In fact, substances which accumulate over the course of advanced CKD, such as hormones (insulin, leptin, PYY3-36 produced by the colon, ghrelin) and uremic toxins (cresols, indoles, and phenols) could be responsible for the anorexia through neuroendocrine mechanisms [34] involving the melanocortin 4 receptor (MC4-R). This evidence concerns the gene MC4R and chronic kidney disease.