The aim of the study was to analyze systematically our observation that children with severe nephrotic syndrome (NS) have hyperphosphatemia despite normal kidney function. Forty-seven children with NS and normal glomerular filtration rate (GFR) were studied [26 with steroid-sensitive nephrotic syndrome (SSNS) and 21 with persistent NS]. The plasma phosphate level was expressed as the number of standard deviations (SDs) from the mean levels in age- and gender-matched controls. In SSNS plasma phosphate concentration was elevated (+3.7+/-2.0 SDs) during relapse and normalized (-0.7+/-1.7 SDs) in remission. In persistent NS the phosphate level was +4.0+/-2.1 SDs. Patients with marked hyperphosphatemia (>4 SDs) were younger (p<0.001), had lower plasma albumin (p<0.001), and had higher urinary protein levels (p<0.05). Hyperphosphatemia did not correlate with GFR, plasma calcium, or urinary sodium levels. Children with persistent NS had decreased serum 25(OH)D(3) and insulin-like growth factor 1 (IGF-1) concentrations. Hyperphosphatemia is prevalent among children with persistent nephrotic syndrome and normal renal function, correlates with its severity, and may result from increased urinary IGF-1 wasting.