Abstract
The usage of glyphosate is increasing worldwide. Glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern in unknown chronic kidney disease (CKDu). As with Cd and other elements, glyphosate exposure has been reported as risk factor for CKDu in farmers. This study aimed to evaluate the influence of co-exposure to glyphosate and metals or metalloids in chronic kidney disease (CKD). In this study, the urine samples from 55 patients with CKD and 100 participants without CKD were analyzed for glyphosate, arsenic (As), cadmium (Cd), and lead (Pb) concentrations, and estimated glomerular filtration rate (eGFR). Negative associations between glyphosate, AMPA, As, and Cd concentrations in the urine and eGFR were found for study subjects (p < 0.05). With regard to the effect of co-exposure, the odds ratios (OR) for subjects with an eGFR of < 60 mL/min/1.73 m2 was significant because of the high Cd concentration (> 1 μg/g creatinine; OR = 7.57, 95% CI = 1.91–29.95). With regard to the effect of co-exposure, the OR for subjects with an of eGFR < 45 mL/min/1.73 m2 was significant at high glyphosate concentration (> 1 μg/g creatinine; OR = 1.57, 95% CI = 1.13–2.16) and As concentration (> 1 μg/g creatinine; OR = 1.01, 95% CI = 1.00–1.02). These results showed that glyphosate, AMPA, As, and Cd have an effect on CKD; notably, Cd, As, and glyphosate exposure can be important risk factors after stage 3a of CKD, and that there was a co-exposure effect of As and glyphosate in CKD after stage 3b. The potential health impacts of glyphosate should be considered, especial for patients with CKD and eGFR below 45 mL/min/1.73 m2.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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We are in great debt to Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital for sampling assistance and our colleagues at the Research Center of Environmental Trace Toxic Substances, National Cheng Kung University Medical College for analytical assistance.
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Junne-Ming Sung contributed to conceptualization, methodology, validation, subjects’ recruitment; Wei-Hsiang Chang, Chung Yu Chen contributed to formal analysis, writing; Kuan-Hung Liu contributed to subjects’ recruitment, methodology; Trias Mahmudiono, Ho-Chi Hsu contributed to review, sampling and formal analysis, Wan-Ru Wang, Zhen-Yi Li contributed to data curation, visualization; Hsiu-Ling Chen contributed to conceptualization, methodology, validation, writing – original draft, editing and funding acquisition.
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Sung, JM., Chang, WH., Liu, KH. et al. The Effect of Co-Exposure to Glyphosate, Cadmium, and Arsenic on Chronic Kidney Disease. Expo Health 14, 779–789 (2022). https://doi.org/10.1007/s12403-021-00451-3
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DOI: https://doi.org/10.1007/s12403-021-00451-3