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Environment/Climate Change

Atrazine use and markers of kidney function and nephrotoxicity among male farmers in the Biomarkers of Exposure and Effect in Agriculture Study Gabriella Andreotti* Gabriella Andreotti Joseph J Shearer Dale P Sandler Anna M Lukkari Richard Remigio Christine G Parks Vicky C Chang Venkata Sabbisetti Laura E Beane Freeman Amy Karger Jonathan N Hofmann

Background: Atrazine is a widely used herbicide that has been associated with malignant and non-malignant kidney disease and reduced kidney function in the Agricultural Health Study (AHS). However, little is known about the association between atrazine use and specific kidney disease biomarkers. Objective: We evaluated the associations between atrazine use and clinical biomarkers of kidney function and nephrotoxicity among male farmers in the Biomarkers of Exposure and Effect in Agriculture study, a sub-cohort of the AHS. Methods: We included 264 farmers with: 1) recent atrazine use (use within the last 3 months), nearly all of whom also had past use; 2) former atrazine use (top tertile of lifetime use but no recent use); and 3) no/low atrazine use (no recent use and no or low lifetime use). These groups (n=88 each) were frequency-matched on age and state of residence (Iowa, North Carolina). Markers were measured in serum (creatinine, cystatin C, urea nitrogen, uric acid) and urine (kidney injury molecule-1, albumin, creatinine). The 2021 CKD-EPI creatinine-cystatin C equation was used to calculate estimated glomerular filtration rate (eGFRcr-cys). The percent difference in these markers across groups of atrazine use was estimated using multivariable linear regression. Results: Recent atrazine users had lower eGFRcr-cys (-6.7%; 95%CI: -11.7%, -1.4%) and higher levels of serum creatinine (7.0%; 95%CI: 1.4%, 12.8%), cystatin C (7.4%; 95%CI: 1.2%, 13.9%), and uric acid (6.1%; 95%CI: -0.4%, 13%) compared to farmers with no/low atrazine use. Comparisons between farmers with former atrazine use and no/low use were null, except for an inverse association with blood urea nitrogen (-6.9%; 95%CI: -12.9%, -5.0%).  Conclusions: Our findings add to the evidence that atrazine use, particularly among recent users, is associated with diminished kidney function.  Additional studies are needed to clarify the mechanisms through which atrazine may contribute to kidney damage.