These complications are attributed to hyperfiltration in the remnant glomeruli following renal parenchymal loss, which leads to the development of glomerulosclerosis, activation of the renin–angiotensin system, and a gradual deterioration of renal function [68, 69] Studies have indicated that the mesangial alterations occur early in the course of reflux nephropathy, even before proteinuria is detectable by routine analysis; the other extreme is the occurrence of focal segmental glomerulosclerosis (FSGS) with clinically significant proteinuria and nephrotic syndrome [70]. The gene discussed is REN; the disease is focal segmental glomerulosclerosis.