Jacob Fox1, Francesca Macaluso2, Camille Moore3, Elise Mesenbring4, Richard J Johnson5, Richard F Hamman6, Katherine A James7. 1. Colorado School of Public Health, Departments of Environmental & Occupational Health and Epidemiology, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: jafox2015@gmail.com. 2. Colorado School of Public Health, Departments of Environmental & Occupational Health and Epidemiology, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: francesca.macaluso@cuanschutz.edu. 3. Colorado School of Public Health, Departments of Environmental & Occupational Health and Epidemiology, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA; Center for Genes, Environment and Health, National Jewish Health, Smith Building; A647, 1400 Jackson Street, Denver, CO, 80206, USA. Electronic address: camille.moore@cuanschutz.edu. 4. Colorado School of Public Health, Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: elise.mesenbring@cuanschutz.edu. 5. School of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: richard.johnson@cuanschutz.edu. 6. Colorado School of Public Health, Departments of Environmental & Occupational Health and Epidemiology, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: richard.hamman@cuanschutz.edu. 7. Colorado School of Public Health, Departments of Environmental & Occupational Health and Epidemiology, University of Colorado Anschutz Medical Campus, Fitzsimons Building, 3rd Floor, 13001 E. 17th Place, B119, Aurora, CO, 80045, USA. Electronic address: kathy.james@cuanschutz.edu.
Abstract
BACKGROUND: Chronic kidney disease (CKD) is a cause of global morbidity and mortality in agricultural communities. The San Luis Valley (SLV) is a rural agricultural community in southern Colorado with geographic and sociodemographic risk factors for CKD, including a water supply contaminated by heavy metals. METHODS: We obtained pre-existing sociodemographic, clinical, and urine trace metal data for 1659 subjects from the San Luis Valley Diabetes Study, a prospective cohort study. We assessed prospective associations between urine tungsten (W) and time-to-CKD using accelerated failure time models (n = 1659). Additionally, logistic models were used to assess relationships between urine W and renal injury markers (NGAL, KIM1) using Tobit regression (n = 816), as well as epidemiologically-defined CKD of unknown origin (CKDu) using multiple logistic regression (n = 620). RESULTS: Elevated urine W was strongly associated with decreased time-to-CKD, even after controlling for hypertension and diabetes. Depending on how CKD was defined, a doubling of urine W was associated with a 27% (95% CI 11%, 46%) to 31% (14%, 51%) higher odds of developing CKD within 5 years. The relationship between urine W and select renal injury markers was not significant, although urine NGAL was modified by diabetes status. Elevated (>95%ile) urinary W was significantly associated with CKDu (OR 5.93, 1.83, 19.21) while adjusting for known CKD risk factors. CONCLUSIONS: Our data suggest that increased exposure to W is associated with decreased time-to-CKD and may be associated with CKDu. Given persistence of associations after controlling for diabetes and hypertension, W may exert a primary effect on the kidney, although this needs to be evaluated further in future studies.
BACKGROUND: Chronic kidney disease (CKD) is a cause of global morbidity and mortality in agricultural communities. The San Luis Valley (SLV) is a rural agricultural community in southern Colorado with geographic and sociodemographic risk factors for CKD, including a water supply contaminated by heavy metals. METHODS: We obtained pre-existing sociodemographic, clinical, and urine trace metal data for 1659 subjects from the San Luis Valley Diabetes Study, a prospective cohort study. We assessed prospective associations between urine tungsten (W) and time-to-CKD using accelerated failure time models (n = 1659). Additionally, logistic models were used to assess relationships between urine W and renal injury markers (NGAL, KIM1) using Tobit regression (n = 816), as well as epidemiologically-defined CKD of unknown origin (CKDu) using multiple logistic regression (n = 620). RESULTS: Elevated urine W was strongly associated with decreased time-to-CKD, even after controlling for hypertension and diabetes. Depending on how CKD was defined, a doubling of urine W was associated with a 27% (95% CI 11%, 46%) to 31% (14%, 51%) higher odds of developing CKD within 5 years. The relationship between urine W and select renal injury markers was not significant, although urine NGAL was modified by diabetes status. Elevated (>95%ile) urinary W was significantly associated with CKDu (OR 5.93, 1.83, 19.21) while adjusting for known CKD risk factors. CONCLUSIONS: Our data suggest that increased exposure to W is associated with decreased time-to-CKD and may be associated with CKDu. Given persistence of associations after controlling for diabetes and hypertension, W may exert a primary effect on the kidney, although this needs to be evaluated further in future studies.
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