Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients

Abstract

IntroductionThe soluble receptor of urokinase plasminogen activator (suPAR) is an innate immunity/inflammation biomarker predicting cardiovascular (CV) and non-CV events in various conditions, including type 2 diabetic patients on dialysis. However, the relationship between suPAR and clinical outcomes in the hemodialysis population at large has not been tested.MethodsWe measured plasma suPAR levels (R&D enzyme-linked immunosorbent assay [ELISA]) in 1038 hemodialysis patients with a follow-up of 2.9 years (interquartile range = 1.7−4.2) who were enrolled in the PROGREDIRE study, a cohort study involving 35 dialysis units in 2 regions in Southern Italy.ResultssuPAR was strongly (P < 0.001) and independently related to female gender (β = −0.160), age (β = 0.216), dialysis vintage (β = 0.264), CV comorbidities (β = 0.105), alkaline phosphatase (β = 0.136), albumin (β = −0.147), and body mass index (BMI; β = 0.174) (all P < 0.006). In fully adjusted analyses, suPAR tertiles predicted the risk of all-cause mortality (third tertile vs. first tertile hazard ratio (HR) = 1.91, 95% confidence interval (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); these relationships were not modified by diabetes or other risk factors. suPAR added only modest prognostic risk discrimination and reclassification power for these outcomes to parsimonious models based on simple clinical variables.ConclusionIn conclusion, suPAR robustly predicted all-cause and both CV and non-CV mortality in a large unselected hemodialysis population. Intervention studies are needed to definitively test the hypothesis that suPAR is causally implicated in clinical outcomes in this population.

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

“…In our data, dialysis vintage was signi cantly correlated to suPAR levels prior to transplantation (p = 0.013, r = 0.258). In congruence, among other factors, dialysis vintage as well as the age of the patient have recently been linked to the suPAR levels in dialysis patients [11], [12]. After KTx, the suPAR levels decreased to a comparable level at the one-year mark (Fig.…”

“…Similarly, morbidity and mortality of DD recipients are usually higher that is perhaps related to longer dialysis vintage [23], [24]. Notably, Torino and Drechsler et al demonstrated that higher suPAR levels even translated into all-cause and both CVD and non-CVD mortality in hemodialysis patients [11], [12].…”

Serum soluble urokinase plasminogen activator receptor in adolescents: interaction of chronic pain and obesity

“… 17 , 24 , 26 , 32 , 33 , 45 Furthermore, it is considered a marker and may be a predictor of outcomes in a variety of cardiovascular diseases associated with inflammation. 1 , 14 , 17 , 22 , 32 , 41 , 47 , 54 …”

“…Serum suPAR was measured by enzyme immunoassay from R&D Systems (DUP00; Minneapolis, MN) as described previously. 54 The samples were diluted 5-fold before assay and assayed in duplicate. The sensitivity of the assay without dilution of the serum is <33 pg/mL, which translates to <0.2 ng/mL with the 5-fold dilution of serum.…”

“…Overweight and obesity, both of which have also been associated with inflammation, may have increased serum suPAR. 26 , 32 , 33 , 45 , 54 We are aware of 2 studies evaluating suPAR in children with obesity that showed conflicting results. 4 , 29 We are not aware of systematic studies of the independent effect of chronic pain on suPAR dynamics.…”