Investigating a link between Glyphosate and Chronic Kidney Disease of Unknown Origin (CKDu) through Glyphosate’s interactions with Renal Proteins in Molecular Docking

Chronic Kidney Disease of unknown origin (CKDu) is a subtype of chronic kidney disease that is mainly observed in agricultural communities in Sri Lanka, India, and parts of Central America. The cases of CKDu in agricultural settings are correlated with the use of pesticides. Among these, glyphosate, an herbicide, has been shown to correlate with CKDu cases in Sri Lanka. Various mechanisms have been proposed for glyphosate’s association with CKDu including the inhibition of CYP450 enzymes and the disruption of the renin-angiotensin- aldosterone system. Given that glyphosate’s mode of action involves the binding to and inhibition of the protein EPSP synthase, this study employs molecular docking to identify renal protein candidates with favorable binding interactions with glyphosate at an atomic level. The results revealed that renal proteins such as interleukin-6, uromodulin, and prorenin exhibited energetically favorable binding with glyphosate, potentially influencing the prognosis of CKDu. In the future, it is necessary to experimentally validate these findings through in-vitro studies to confirm glyphosate’s binding with these proteins of interest. The experimental validation could perhaps lend insights into the etiology of the CKDu.