A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease

Abstract

Elevated serum-soluble urokinase receptor (suPAR) levels have been described in patients with focal segmental glomerulosclerosis (FSGS) in several different cohorts. However, it remains unclear whether this is the case for Japanese patients and whether circulating suPAR can be clinically useful as a diagnostic marker. To determine this, we measured serum suPAR levels in 69 Japanese patients with biopsy-proven glomerular diseases in a cross-sectional manner. The serum suPAR levels showed a significant inverse correlation with renal function by univariate (R(2) of 0.242) and multivariate (β=0.226) analyses. Even after excluding patients with renal dysfunction, no significant difference in the suPAR levels was detected among the groups. Receiver operating characteristic analysis and measures of the diagnostic test performance showed that suPAR was not a useful parameter for differentiating FSGS from the other glomerular diseases (AUC-ROC: 0.621), although a small subgroup analysis showed that patients with FSGS, treated with steroids and/or immunosuppressants, had significantly lower suPAR levels. Patients with ANCA-associated glomerulonephritis had significantly higher levels of suPAR compared with the other disease groups, which may be owing to their lower renal function and systemic inflammation. Thus, suPAR levels are significantly affected by renal function and have little diagnostic value even in patients with normal renal function.

Urokinase plasminogen activator receptor and its soluble form in common biopsy-proven kidney diseases and in staging of diabetic nephropathy

“…However, our results showed suPAR in type 2 DM without DN did not significantly increase as compared with healthy subjects. Some [21] and also found suPAR is inversely related to eGFR, which was consistent with our findings. The molecular weight of suPAR ranges from 20 to 50 kDa, which would pass through glomerular filtration.…”

Serum suPAR levels are modulated by immunosuppressive therapy of minimal change nephrotic syndrome

“…These findings have been confirmed in two pediatric multicenter study cohorts-the FSGS clinical trial (FSGS-CTR) and the PodoNet consortium-and in a Chinese adult cohort with FSGS [2,3], but not in a single-center pediatric study [4]. Two recent crosssectional studies in adult patients and a further large pediatric study found that suPAR levels could not discriminate FSGS from other glomerular diseases [5][6][7]. However, serum suPAR levels were inversely correlated with renal function [estimated glomerular filtration rate(eGFR)] in all three studies.…”

Biomarkers of Kidney Injury and Klotho in Patients with Atherosclerotic Renovascular Disease

“…In addition, circulating suPAR has been reported to positively associate with carotid atherosclerosis and increased cardiovascular risk in CKD (29,30), and is also reported to be involved in renal damage that might progress to CKD (31). suPAR was previously postulated to represent a specific biomarker for primary FSGS, but recently has been identified in other glomerular diseases and negatively correlated with GFR (23,30,32). In this study, the systemic level of suPAR in RVH was higher than observed in primary FSGS (approximately 4.6 ng/ml) (22,33).…”

“…The soluble urokinase plasminogen activator receptor (suPAR) circulates in the plasma, and its level correlates with atherosclerosis, cardiovascular risk, and subclinical organ damage (21). Furthermore, suPAR levels increase in CKD associated with some glomerular diseases (22,23). The degree to which levels of these ubiquitous biomarkers are altered in patients with essential hypertension (EH) or renovascular hypertension (RVH) remains unknown.…”