TY - JOUR
T1 - Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients
AU - PROGREDIRE Working Group
AU - Torino, Claudia
AU - Pizzini, Patrizia
AU - Cutrupi, Sebastiano
AU - Postorino, Maurizio
AU - Tripepi, Giovanni
AU - Mallamaci, Francesca
AU - Reiser, Jochen
AU - Zoccali, Carmine
AU - Alati, Giovanni
AU - Barreca, Eleonora
AU - Boito, Rosalia
AU - Bovino, Margherita
AU - Bruzzese, Vincenzo
AU - Capria, Maria
AU - Cassani, Simonetta
AU - Chiarella, Salvatore
AU - Chippari, Antonio
AU - Cicchetti, Teresa
AU - Crifò-Gasparro, Edoardo
AU - Curti, Carlo
AU - D'Agostino, Francesco
AU - D'Anello, Emanuela
AU - De Gaudio, Maria
AU - Foscaldi, Aldo
AU - Fornaciari, Cesare
AU - Franco, Corrado
AU - Gaglioti, Alfredo
AU - Galati, Domenico
AU - Grandinetti, Francesco
AU - Gullo, Maurizio
AU - La Gamba, Maria Rosa
AU - Logozzo, Domenico
AU - Maimone, Iginia
AU - Mannino, Maria Letizia
AU - Mazzuca, Elena
AU - Mellace, Agazio
AU - Natale, Giuseppe
AU - Panuccio, Vincenzo
AU - Plutino, Domenico
AU - Pugliese, Antonio
AU - Reina, Anna
AU - Roberti, Rita
AU - Santangelo, Mariagrazia
AU - Sellaro, Arcangelo
AU - Scicchitano, Rosalba
AU - Vardè, Carmela
AU - Zingone, Francesco
N1 - Publisher Copyright:
© 2018 International Society of Nephrology
PY - 2018/9
Y1 - 2018/9
N2 - Introduction: The 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. Methods: We 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. Results: suPAR 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. Conclusion: In 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.
AB - Introduction: The 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. Methods: We 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. Results: suPAR 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. Conclusion: In 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.
KW - cardiovascular mortality
KW - hemodialysis
KW - mortality
KW - noncardiovascular mortality
KW - soluble urokinase plasminogen activator receptor (suPAR)
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U2 - 10.1016/j.ekir.2018.05.004
DO - 10.1016/j.ekir.2018.05.004
M3 - Article
AN - SCOPUS:85049470403
SN - 2468-0249
VL - 3
SP - 1100
EP - 1109
JO - Kidney International Reports
JF - Kidney International Reports
IS - 5
ER -