Abstract
IntroductionIdentifying patients at high risk of developing kidney disease could lead to early clinical interventions that prevent or slow disease progression. Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker thought to be involved in the pathogenesis and development of kidney disease. We aimed to determine whether elevated plasma suPAR measured at hospital admission is associated with incident kidney disease in patients presenting to the emergency department.Materials and MethodsThis was a retrospective registry-based cohort study performed at the Emergency Department of Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. Patients were included in the study from November 2013 to March 2017 and followed until June 2017. Patients were excluded if they were diagnosed with kidney disease or died prior to index discharge. Plasma suPAR was measured at hospital admission, and the main outcome was time to incident kidney disease, defined by ICD-10 diagnosis codes for both chronic and acute kidney conditions. Association between suPAR and time to incident kidney disease was assessed by Cox proportional hazard regression analysis.ResultsIn total, 25,497 patients (median age 58.1 years; 52.5% female) were admitted to the emergency department and followed for development of kidney disease. In multivariable Cox regression analysis adjusting for age, sex, eGFR, CRP, cardiovascular disease, hypertension, and diabetes, each doubling in suPAR at hospital admission was associated with a hazard ratio of 1.57 (95% CI: 1.38–1.78, P < 0.001) for developing a chronic kidney condition and 2.51 (95% CI: 2.09–3.01, P < 0.001) for developing an acute kidney condition.DiscussionIn a large cohort of acutely hospitalized medical patients, elevated suPAR was independently associated with incident chronic and acute kidney conditions. This highlights the potential for using suPAR in risk classification models to identify high-risk patients who could benefit from early clinical interventions. The main limitation of this study is its reliance on accurate reporting of ICD-10 codes for kidney disease.
Highlights
Identifying patients at high risk of developing kidney disease could lead to early clinical interventions that prevent or slow disease progression
Compared with patients excluded due to prior kidney disease (n = 2,836), the study cohort had higher median estimated glomerular filtration rate (eGFR) (88.7 vs. 56.7 mL/min/1.73 m2), lower median C-reactive protein (CRP) (4.0 vs. 16.0 mg/L), and lower median Soluble urokinase plasminogen activator receptor (suPAR) (2.7 vs. 4.5 ng/mL)
Compared with patients excluded for any reason (n = 3,591), the study cohort had higher median eGFR (88.7 vs. 57.4 mL/min/1.73 m2), lower median CRP (4.0 vs. 26.0 mg/L), and lower median suPAR (2.7 vs. 4.9 ng/mL)
Summary
Identifying patients at high risk of developing kidney disease could lead to early clinical interventions that prevent or slow disease progression. Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker thought to be involved in the pathogenesis and development of kidney disease. We aimed to determine whether elevated plasma suPAR measured at hospital admission is associated with incident kidney disease in patients presenting to the emergency department. Identifying patients at high risk of developing CKD may lead to earlier medical interventions that reduce morbidity and mortality associated with disease progression (James et al, 2010; Akbari et al, 2014). Soluble urokinase plasminogen activator receptor (suPAR) is an endogenous signaling molecule and biomarker of chronic inflammation, and elevated suPAR levels have been associated with a range of diseases and mortality (Eugen-Olsen et al, 2010). There is growing evidence that suPAR may reflect the pathogenesis of kidney disease, and it has been proposed that suPAR itself causes kidney disease by damaging renal podocytes (Wei et al, 2011; Hayek et al, 2017)
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