Low birth weight (LBW) is associated with reduced nephron endowment. Clinical-pathologic features of post adaptive focal segmental glomerulosclerosis (FSGS) have been observed in subjects with prematurity and very LBW. We aimed to investigate the correlation between LBW and outcome in a cohort of 89 children with idiopathic nephrotic syndrome (NS) (2-12 years-old at onset, followed for > 3years), of whom 21 with LBW (birth weight < 10th percentile for gestational age, gender, ethnicity, and maternal parity or birth weight < 2500g). Children with NS and LBW were found to have FSGS more frequently than children with normal birth weight (NBW) [8/21 = 38% vs. 4/68 = 6%; odds ratio, OR 7.754 (95% confidence interval, CI 2.184-27.525); χ2 = 9.817; p < 0.003]. Children with LBW and cortico-sensitive NS had a greater risk of cortico-dependence (CD) than those with NBW [10/13 = 76.9% vs. 28/63 = 44.4%, OR 4.744 (1.188-18.936); χ2 = 4.158; p < 0.05]. Moreover, children with LBW and CDNS needed a greater dose of immunosuppressive drugs than those with NBW [OR 4 (1.153-13.877); χ2 = 3.842; p = 0.05]. LBW children developing NS had higher risk of FSGS and CD, and needed heavier immunosuppressive therapy than those with NBW. These data might suggest a conditioning role for hemodynamic and podocyte changes due to reduced nephron mass in LBW.