Nephrogenesis is a complex process of nephron formation and maturation that can be compromised by preterm delivery and intrauterine growth restriction. This study aimed to evaluate and compare urinary Cys-C levels with renal volume in a cohort of preterm and term twins, adequate for gestational age or intrauterine growth restricted, to investigate their values in different conditions of nephrogenesis.The study was performed on twins at 30-40 days of postnatal corrected age: renal volumes were measured by 3D ultrasound technology and urine samples were analyzed for Cystatin-C. A follow-up was performed by Cystatin-C.Renal volumes in preterm and intrauterine growth-restricted twins showed values significantly lower than those observed in term twins and were inversely correlated to urinary Cystatin-C levels. During the follow-up, intrauterine growth-restricted twins showed amplified levels of urinary Cystatin-C; in contrast, invariable or decreased levels were observed in adequate for gestational age twins.Urinary Cystatin-C, evaluated when intrauterine/extrauterine nephrogenesis could be considered completed, concurrently with renal volume assessment can improve the identification of neonates with initial kidney impairment. Its potential value as a useful marker in monitoring physiological/pathological renal conditions could be considered, mainly for neonates at elevated risk of developing long-term renal diseases.Urinary Cys-C levels are inversely correlated to renal volumes and reflect nephrogenesis conditions.No data in literature are reported regarding: (a) the concurrent assessment of renal volumes and urinary levels of Cystatin-C in preterm and term twins with different conditions of gestational life, i.e., AGA and IUGR and (b) the follow-up of IUGR and preterm neonates using the urinary Cys-C determination.The variations of urinary Cys-C levels, observed in the follow-up of preterm and/or IUGR neonates, support the usefulness of monitoring those neonates with altered nephrogenesis, who are later at risk for renal impairment and for long-term renal diseases.