Demystifying Chronic Kidney Disease of Unknown Etiology (CKDu): Computational Interaction Analysis of Pesticides and Metabolites with Vital Renal Enzymes

Abstract

Chronic kidney disease of unknown etiology (CKDu) has been recognized as a global non‐ communicable health issue. There are many proposed risk factors for CKDu and the exact reason is yet to be discovered. Understanding the inhibition or manipulation of vital renal enzymes by pesti‐ cides can play a key role in understanding the link between CKDu and pesticides. Even though it is very important to take metabolites into account when investigating the relationship between CKDu and pesticides, there is a lack of insight regarding the effects of pesticide metabolites towards CKDu. In this study, a computational approach was used to study the effects of pesticide metabolites on CKDu. Further, interactions of selected pesticides and their metabolites with renal enzymes were studied using molecular docking and molecular dynamics simulation studies. It was evident that some pesticides and metabolites have affinity to bind at the active site or at regulatory sites of con‐ sidered renal enzymes. Another important discovery was the potential of some metabolites to have higher binding interactions with considered renal enzymes compared to the parent pesticides. These findings raise the question of whether pesticide metabolites may be a main risk factor towards CKDu.