We will review possible mechanisms of progressive renal damage, which include, but are not limited to, hemodynamic factors, the renin–angiotensin–aldosterone system (RAAS), various cytokines and growth factors, podocyte loss, dyslipidemia, proteinuria, specific mechanisms of tubulointerstitial fibrosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number. This evidence concerns the gene REN and chronic kidney disease.