1. Innovative Research for a Sustainable Future www.epa.gov/research The Role of Dietary Zinc in Cadmium Nephrotoxicity Lin YS 1, Caffrey JL 2, Ho WC 3, Bayliss D 1, Sonawane B 1 1 U.S. Environmental Protection Agency, Office of Research and Development, USA 2 University of North Texas Health Science Center, Fort Worth, TX, USA 3 Institute of Environmental Health, China Medical University, Taichung, Taiwan Contact: Yu-Sheng Lin l email: Lin.Yu-Sheng@epa.gov l 703-347-0323 ABSTRACT INTRODUCTION RESULTS Background: Animal studies have shown that cadmium (Cd) and zinc (Zn) are associated with increased and decreased renal risk, respectively. Goal: To examine the joint effect of Cd exposure and Zn intake on renal risk. Methods: The data were obtained from 5,205 adults aged 50 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-94). Results: Logged urinary Cd is positively associated with albuminuria (odds ratio=1.29; p=0.01). Despite an apparent protective effect of Zn intake, the finding is not significant. However when considered jointly with Cd, there was a significant inverse association between albuminuria and the Zn-to-urinary Cd ratio (p<0.01). Discussion: Whereas Cd poses an important risk factor for albuminuria in older Americans, the positive role of Zn in moderating Cd-associated renal risk remains to be investigated. Exposure to Cd through Cd-contaminated foods (e.g., rice) and smoking is associated with increased renal risk. Once Cd enters the body, it displaces Zn stores from metallothionein. Metallothionein in turn buffers out Cd and thus, is believed to reduce toxicity through Cd sequestration. In addition to being essential to the function of metallothionein, Zn also plays a key role in protecting sulfhydryl groups from oxidative stress triggered by metals. Thus, it is hypothesized that Zn may moderate Cd-associated renal risk. Whereas Cd exposure is an important risk factor for albuminuria in elderly Americans, Zn intake may play a protective role by modifying Cd-induced nephrotoxicity. Additional studies are warranted to examine the mechanism(s) by which Zn moderates Cd-induced nephrotoxicity. 1.Briefel, R. R. et al. 2000. Zinc intake of the U.S. population: findings from the third National Health & Nutrition Examination Survey, 1988-94. J Nutr. 130:1367S-73S. 2.Institute of Medicine. 2001. Food and Nutrition Board, Dietary reference intakes for vitamin A, vitamin K, arsenic, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press. METHODS Demographic information was self-reported. Daily Zn intake for each individual was estimated by summing Zn intake from food, beverage and supplements (vitamins and mineral products) [1]. Zn RDA for men and women aged 19 years and older are 11 and 8 mg, respectively [2]. Urine Cd was analyzed by graphite furnace atomic absorption spectrometry. Urinary albumin was adjusted for creatinine (UACR, mg/mmol). Albuminuria was defined as UACR > 2.5 mg/mmol in men and > 3.5 mg/mmol in women. Logistic regression models were used for statistical analyses. DISCUSSION & CONCLUSIONS SELECTED REFERENCES Disclaimers : The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of their institutional affiliations including the U.S. Environmental Protection Agency. The authors declare they have no competing financial interests.