Increased Serum Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in FSGS: A Meta-Analysis

Abstract

Introduction. The soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS. Methods. Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Results. A total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants=814; studies=9, I2=85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference. Conclusions. Our meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.

MicroRNAs as Biomarkers for Nephrotic Syndrome

“…Indeed, it is reported that the overexpression of uPAR in podocytes as well as the administration of suPAR in mice caused proteinuria [ 57 ]. Increased suPAR levels in FSGS patients were also reported in meta-analysis reports [ 58 , 59 ]. However, several conflicting results have also been reported [ 60 , 61 , 62 ]; thus, it is still controversial whether suPAR is involved in the pathogenesis of FSGS.…”

Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method

“…The usefulness of suPAR as a biomarker is promising, but still a matter of debate due to ambiguous results in previous studies which have shown that suPAR levels depended on the degree of renal insufficiency, did not correlate with the extent of proteinuria and were also increased in other kidney diseases than FSGS 27–30 . Furthermore, the role of suPAR in progression of FSGS and chronic kidney disease is discussed in the scientific community 1,31,32 . Varying results in former investigations might partly arise from application of different ELISA kits using differing reagents and antibodies.…”

Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis

“…High-quality meta-analysis has been increasingly regarded a key tool for achieving evidence 12 13. In a previous meta-analysis,14 it was shown that the concentration of suPAR was higher in patients with FSGS when compared with normal subjects; however, the heterogeneity was greater, and due to the small number of included studies no subgroup analysis was performed. Our meta-analysis included higher number of studies, a subgroup analysis, and sensitivity and specificity analyses for the diagnosis of the FSGS threshold using the concentration of suPAR.…”