Soluble urokinase-type plasminogen activator receptor and incident end-stage renal disease in Chinese patients with chronic kidney disease

Background: Soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, was shown to be associated with outcomes and kidney disease among various patient populations. The prognostic role of circulating suPAR levels in patients with chronic kidney disease (CKD) needs to be investigated in a cohort with large sample size of renal diseases. Methods: We measured serum suPAR concentration in 2391 CKD patients in the multicenter Chinese Cohort Study of Chronic Kidney Disease, and investigated the association of serum suPAR with the prespecified endpoint event, end-stage renal disease (ESRD), using Cox proportional hazards regression model. Results: Altogether, 407 ESRD events occurred during the median follow-up of 54.8 (interquartile range: 47.5-62.2) months. The higher levels of serum suPAR were independently associated with increased risk of incident ESRD after adjusting for potential confounders including the baseline estimated glomerular filtration rate categories, with the hazard ratios (HRs) of 1.53 [95% confidence intervals (CIs) 1.10-2.12] for the top tertile (≥3904 pg/mL) compared with the bottom tertile (<2532 pg/mL). When stratified by the etiologies of CKD, among patients with glomerulonephritis (GN), serum suPAR levels were also independently associated with the higher risk of ESRD, with an HR of 1.61 (95% CI 1.03-2.53) in the top tertile compared with the bottom tertile. Conclusions: Circulating suPAR level was independently associated with an increased risk of progression to ESRD in Chinese CKD patients, especially in those with an etiology of GN.