Non-classical risk factors relate to a number of alterations relevant to CKD progression and the uremic milieu, such as vascular calcification generated by the disturbed metabolism of calcium and phosphate, excess stimulation of renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction and chronic inflammation present in advanced CKD and others, that can play an important role in adverse arterial remodeling (4–6). The gene discussed is REN; the disease is chronic kidney disease.