESULTS: The urine and serum fluoride of high-loaded fluoride people and dental fluorosis people increased compared with control, moreover fluoride contents in urine and serum increased gradually with the increase of fluoride level in drinking water. Urine NAG and gamma-GT activities significantly increased in dental fluorosis people from area of 2.58 mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L fluoride in drinking water. Moreover, there existed an obvious dose-effect relationship between the drinking water fluoride concentration and NAG and gamma-GT activity. CONCLUSION: Over 2.0 mg/L fluoride in drinking water can cause renal damage in children, and the damage degree increases with the dinking water fluoride content. Renal damage degree is not related to whether the children suffered from dental fluorosis and mainly due to water fluoride concentration.”
SOURCE: Liu JL, Xia T, Yu YY, Sun XZ, Zhu Q, He W, Zhang M, Wang A. (2005). [The dose-effect relationship of water fluoride levels and renal damage in children] Wei Sheng Yan Jiu. 34(3):287-8.

“Evidence of chronic fluoride intoxication, associated with renal tubular dysfunction in the group of FMBD patients, brings to focus the possibility that fluoride toxicity may be responsible for both bone and kidney disease in FMBD… Evidence is available in the literature to support our observation of fluoride-induced renal damage.”
SOURCE: Harinarayan CV, et al. (2006). Fluorotoxic metabolic bone disease: an osteo-renal syndrome caused by excess fluoride ingestion in the tropics. Bone 39: 907-14.

“Renal function especially glomerular filtration rate was very sensitive to fluoride exposure. Inorganic phosphate concentrations in urine were significantly lower in the residents in fluorosis areas in China than in non-fluorosis area in China and Japan…. The results show that exposure to excess fluoride has caused dental/skeletal fluorosis and reduced glomerular filtration rate in the residents living in fluorosis areas..”
SOURCE: Ando M, et al. (2001). Health effects of fluoride pollution caused by coal burning. Science of the Total Environment 271(1-3):107-16.

“We report a case of fluoride intoxication related to potomania of Vichy water, a highly mineralized water containing 8.5 mg/L of fluoride. Features of fluoride osteosclerosis were prominent and end-stage renal failure was present. The young age of the patient, the long duration of high fluoride intake, and the absence of other cause of renal insufficiency suggest a causal relationship between fluoride intoxication and renal failure.”
SOURCE: Lantz O, et al. (1987). Fluoride-induced chronic renal failure. American Journal of Kidney Disorders 10(2):136-9.

“Kidney damage (1) in distal and proximal tubular function, (2) in glomerular filtration, occurred in 40 to 60 year olds residing in El Quel an endemic fluorosis area in Southern Algeria compared to normals from Algiers. Functional renal disturbances are proportional to the degree of fluoride accumulation which incrases in relation to: a) the level of fluoride in drinking water, b) the fluoride level in nails and c) the radiological grade (O I II III) of fluorosis.”
SOURCE: Reggabi M, et al. (1984). Renal function in residents of an endemic fluorosis area in southern Algeria. Fluoride 17: 35-41.

“Complete urine examinations including urea, creatinine and fluoride clearances were carried out on 25 cases of endemic fluorosis… In 10 healthy nonfluorotic subjects urea, creatinine and fluoride clearances were measured simultaneously as a control. The following results were obtained: The mean values for maximum urea clearance and standard urea clearance were low compared to mean control values. The decline in creatinine and fluoride clearances compared to the controls was statistically significant, an indication that chronic fluoride intoxication leads to a distinct impairment of glomerular function in human beings.”
SOURCE: Jolly SS, et al. (1980). Kidney changes and kidney stones in endemic fluorosis. Fluoride 13: 10-16.

“In my medical practice I have encountered two cases in which fluoridated water interfered with kidney function. One of these, Miss G.L., 27 years old, had been under my care from July 1966 to September 1969 for allergic nasal and sinus disease. She had a congenital cystic kidney necessitating consultation with a urologist. As shown by its inability to excrete indigo carmine, a dye employed as an indicator of kidney function, the left kidney was not working and was slated for removal. This patient also reported having pains and numbness in arms and legs, spasticity of the bowels, ulcers in the mouth, headaches, and a progressive general disability – symptoms of possible intolerance to fluoride – for about 15 years. Her water supply (Highland Park, Michigan) had been fluoridated since September 1952. On February 1, 1967, I instructed her to avoid fluoridated water for drinking and cooking. Within a few weeks all the above-mentioned symptoms disappeared, and another kidney dye test on June 12, 1967, astonishingly revealed that the left kidney had begun to function again! A follow-up 5 years later revealed that the patient had remained in good health as long as she refrained from drinking fluoridated water.
The other patient, Mrs E.P., 39 years old, who visited me on August 25, 1969, who visited me on August 25, 1969, had advanced pyelitis of the left kidney, beginning with osteosclerotic changes in the pubic bones, and exostosis at the sternum, accompanied by the same clinical picture as in the patient just discussed. The function of the diseased kidney and the other symptoms improved markedly within six weeks after she stopped drinking the municipal water in Midland, Michigan (fluoridated since January 1946). Twenty-four hour urinary fluoride excretions before and after the tests were 2.39 and 4.20 mg, respectively. For most of her life she had resided in Lubbock, Texas (water supply fluoride then 4.4 ppm). The development of osteosclerosis in this case was not surprising, since – as recorded in fluoridated Evanston, Illinois, and also in a fluoridated Finnish community – kidney patients retain as much as 60% more fluoride than do persons in normal health. In the Finnish work blood fluoride levels were 3 to 4 times higher than normal in the patients with renal disorders.”
SOURCE: Waldbott GL, et al. (1978). Fluoridation: The Great Dilemma. Coronado Press, Inc., Lawrence, Kansas. pp. 155-156.

“The kidney function of 25 radiologically proven cases of endemic fluorosis was studied at the Medical College of Patiala. Evidence of statistically significant decrease in creatinine clearance is presented. Some structural abnormalities in kidneys have been described. No significant tubular abnormalities could be demonstrated by water loading and water deprivation tests.”
SOURCE: Singla VP, et al. (1976). The kidneys. Fluoride 9: 33-35.

“The question is whether the chronic excessive fluoride intake caused the renal damage (either directly or indirectly) or whether the systemic fluorosis was due to impaired renal function.”
SOURCE: Juncos LI, Donadio JV Jr. (1972). Renal failure and fluorosis. Journal of the American Medical Association 222(7):783-5.

“The distribution of findings suggestive of not-normal genitourinary conditions was approximately the same for the fluoride-exposed group and the control group except for the incidence of albuminuria which was found to be higher in the exposed group. This finding and its distribution in the subgroups suggest the possibility of a relationship between fluoride exposure and increased excretion of albumin in the urine.”
SOURCE: Derryberry OM, et al. (1963). Fluoride exposure and worker health. Archives of Environmental Health 6: 503-511.

“There is evidence from animal experiments that fluoride in large amounts causes gross alterations of renal structure and decreased tubular function. Injury with necrosis of the columnar cells lining the proximal convoluted tubules is the primary lesion… Kidney function tests were done in 28 of our cases. Blood urea ranged from 15 to 20 mg/100 ml with an average of 33. Urea clearance was done in only six cases and showed impaired function in five. The ratio of the concentration of inorganic phosphorous excreted in the urine to that in the serum is approximately 50 in normal subjects. This value increases with renal insufficiency. It averaged 67 in our cases. We found significant aminoaciduria in 4 cases. The concentration and dilution tests were essentially normal. Other kidney function tests were not done, but the existence of aminoaciduria, slightly increased blood urea, impairment of urea clearance, and a high phosphorus ratio as described all suggest a subtle disturbance of kidney function which needs further elaboration.”
SOURCE: Singh A, et al. (1963). Endemic fluorosis. Epidemiological, clinical and biochemical study of chronic fluoride intoxication in Punjab. Medicine 42: 229-246.

“Of the 19 patients in the series, 12 were examined for the presence of albuminuria, and this was found to be present in 11. The urinary excretion of fluorine damages the kidney, which results in the common finding of albuminuria… Renal damage does appear to be a frequent occurrence and is probably due to the excretion of fluorine, analagous to renal damage caused by heavy metals.”
SOURCE: Kumar SP, Harper RA. (1963). Fluorosis in Aden. British Journal of Radiology 36: 497-502.

“Urea Clearance Test: This test (Van Slyke method) was performed in fourteen cases… The results showed marked impairment of renal function. The mean figures for the maximum and standard clearance were 26.24 and 39.67% of the normal respectively.”
SOURCE: Siddiqui AH. (1955). Fluorosis in Nalgonda district, Hyderabad-Deccan. British Medical Journal ii (Dec 10): 1408-1413.

“Osteosclerosis may be a dangerous sequel to the chronic ingestion of fluorine-containing water supplies, since it may give rise to a secondary anemia due to encroachment upon the blood-forming marrow. There is also the possibility of kidney damage due to chronic fluoremia.” 
SOURCE: Linsman JF, McMurray CA. (1943). Fluoride osteosclerosis from drinking water. Radiology 40: 474-484.

“Renal function was tested by determination of the filtration rate, blood urea clearance, uric acid clearance, and chloride clearance. (a) Filtration rate – … In six cases, the filtration rate was below the normal lower limit and in three cases was within normal limits or above. (b) Blood urea clearance – This was estimated by van Slyke’s method. In all the cases the figures were below the normal lower limit and in some very much below the limit. The filtration rate and blood urea clearance values show that, in the majority of the cases, kidney function is impaired, in some markedly so.”
SOURCE: Shortt HE, et al. (1937). Endemic fluorosis in the Madras presidency. Indian Journal of Medical Research 25: 553-568.

Kidney Effects in Humans Receiving Fluorinated Anesthesia:

“In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. Based upon the clinical experience with methoxyflurane, serum fluoride concentrations exceeding 50 mumol/l were considered to be nephrotoxic.”
SOURCE: Nuscheler M, et al. (1996). [Fluoride-induced nephrotoxicity: fact or fiction?]. Anaesthesist 45 Suppl 1:S32-40.

“Evidence for fluoride nephrotoxicity has accumulated largely from the adverse effects of halogenated anesthetics on renal function.”
SOURCE: Partanen S. (2002). Inhibition of human renal acid phosphatases by nephrotoxic micromolar concentrations of fluoride. Experimental and Toxicologic Pathology 54(3):231-7.

“The predominant factors in the production of methoxyflurane nephrotoxicity appear to be high methoxyflurane dosage and serum inorganic fluoride concentration.”
SOURCE: Mazze RI. (1976). Methoxyflurane nephropathy. Environmental Health Perspectives 15:111-9.

“Kidney damage can appear within a few days following methoxyflurane anesthesia. This phenomenon was studied by Cousins and Mazze (1973), who reported that peak (i.e. transient) post-anesthesia plasma F- levels in afflicted humans exceeded 90 umol/l. The nephrotoxicity was accompanied by an increased urine volume of low osmolarity, and increased thirst, with the syndrome tending to obey a short-term dose-response pattern in man. Mazze et al. (1972) and Cousins et al. (1974) have shown that kidney damage in rats exposed to methoxyflurane was caused by high inorganic fluoride concentrations and not by oxalic acid, which is also a metabolic breakdown product of methoxyflurane. Taves et al. (1972) also related the nephrotoxicity and polyuria to the metabolically released inorganic fluoride.”
SOURCE: Marier J, Rose D. (1977). Environmental Fluoride. National Research Council of Canada. Associate Committe on Scientific Criteria for Environmental Quality. NRCC No. 16081.