SummaryBackground and objectives FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children.Design, setting, participants, & measurements This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases.Results This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1-21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P.0.05). However, suPAR levels (median [25%-75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml ) versus FSGS (2487 pg/ml [2191-3351]; P,0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr .2) had lower suPAR levels than those without proteinuria (2380 pg/ml versus 3125 pg/ml , respectively; P,0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P.0.05).Conclusions On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS.