Abstract
We assessed the association of three chlorinated dibenzo- p -dioxins, a chlorinated dibenzofuran, and four dioxin-like polychlorinated biphenyls (PCBs) in human blood with nephropathy (microalbuminuria or macroalbuminuria) among teens and young adults (12–30 years old) having normal glycohemoglobin (A1c <5.7%). The data were derived from the 1999–2004 National Health and Nutrition Examination Survey (unweighted n=1504, population estimate=38,806,338). In this paper, nephropathy refers to normal A1c with nephropathy. In an all-adult sample (Everett CJ, Thompson OM. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy? Environ Res 2014;132:126–31), the cut-offs for these chemicals being considered elevated, were defined as the 75th percentile. Using these same cut-offs again, the proportion of those with one or more of the eight dioxin-like compounds elevated was 9.9%. The four chemicals associated with nephropathy were 1,2,3,6,7,8-hexachlorodibenzo- p -dioxin, PCB 126, PCB 169, and PCB 156. The proportion with one or more of these four dioxin-like chemicals elevated was 3.9% (unweighted n=46) and the odds ratio (OR) for nephropathy was 7.1 [95% confidence interval (CI) 1.8–28.1]. The association was strong among females (OR 17.4, 95% CI 3.4–88.6), but among males there were no cases of nephropathy when one or more of the four dioxin-like chemicals were elevated, and therefore no association. In a separate analysis, elevated toxic equivalency, defined using the eight dioxin-like chemicals (TEQ 8 ), was associated with nephropathy. TEQ 8 ≥50.12 fg/g included 2.6% of the sample (unweighted n=28) and had an OR of 5.8 (95% 1.3–25.9) for nephropathy. As found in the analysis of one or more of four dioxin-like chemicals elevated, TEQ 8 ≥50.12 fg/g was associated with nephropathy among females (OR 11.9, 95% CI 1.6–87.2), but not males. Trends for least-squares means also differed by gender, but there were no significant differences in mean TEQ 8 between normal subjects and those having nephropathy in either males or females. We also evaluated pre-diabetes (A1c 5.7–6.4%) without nephropathy and found no associations when one or more of four dioxin-like compounds were elevated, or when TEQ 8 was ≥50.12 fg/g. In this study, associations of dioxin-like chemicals with nephropathy were found among females at an early age. Prospective studies are needed to determine if dioxin-like compounds cause nephropathy, or if these relationships are cases of reverse causation.