Putative disease mediators include CKD-specific factors, like circulating uremic toxins and renal anemia, and CKD-unspecific factors, such as hemodynamic overload, over-activation of the sympathetic nervous system and renin–angiotensin–aldosterone system (RAAS), hypertension, endothelial dysfunction, inflammation, and increased nitro-oxidative stress [10,11]. This evidence concerns the gene REN and chronic kidney disease.