Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) is a Risk Indicator for eGFR Loss in Kidney Transplant Recipients

Abstract

Background suPAR is a signaling protein of the Ly6/alpha-neurotoxin family. In the kidney, suPAR contributes to podocyte foot process effacement and glomerular barrier function disruption via activating αvβ3 integrin on the podocyte membrane. Its role in allograft function or transplant-specific outcomes needs clarification. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx).Methods We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured using an uPAR ELISA assay.Results In patients who had received a living donation (LD), pre-transplant suPAR levels were significantly lower than those who had received a deceased donation (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between LD and DD recipients. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years (n = 82, p = 0.021).Conclusions After KTx, suPAR levels drop significantly. Nevertheless, suPAR-levels above 6,212 pg/ml one year after KTx are independently associated with a nearly twice as fast loss of renal function > 30% (p < 0.001). Therefore, suPAR level at one year mark might be a risk indicator of increased eGFR loss.

Association between the Serum Soluble Urokinase Plasminogen Activator Receptor and Peripheral Arterial Stiffness According to the Cardio-Ankle Vascular Index in Patients Undergoing Kidney Transplantation

“…In a broad, unselected hemodialysis cohort, a high suPAR level was a predictor of all-cause mortality (hazard ratio [HR] = 1.91, 95% CI = 1.47-2.48, p < 0.001), CV mortality (HR = 1.47, 95% CI = 1.03-2.09, p = 0.03), and non-CV mortality (HR = 1.94, 95% CI = 1.28-2.93, p = 0.002) [10]. A subsequent prospective study of 100 KT recipients demonstrated a significant decrease in suPAR levels posttransplant [11], with a strong correlation observed between suPAR levels at 1-year post-KT and eGFR loss, highlighting its potential for early detection of allograft dysfunction. However, in our study, the suPAR level negatively correlated with eGFR but lacked statistical significance.…”

“…The soluble urokinase plasminogen activator receptor (suPAR), a key player in inflammation and fibrinolysis, has emerged as a predictive marker for CVD and atherosclerosis development [7][8][9]. Previous studies have established a link between suPAR levels and chronic kidney disease (CKD), with high suPAR levels robustly predicting allcause and cardiovascular mortality in a large hemodialysis population in Italy [10,11]. In a prospective study of KT recipients, suPAR levels significantly dropped after resolving the end-stage renal disease status.…”