Role of renal function in the association of drinking water fluoride and plasma fluoride among adolescents in the United States: NHANES, 2013-2016

Context: While fluoride has been added to drinking water and dental products for decades in order to prevent tooth decay, there are growing concerns about its potential toxicity. Given that fluoride is primarily excreted in urine, an important question that has not been examined is whether among those whose drinking water is fluoridated, impaired renal function is associated with higher levels of circulating fluoride. Objective: To examine the association between drinking water and plasma fluoride and its modification by renal function. Design, Setting, and Participants: Participants in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 with measures of fluoride in plasma and drinking water and renal function. These measures were only available in adolescent age 12-19 years. Outcomes: Plasma fluoride levels and their modification by strata of renal function, measured by the estimated glomerular filtration rate (eGFR). Results: Among 1841 healthy adolescents, a 10 ml/min/1.73 m (Penman et al., 1997) lower eGFR and a 1 mg/L higher drinking water fluoride concentration were associated with a 0.02 (95%CI -0.02, -0.03) umol/L and 0.23 (95%CI 0.15,0.30) umol/L higher adjusted plasma fluoride level, respectively. The association of water and plasma fluoride levels was most robust among those with lower renal function (multiplicative interaction p value < 0.001). For adolescents in the lowest eGFR quartile, a 1 mg/L higher drinking water fluoride concentration was associated with a 0.35 (95%CI 0.21,0.48) umol/L higher plasma fluoride level, compared to 0.20 (95%CI 0.14,0.26) umol/L in the highest eGFR quartile. Restriction to those with measurable plasma fluoride levels yielded similar results. Conclusions: Water fluoridation results in higher plasma fluoride levels in those with lower renal function. How routine water fluoridation may affect the many millions of Americans with Chronic Kidney Disease, who are particularly susceptible to heavy metal and mineral accumulation, needs to be further investigated.