Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis

作者：Huang, Jing; Liu, Gang; Zhang, Yi-miao; Cui, Zhao; Wang, Fang; Liu, Xiao-Jing; Chu, Rong; Zhao, Ming-hui^*

来源：BMC Medicine, 2014, 12(1): 81.

DOI：10.1186/1741-7015-12-81

• Focal segmental glomerulosclerosis
• Urinary soluble urokinase receptor
• Podocyte

Background: Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. Recent studies have proposed that plasma soluble urokinase receptor (suPAR) might be a causative circulating factor but this proposal has caused controversy. This study aimed to measure urinary suPAR levels in patients with primary FSGS and its significance in the pathogenesis of FSGS. @@@ Methods: Sixty-two patients with primary FSGS, diagnosed between January 2006 and January 2012, with complete clinical and pathologic data were enrolled, together with disease and normal controls. Urinary suPAR levels were measured using commercial ELISA kits and were corrected by urinary creatinine (Cr). The associations between urinary suPAR levels and clinical data at presentation and during follow up were analyzed. Conditionally immortalized human podocytes were used to study the effect of urinary suPAR on activating beta 3 integrin detected by AP5 staining. @@@ Results: The urinary suPAR level of patients with primary FSGS (500.56, IQR 262.78 to 1,059.44 pg/mu mol Cr) was significantly higher than that of patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/mu mol Cr, P = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/mu mol Cr, P < 0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/mu mol Cr, P < 0.001) and normal subjects (183.59, IQR 103.92 to 228.78 pg/mu mol Cr, P < 0.001). The urinary suPAR level of patients with cellular variant was significantly higher than that of patients with tip variant. The urinary suPAR level in the patients with primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P = 0.024). During follow up, the urinary suPAR level of patients with complete remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/mu mol Cr versus 217.68, IQR 121.77 to 415.55 pg/mu mol Cr, P = 0.017). The AP5 signal was strongly induced along the cell membrane when human differentiated podocytes were incubated with the urine of patients with FSGS at presentation, and the signal could be reduced by a blocking antibody specific to uPAR. @@@ Conclusions: Urinary suPAR was specifically elevated in patients with primary FSGS and was associated with disease severity. The elevated urinary suPAR could activate beta 3 integrin on human podocytes.

• 出版日期2014-5-20
• 单位北京大学