Objectives/Goals: We evaluated the associations of urine uranium with incident chronic kidney disease (estimated glomerular filtration rate 30 mg/g), and baseline and follow-up plasma metabolite levels in participants without diabetes across the Great Plains and Southwest. Methods/Study Population: We evaluated participants with available urine uranium estimates, eGFR, uACR, and other variables of interest. In incident case analyses, participants were free of CKD (N=1,845) and albuminuria (1,693) at baseline (2001-2003). We used generalized estimating equations, clustering on family identifier, to estimate risk ratios (RRs) of incident CKD and albuminuria per doubling of urine uranium adjusted for sex, age, eGFR or uACR, study center, educational level, smoking status, BMI, and arsenic exposure. Nontargeted metabolomic profiling was analyzed by gas chromatography-mass spectrometry. In metabolome-wide association analyses, we used adjusted linear mixed models to estimate the association of urine uranium (N=1,223) with relative changes in metabolite concentrations over time. Results/Anticipated Results: Overall, the median (IQR) age was 35.9 (23.7, 46.8) years and 60% participants were female. The number of incident CKD cases was 28 (mean follow-up 5.6 years), and the number of albuminuria cases was 140. The adjusted RR (95% CI) per doubling of urine uranium was 0.90 (0.71, 1.15) for incident CKD and 1.00 (0.92, 1.08) for incident albuminuria. In metabolome-wide analyses, urine uranium was associated with a relative change in 8 unique metabolites and 31 unknown metabolomic features (p-value <0.05), with 5 unique metabolites (threonic acid, N-acetylornithine, isocitric acid, cellobiose, and 6-deoxyglucose) and 7 unknown metabolomic features reaching false discovery rate significance (BH-adjusted p-value <0.05). Discussion/Significance of Impact: Urine uranium was not associated with incident CKD nor with albuminuria. We identified 5 unique metabolites associated with urine uranium. Our findings are relevant for uranium-related kidney disease in people without diabetes, but require additional confirmation due to potential reverse causality and lack of drinking water uranium exposure.
Patterson et al. (Wed,) studied this question.