Original Manuscript
Procalcitonin as an Early Predictor of Contrast-Induced Acute Kidney Injury in Patients With Acute Coronary Syndromes Who Underwent Percutaneous Coronary Intervention
Angiology 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715572218 ang.sagepub.com
Alparslan Kurtul, MD1, Sani Namik Murat, MD1, Mikail Yarlioglues, MD1, Mustafa Duran, MD1, Adil Hakan Ocek, MD1, Ibrahim Etem Celik, MD1, Alparslan Kilic, MD1, Cemal Koseoglu, MD1, Fatih Oksuz, MD1, and Veysel Ozgur Baris, MD2
Abstract Contrast-induced acute kidney injury (CI-AKI) is a major issue after percutaneous coronary intervention (PCI), especially in the setting of acute coronary syndrome (ACS). Contrast-induced acute kidney injury is associated with increased mortality and morbidity. Inflammation plays an important role in the pathophysiology of CI-AKI. Procalcitonin (PCT) is introduced as a new marker of inflammation. We sought to examine whether admission PCT levels predict the development of CI-AKI. Patients (n ¼ 814) were divided into 2 groups, namely, CI-AKI () and CI-AKI (þ). An increase in serum creatinine of 0.5 mg/dL from baseline within 48 to 72 hours of contrast exposure was defined as CI-AKI. Contrast-induced acute kidney injury occurred in 96 (11.8%) patients. The PCT levels were significantly higher in patients with CI-AKI than in those without, 0.11 (0.056-0.495) vs 0.04 (0.020.078) mg/L; P < .001. After multivariable analysis, PCT remained a significant independent predictor of CI-AKI (odds ratio 2.544; 95% CI [1.207-5.347]; P ¼ .014) as well as age, women, white blood cell, hemoglobin, glomerular filtration rate, creatine kinase myocarial band, and SYNTAX score. In conclusion, serum PCT levels are independently associated with a risk of CI-AKI in patients with ACS who underwent urgent PCI. Keywords procalcitonin, contrast-induced acute kidney injury, percutaneous coronary intervention, acute coronary syndrome
Introduction Contrast-induced acute kidney injury (CI-AKI) is one of the most serious complications of percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury occurs more frequently after unplanned coronary interventions,1-3 and the development of CI-AKI is one of major determinants of short- and long-term morbidity and mortality after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), despite successful early coronary revascularization.4-9 Although the pathogenesis of CI-AKI is not completely understood, multiple mechanisms may be involved, and inflammation plays a role. Contrast-induced acute kidney injury is associated with the production
of proinflammatory cytokines and chemokines within the kidney.10-13 Procalcitonin (PCT) has been described as a novel marker of systemic inflammatory states. In response to proinflammatory stimuli, especially bacterial infections, PCT is increased by
1
Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey 2 Department of Cardiology, Ankara University Faculty of Medicine, Ankara, Turkey Corresponding Author: Alparslan Kurtul, Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 3, 2015
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Angiology
release from all parenchymal tissues and differentiated cell types throughout the body.14,15 Several studies have shown that PCT levels were increased in patients with ACS on admission,16 but other investigations have demonstrated that serum PCT concentrations are in the normal range in patients with uncomplicated STEMI.17,18 Numerous studies have reported that elevated PCT levels were associated with a worse prognosis in the setting of ACS.19-21 To the best of our knowledge, no study examined the relationship between value of PCT as a biomarker of inflammation and development of CI-AKI in the setting of ACS. The aim of this study was to investigate the association between serum PCT levels and the risk of subsequent CI-AKI in patients with ACS after unplanned PCI.
Methods Patients and Study Design Between March 2012 and August 2014, a total of 840 consecutive patients with acute STEMI or NSTE-ACS undergoing urgent PCI were enrolled. The patients were suitable for inclusion if they had been admitted within 12 hours of the onset of chest pain that had lasted for 30 minutes with ST-segment elevation of >0.2 mV in 2 contiguous leads and elevation of cardiac troponin level greater than the upper limit of normal. Patients were also enrolled if they had an episode of ischemic chest pain of 10 minutes with transient or persistent ST-segment depression, T-wave inversion, and/or elevation in cardiac troponin level greater than the upper limit of normal, thus presenting with refractory angina or hemodynamic instability, despite optimal drug therapy within 24 hours of admission. We excluded patients receiving hemodialysis or administration of metformin and nonsteroidal anti-inflammatory drugs. We also excluded patients if they had contrast exposure 2 weeks before PCI, died during PCI, or if they refused further treatment or were discharged for various reasons. To avoid other variables that influence the serum levels of PCT, we also excluded patients with a history of recent surgery or trauma within the previous month, known malignancies, febrile conditions, autoimmune disorder, acute or chronic inflammatory disease at study entry, or history of recent infection. Patients were also excluded if fever (body temperature > 37.5 C) was observed in the emergency department or coronary care unit. Finally, 814 patients were included in our analysis. The patients were divided into 2 groups, namely, CI-AKI () and CI-AKI (þ).
Definitions Hypertension was defined as a blood pressure >140/90 mm Hg based on at least 2 measurements or the use of antihypertensive drugs. Diabetes mellitus was defined as a fasting blood glucose >126 mg/dL based on at least 2 measurements or the use of antidiabetic agents. Hypercholesterolemia was defined as a baseline cholesterol level of
>200 mg/dL and/or a low-density lipoprotein cholesterol level of >130 mg/dL or previously diagnosed and treated hypercholesterolemia. Current smokers were those smoking regularly in the previous 6 months. Family history of coronary artery disease was defined as a coronary event occurring before 55 and 65 years, for first-degree male and female relatives, respectively. Contrast-induced acute kidney injury was defined as an increase in serum creatinine level of 25% or 0.5 mg/dL above the baseline value which occurs within 48 to 72 hours after the procedure.22
Laboratory Data Blood samples were obtained and assessed at the time of admission. Baseline creatinine concentrations, baseline estimated glomerular filtration rate (eGFR), white blood cell count, platelet count, and hemoglobin levels were measured. The eGFR was calculated using the Modification of Diet in Renal Disease study equation.23 Serum creatinine levels were measured daily postprocedure for at least 48 to 72 hours. The level of PCT was determined within 30 minutes using VIDAS BRAHMS PCT assay (BioMerieux Clinical Diagnostics., France), which is an enzyme-linked fluorescent immunoassay, performed in an automated VIDAS instrument (BioMerieux Inc, Marcy l’Etoile, France). The normal reference limit was accepted as
Procalcitonin as an Early Predictor of Contrast-Induced Acute Kidney Injury in Patients With Acute Coronary Syndromes Who Underwent Percutaneous Coronary Intervention
Angiology 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715572218 ang.sagepub.com
Alparslan Kurtul, MD1, Sani Namik Murat, MD1, Mikail Yarlioglues, MD1, Mustafa Duran, MD1, Adil Hakan Ocek, MD1, Ibrahim Etem Celik, MD1, Alparslan Kilic, MD1, Cemal Koseoglu, MD1, Fatih Oksuz, MD1, and Veysel Ozgur Baris, MD2
Abstract Contrast-induced acute kidney injury (CI-AKI) is a major issue after percutaneous coronary intervention (PCI), especially in the setting of acute coronary syndrome (ACS). Contrast-induced acute kidney injury is associated with increased mortality and morbidity. Inflammation plays an important role in the pathophysiology of CI-AKI. Procalcitonin (PCT) is introduced as a new marker of inflammation. We sought to examine whether admission PCT levels predict the development of CI-AKI. Patients (n ¼ 814) were divided into 2 groups, namely, CI-AKI () and CI-AKI (þ). An increase in serum creatinine of 0.5 mg/dL from baseline within 48 to 72 hours of contrast exposure was defined as CI-AKI. Contrast-induced acute kidney injury occurred in 96 (11.8%) patients. The PCT levels were significantly higher in patients with CI-AKI than in those without, 0.11 (0.056-0.495) vs 0.04 (0.020.078) mg/L; P < .001. After multivariable analysis, PCT remained a significant independent predictor of CI-AKI (odds ratio 2.544; 95% CI [1.207-5.347]; P ¼ .014) as well as age, women, white blood cell, hemoglobin, glomerular filtration rate, creatine kinase myocarial band, and SYNTAX score. In conclusion, serum PCT levels are independently associated with a risk of CI-AKI in patients with ACS who underwent urgent PCI. Keywords procalcitonin, contrast-induced acute kidney injury, percutaneous coronary intervention, acute coronary syndrome
Introduction Contrast-induced acute kidney injury (CI-AKI) is one of the most serious complications of percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury occurs more frequently after unplanned coronary interventions,1-3 and the development of CI-AKI is one of major determinants of short- and long-term morbidity and mortality after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), despite successful early coronary revascularization.4-9 Although the pathogenesis of CI-AKI is not completely understood, multiple mechanisms may be involved, and inflammation plays a role. Contrast-induced acute kidney injury is associated with the production
of proinflammatory cytokines and chemokines within the kidney.10-13 Procalcitonin (PCT) has been described as a novel marker of systemic inflammatory states. In response to proinflammatory stimuli, especially bacterial infections, PCT is increased by
1
Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey 2 Department of Cardiology, Ankara University Faculty of Medicine, Ankara, Turkey Corresponding Author: Alparslan Kurtul, Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 3, 2015
2
Angiology
release from all parenchymal tissues and differentiated cell types throughout the body.14,15 Several studies have shown that PCT levels were increased in patients with ACS on admission,16 but other investigations have demonstrated that serum PCT concentrations are in the normal range in patients with uncomplicated STEMI.17,18 Numerous studies have reported that elevated PCT levels were associated with a worse prognosis in the setting of ACS.19-21 To the best of our knowledge, no study examined the relationship between value of PCT as a biomarker of inflammation and development of CI-AKI in the setting of ACS. The aim of this study was to investigate the association between serum PCT levels and the risk of subsequent CI-AKI in patients with ACS after unplanned PCI.
Methods Patients and Study Design Between March 2012 and August 2014, a total of 840 consecutive patients with acute STEMI or NSTE-ACS undergoing urgent PCI were enrolled. The patients were suitable for inclusion if they had been admitted within 12 hours of the onset of chest pain that had lasted for 30 minutes with ST-segment elevation of >0.2 mV in 2 contiguous leads and elevation of cardiac troponin level greater than the upper limit of normal. Patients were also enrolled if they had an episode of ischemic chest pain of 10 minutes with transient or persistent ST-segment depression, T-wave inversion, and/or elevation in cardiac troponin level greater than the upper limit of normal, thus presenting with refractory angina or hemodynamic instability, despite optimal drug therapy within 24 hours of admission. We excluded patients receiving hemodialysis or administration of metformin and nonsteroidal anti-inflammatory drugs. We also excluded patients if they had contrast exposure 2 weeks before PCI, died during PCI, or if they refused further treatment or were discharged for various reasons. To avoid other variables that influence the serum levels of PCT, we also excluded patients with a history of recent surgery or trauma within the previous month, known malignancies, febrile conditions, autoimmune disorder, acute or chronic inflammatory disease at study entry, or history of recent infection. Patients were also excluded if fever (body temperature > 37.5 C) was observed in the emergency department or coronary care unit. Finally, 814 patients were included in our analysis. The patients were divided into 2 groups, namely, CI-AKI () and CI-AKI (þ).
Definitions Hypertension was defined as a blood pressure >140/90 mm Hg based on at least 2 measurements or the use of antihypertensive drugs. Diabetes mellitus was defined as a fasting blood glucose >126 mg/dL based on at least 2 measurements or the use of antidiabetic agents. Hypercholesterolemia was defined as a baseline cholesterol level of
>200 mg/dL and/or a low-density lipoprotein cholesterol level of >130 mg/dL or previously diagnosed and treated hypercholesterolemia. Current smokers were those smoking regularly in the previous 6 months. Family history of coronary artery disease was defined as a coronary event occurring before 55 and 65 years, for first-degree male and female relatives, respectively. Contrast-induced acute kidney injury was defined as an increase in serum creatinine level of 25% or 0.5 mg/dL above the baseline value which occurs within 48 to 72 hours after the procedure.22
Laboratory Data Blood samples were obtained and assessed at the time of admission. Baseline creatinine concentrations, baseline estimated glomerular filtration rate (eGFR), white blood cell count, platelet count, and hemoglobin levels were measured. The eGFR was calculated using the Modification of Diet in Renal Disease study equation.23 Serum creatinine levels were measured daily postprocedure for at least 48 to 72 hours. The level of PCT was determined within 30 minutes using VIDAS BRAHMS PCT assay (BioMerieux Clinical Diagnostics., France), which is an enzyme-linked fluorescent immunoassay, performed in an automated VIDAS instrument (BioMerieux Inc, Marcy l’Etoile, France). The normal reference limit was accepted as
