Evaluation of serum soluble urokinase plasminogen activator receptor as a marker for steroid-responsiveness in children with primary nephrotic syndrome

Abstract

Nephrotic syndrome (NS) is the most common primary glomerular disease among children. It runs a relapsing course involving prolonged periods of treatment with corticosteroids and other immunosuppressive medications. Soluble urokinase plasminogen activator receptor (suPAR) has been regarded as an inflammatory as well as a permeability factor. The aim of our study was to evaluate serum suPAR levels in children with NS and its relation to steroid responsiveness. Our study was carried out on 75 children who were already diagnosed as having NS; they were classified into three groups (steroid sensitive, steroid dependent, and steroid resistant). Furthermore, 40 apparently healthy children, age and sex matched with the NS patients, were enrolled as controls. All children had undergone assessment of serum suPAR, renal function tests (urea and creatinine), serum albumin, C-reactive protein, and 24-h protein in urine. The study found that suPAR level was significantly different between the studied groups (P <0.05), being highest in steroid-resistant NS (66.52 ± 9.7 ng/mL), followed by steroid dependent (56.82 ± 11.09 ng/mL), and steroid-sensitive patients (26.22 ± 3.86 ng/mL), and lowest in the control group (20.29 ± 0.69 ng/mL). When receiver operating characteristics curves were plotted, suPAR had high sensitivities and specificities in predicting steroid responsiveness, [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.911-1.000, P <0.001], steroid dependence (AUC = 1.00, 95% CI = 0.929-1.000, P <0.001), and predicting steroid resistance. Our study indicates that suPAR is significantly higher in children with primary NS and varies according to their response to steroid therapy. It may act as a marker for steroid responsiveness in these children.

The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

“…This finding is in contrast with Peng et al (28) results, reporting that su-PAR level was different between SRNS and SSNS groups. Furthermore, Peng and Mousa et al also found that supAR was significantly higher in SRNS patients compared to the SSNS, SDNS, and normal population (23). stated that suPAR levels are specifically associated with primary FSGS, and chronic overexpression of suPAR leads to an FSGS-like nephropathy in mice, and treatment with mycophenolate mofetil was associated with a lower serum su-PAR level (26,60).…”

“…However, just recently, the usefulness of the soluble urokinase plasminogen activator receptor as a biomarker in clinically estimating and differentiating SRNS was corroborated (14,15,(20)(21)(22)(23)(24)(25)(26)(27). Some studies also reported that using suPAR level, it is possible to distinguish whether FSGS patients are responsive or resistant to therapy (23,28). Wei et al (26) stated that the serum concentrations of this receptor are significantly elevated in patients with FSGS compared to healthy subjects and in pre-transplant patients who later develop the recurrent form of this syndrome after transplantation (26,29).…”

“…Furthermore, some studies reported the usefulness of suPAR in identifying podocytopathy-related inflammation (30). In contrast, Peng et al demonstrated that the receptor's level helped to differentiate between SRNS and SSNS (23,28). Therefore, changes in total suPAR are useful as biomarkers of glomerular disease activity (26).…”

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

“…(2) Soluble urokinasetype plasminogen activator recep tor (suPAR) suPAR was once postulated to be the circulating permea bility factor in FSGS or SRNS 65) , but it was soon refuted by several studies 66,67) . Regarding predictive markers of steroid responsiveness in children with NS, two studies were found 68,69) . While individual studies reported the significance of this molecule in distinguishing SRNS from SSNS, meta analysis of these two studies was not significant (Fig.…”

Urinary CD80 and Serum Soluble Urokinase Plasminogen Activator Receptor (SuPAR) as Novel Diagnostic Biomarkers in Pediatric Patients with Nephrotic Syndrome

“…Serum soluble urokinase-type plasminogen activator receptor (SuPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein on the cell membrane secreted during infections and inflammation [15]. SuPAR is expressed in various cell types such as machrophages, monocytes, endothelial cells, neutrophil, certain cancer cells and kidney podocytes [16].…”