We investigated whether losartan (L, angiotensin II type-1 receptor blocker) alone or combined with synthetic (tempol, T) or natural antioxidants (olive leaf extract, O) could alter Klotho/Wnt4/β-catenin signaling, thus reducing fibrosis and slowing the progression of focal segmental glomerulosclerosis (FSGS) in spontaneously hypertensive rats (SHR). This evidence concerns the gene AGTR1 and focal segmental glomerulosclerosis.