Renal dysfunction is known to lead to accumulation of CKD toxins such as indoxyl sulfate, kynurenic acid, indole-3-acetic acid, p-cresol sulfate which have been shown to directly inhibit mitochondrial oxidative phosphorylation, cause metabolic perturbation and insulin resistance in peripheral tissues28,34,35 (Fig. 8). This evidence concerns the gene INS and chronic kidney disease.