Soluble urokinase plasminogen activator receptor (suPAR) as a prognostic marker of mortality in healthy, general and patient populations: protocol for a systematic review and meta-analysis

Abstract

IntroductionChronic inflammation is increasingly recognised as a major contributor to disease, disability and ultimately death, but measuring the levels of chronic inflammation remains non-canonised, making it difficult to relate chronic inflammation and mortality. Soluble urokinase plasminogen activator receptor (suPAR), an emerging biomarker of chronic inflammation, has been proposed as a prognostic biomarker associated with future incidence of chronic disease and mortality in general as well as patient populations. Proper prognostic biomarkers are important as they can help improve risk stratification in clinical settings and provide guidance in treatment or lifestyle decisions as well as in the design of randomised trials. Here, we wish to summarise the evidence about the overall association of the biomarker suPAR with mortality in healthy, general and patient populations across diseases.Methods and analysisThe search will be conducted using Medline, Embase and Scopus databases from their inception to 03 June 2020 to identify studies investigating ‘suPAR’ and ‘mortality’. Observational studies and control groups from intervention studies written in English or Danish will be included. The ‘Quality In Prognosis Studies’ tool will be used to assess the risk of bias for the studies included. Unadjusted and adjusted mortality outcome measures (eg, risk ratios, ORs, HRs) with 95% CIs will be extracted for healthy individuals, general and patient populations. The primary outcome is all-cause mortality within any given follow-up. Subgroup analyses will be performed based on time of outcome, cause of death, population type, adjustments for conventional risk factors and inflammation markers.Ethics and disseminationThis systematic review will synthesise evidence on the use of suPAR as a prognostic marker for mortality. The results will be disseminated by publication in a peer-reviewed journal. Data used will be obtained from published studies, and ethics approval is therefore not necessary for this systematic review.Trial registration number PROSPEROCRD42020167401.

Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults

“…Our results from a community-based sample of Black adults are generally consistent with prior studies performed mainly in European-ancestry populations 13–18 showing higher suPAR levels are associated with female sex, increasing age, unhealthy lifestyles (smoking, sedentary behavior/obesity, alcohol intake), psychosocial factors, CVD risk factors (eg, diabetes, hypertension, and dyslipidemia), and lower eGFR. In JHS, demographic, behavioral, and clinical factors accounted for ≈29% of the suPAR phenotypic variance.…”

“…8 Therefore, suPAR has been suggested as a useful prognostic biomarker of chronic inflammation and immune activation across a range of clinical settings. 13 Several prior cross-sectional and longitudinal studies have implicated suPAR as a biomarker for atherosclerosis, clinical CVD events, and mortality in patients with preexisting diseases [14][15][16][17][18][19][20][21] or individuals from the general population. [22][23][24][25][26] The associations of higher suPAR with prevalent subclinical vascular disease measures (left ventricular hypertrophy, left ventricular mass index, and aortic artery calcification) and incident coronary heart disease, HF, stroke, and mortality in JHS following adjustment for CVD risk factors are consistent with prior studies and provide support for suPAR as a CVD biomarker in Blacks, independent of both eGFR and CRP.…”

Soluble Urokinase Plasminogen Activator Receptor as a Decision Marker for Early Discharge of Patients with COVID-19 Symptoms in the Emergency Department

“…Elevated suPAR is found in a wide range of diseases both, acute, chronic, non-communicable, and infectious. [ 9 , 10 ] Soluble urokinase plasminogen activator receptor has been investigated in several viral infections, including Human Immunodeficiency Virus (HIV), hepatitis B and C, Crimean-Congo hemorrhagic fever, and hantavirus. In all cases, elevated suPAR associates with clinical severity and mortality.…”

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction

“…This has been reported consistently in studies showing that increased suPAR is associated with systemic inflammation and adverse prognosis in patients with infectious diseases [ 18 , 19 ]. Elevated suPAR levels are implicated in different disease settings associated with inflammation including cardiovascular disease, diabetes, rheumatic disease and cancer, whereas suPAR levels may even be predictable of mortality in the general population [ 20 , 21 , 22 ]. Furthermore, both myeloma cells and myeloid cells residing in the myeloma compartment of the bone marrow niche express uPAR and may contribute to the increased suPAR levels detected in the serum of patients with MM [ 23 , 24 , 25 ].…”