Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children

Abstract

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.

Is There Clinical Value in Measuring suPAR Levels in FSGS?

“…Recent findings suggest that increased levels of circulating soluble urokinase-type plasminogen activator receptor (suPAR) may trigger the podocytopathy in the majority of patients with primary FSGS. In this issue, Bock et al (2) report findings in 99 pediatric patients at a single center and conclude that serum suPAR levels are not increased in those with primary FSGS compared with children with non-FSGS glomerular disease, nonglomerular disease, or healthy controls.…”

“…The hypothesis that circulating suPAR drives the disease in a subset of FSGS is directly challenged by Bock et al (2) in this issue of CJASN. They report that suPAR levels were not significantly different in children with primary FSGS (n520), non-FSGS glomerular disease (n5240), nonglomerular CKD (n526), and healthy controls (n529).…”

A Brief Overview Of Childhood Nephrotic Syndrome: Review

“…18 Ancak daha yeni çalış-malar, suPAR'ın primer FSGS'de etken olduğuna dair kuşkulara yol açmıştır. 19,20 İMMÜNOLOJİK ANORMALLİK NS'nin immün sistemin disregülasyonu sonucu oluştuğuna dair teori en az 30 yıldır mevcuttur. Relaps sırasında hem humoral hem de hücresel immün yanıtlarda anormallik olduğuna dair pek çok rapor mevcuttur.…”

The Hype Cycle for Soluble Urokinase Receptor in FSGS

“…Most importantly, patients with eGFRs below 40 ml/min per 1.73 m 2 at baseline were excluded. This may have filtered out the significant effects of moderate to severe CKD on suPAR concentrations, thus obfuscating the observed reciprocal relationship between eGFR and suPAR concentrations seen in other studies (8,9). Also, the study population pools results from children and adults with FSGS.…”

“…First, serum suPAR concentrations could not discriminate patients with primary versus secondary FSGS or patients at risk of recurrent FSGS after kidney transplantation (5-7). Second, studies looking at determinants of serum concentrations identified kidney function to be one of the most important determinants of suPAR (8,9). This argues against the use of an absolute suPAR concentration cutoff as a biomarker for underlying FSGS.…”