Original Paper Received: November 28, 2014 Accepted: February 24, 2015 Published online: April 29, 2015
Blood Purif 2015;39:266–273 DOI: 10.1159/000381254
Plasma Pentraxin 3 Is Closely Associated with Peripheral Arterial Disease in Hemodialysis Patients and Predicts Clinical Outcome: A 6-Year Follow-Up Yijun Zhou a, b Jiwei Zhang c Mingli Zhu b Renhua Lu b Yongmei Wang b Zhaohui Ni b
a Shanghai Jiao Tong University School of Medicine, b Department of Nephrology, and c Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Key Words Ankle-brachial index · Inflammation · Atherosclerosis · Follow-up studies
hsCRP. Furthermore, PTX3 was also a predictor of all-cause mortality in HD patients. PTX3 may be considered a novel biomarker of inflammation in HD patients. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0253–5068/15/0394–0266$39.50/0 E-Mail [email protected] www.karger.com/bpu
Introduction
Approximately, 50% of deaths among the patients with end-stage renal disease (ESRD) originate from cardiovascular disease (CVD) [1]. Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is common among ESRD patients [1]. Some experts have begun to pay attention to the importance of PAD and its biomarkers [2]. Recent data suggest that PAD is a strong predictor for overall mortality in hemodialysis (HD) patients [3, 4]. Traditional risk factors alone do not explain the unacceptably high prevalence and incidence of CVD in ESRD patients [5]. The search for nontraditional risk factors that may be involved in the pathogenesis of CVD in these patients, especially for chronic inflammation, has become an area of intense investigation. Moreover, it is increasingly recognized that chronic kidney disease (CKD) is associated with a state of persistent microinflammation [6]. Zhaohui Ni Ren Ji Hospital 160 Pujian Road Shanghai 200127 (China) E-Mail nizhaohui2012 @ 126.com
Downloaded by: Siriraj Medical Library, Mahidol University 198.143.39.97 - 1/27/2016 10:39:58 PM
Abstract Background: The aim of this study is to investigate the value of plasma PTX3 level for assessing peripheral artery disease (PAD) and clinical outcome in hemodialysis (HD) patients. Methods: The ankle-brachial index (ABI) was measured in HD patients. PTX3 levels in 116 HD patients were measured by ELISA. Results: Overall, 116 HD patients were enrolled; 21 (18%) patients had PAD. Using the ROC curve analysis for PAD, PTX3 (cut-off value 4.06 ng/ml, AUC 0.901, p < 0.0001) showed a significantly better positive predictive value than hsCRP (cut-off value 3.33 ng/ml, AUC 0.640, p < 0.05). During follow-up (mean 57 ± 26 months), 40 deaths (34%) occurred. Kaplan-Meier analysis found that those patients with elevated PTX3 had a significantly poor outcome (p < 0.0001), and Cox analysis further confirmed that PTX3 was an independent predictor of overall mortality (HR, 1.105, p = 0.03). For prediction of overall mortality, the AUC for PTX3 (cut-off value 3.22 ng/ml, AUC 0.690, p < 0.0001) was close to hsCRP (cut-off value 5.84 ng/ml, AUC 0.620, p < 0.001). Conclusions: For the prediction of PAD in HD patients, the diagnostic sensitivity and specificity of PTX3 were higher than those of
Methods Patients We enrolled HD patients from the dialysis center of Renji Hospital, Shanghai, China, between May and July 2008. Inclusion criteria were stable HD for at least 3 months at the time of evaluation and ability and willingness to provide informed consent. All patients were dialyzed on synthetic (polysulfone) membranes with bicarbonate dialysate. Exclusion criteria consisted of (1) severe medical conditions (e.g. cancer, sepsis, advanced liver or lung disease, and severe heart failure); (2) active tuberculosis, systemic lupus erythematosus, systemic vasculitis, or rheumatoid arthritis; and (3) peritoneal dialysis or kidney transplantation patients who were converted to HD.
dure and/or angiography findings. The ABI was measured in all HD patients using an ABI device (MICROLITE 84M/0289, Sony) by a professional technician; the device measures arm and ankle (brachial and posterior tibial arteries, respectively) blood pressure by an ultrasonic technique. The measurement was obtained after completion of the dialysis treatment and after allowing patients to rest in a supine position at least for 5 min. The ABI was calculated by the ratio of the ankle systolic pressure divided by the arm systolic pressure. The systolic pressure of the arm without dialysis access and the lower value of the ankle pressure were used for the calculation. The CVD was defined as a previous angiogram showing significant occlusive disease, a history of a myocardial infarction, a history of coronary artery bypass surgery or angioplasty, or a history of a cerebrovascular accident, including cerebral bleeding and infarction. PTX3 and hsCRP Measurement Blood was drawn with EDTA anticoagulant in the morning after an overnight fast of at least 12 h before a dialysis session. The samples were separated via centrifugation (4,000 rpm, 10 min) and immediately stored at –80 ° C for subsequent assays. The plasma concentrations of PTX3 were evaluated using an ELISA kit (R&D Systems, USA). Concentrations of high-sensitivity C-reactive protein (hsCRP) were conducted in our central testing laboratory and were measured by an immune turbidity method (Orion Diagnostica, Finland).
Follow-Up and Outcome Analyses Clinical outcome in this study included actual patient survival. The observation period ended on 31st August 2014. At the end of the follow-up, the status of all patients was assessed, and data on mortality were obtained for the entire cohort.
Definition The PAD was defined based on clinical symptoms (intermittent claudication, which evolves to pain at rest and a risk of tissue necrosis, and even to amputation), ABI of
Blood Purif 2015;39:266–273 DOI: 10.1159/000381254
Plasma Pentraxin 3 Is Closely Associated with Peripheral Arterial Disease in Hemodialysis Patients and Predicts Clinical Outcome: A 6-Year Follow-Up Yijun Zhou a, b Jiwei Zhang c Mingli Zhu b Renhua Lu b Yongmei Wang b Zhaohui Ni b
a Shanghai Jiao Tong University School of Medicine, b Department of Nephrology, and c Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Key Words Ankle-brachial index · Inflammation · Atherosclerosis · Follow-up studies
hsCRP. Furthermore, PTX3 was also a predictor of all-cause mortality in HD patients. PTX3 may be considered a novel biomarker of inflammation in HD patients. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0253–5068/15/0394–0266$39.50/0 E-Mail [email protected] www.karger.com/bpu
Introduction
Approximately, 50% of deaths among the patients with end-stage renal disease (ESRD) originate from cardiovascular disease (CVD) [1]. Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is common among ESRD patients [1]. Some experts have begun to pay attention to the importance of PAD and its biomarkers [2]. Recent data suggest that PAD is a strong predictor for overall mortality in hemodialysis (HD) patients [3, 4]. Traditional risk factors alone do not explain the unacceptably high prevalence and incidence of CVD in ESRD patients [5]. The search for nontraditional risk factors that may be involved in the pathogenesis of CVD in these patients, especially for chronic inflammation, has become an area of intense investigation. Moreover, it is increasingly recognized that chronic kidney disease (CKD) is associated with a state of persistent microinflammation [6]. Zhaohui Ni Ren Ji Hospital 160 Pujian Road Shanghai 200127 (China) E-Mail nizhaohui2012 @ 126.com
Downloaded by: Siriraj Medical Library, Mahidol University 198.143.39.97 - 1/27/2016 10:39:58 PM
Abstract Background: The aim of this study is to investigate the value of plasma PTX3 level for assessing peripheral artery disease (PAD) and clinical outcome in hemodialysis (HD) patients. Methods: The ankle-brachial index (ABI) was measured in HD patients. PTX3 levels in 116 HD patients were measured by ELISA. Results: Overall, 116 HD patients were enrolled; 21 (18%) patients had PAD. Using the ROC curve analysis for PAD, PTX3 (cut-off value 4.06 ng/ml, AUC 0.901, p < 0.0001) showed a significantly better positive predictive value than hsCRP (cut-off value 3.33 ng/ml, AUC 0.640, p < 0.05). During follow-up (mean 57 ± 26 months), 40 deaths (34%) occurred. Kaplan-Meier analysis found that those patients with elevated PTX3 had a significantly poor outcome (p < 0.0001), and Cox analysis further confirmed that PTX3 was an independent predictor of overall mortality (HR, 1.105, p = 0.03). For prediction of overall mortality, the AUC for PTX3 (cut-off value 3.22 ng/ml, AUC 0.690, p < 0.0001) was close to hsCRP (cut-off value 5.84 ng/ml, AUC 0.620, p < 0.001). Conclusions: For the prediction of PAD in HD patients, the diagnostic sensitivity and specificity of PTX3 were higher than those of
Methods Patients We enrolled HD patients from the dialysis center of Renji Hospital, Shanghai, China, between May and July 2008. Inclusion criteria were stable HD for at least 3 months at the time of evaluation and ability and willingness to provide informed consent. All patients were dialyzed on synthetic (polysulfone) membranes with bicarbonate dialysate. Exclusion criteria consisted of (1) severe medical conditions (e.g. cancer, sepsis, advanced liver or lung disease, and severe heart failure); (2) active tuberculosis, systemic lupus erythematosus, systemic vasculitis, or rheumatoid arthritis; and (3) peritoneal dialysis or kidney transplantation patients who were converted to HD.
dure and/or angiography findings. The ABI was measured in all HD patients using an ABI device (MICROLITE 84M/0289, Sony) by a professional technician; the device measures arm and ankle (brachial and posterior tibial arteries, respectively) blood pressure by an ultrasonic technique. The measurement was obtained after completion of the dialysis treatment and after allowing patients to rest in a supine position at least for 5 min. The ABI was calculated by the ratio of the ankle systolic pressure divided by the arm systolic pressure. The systolic pressure of the arm without dialysis access and the lower value of the ankle pressure were used for the calculation. The CVD was defined as a previous angiogram showing significant occlusive disease, a history of a myocardial infarction, a history of coronary artery bypass surgery or angioplasty, or a history of a cerebrovascular accident, including cerebral bleeding and infarction. PTX3 and hsCRP Measurement Blood was drawn with EDTA anticoagulant in the morning after an overnight fast of at least 12 h before a dialysis session. The samples were separated via centrifugation (4,000 rpm, 10 min) and immediately stored at –80 ° C for subsequent assays. The plasma concentrations of PTX3 were evaluated using an ELISA kit (R&D Systems, USA). Concentrations of high-sensitivity C-reactive protein (hsCRP) were conducted in our central testing laboratory and were measured by an immune turbidity method (Orion Diagnostica, Finland).
Follow-Up and Outcome Analyses Clinical outcome in this study included actual patient survival. The observation period ended on 31st August 2014. At the end of the follow-up, the status of all patients was assessed, and data on mortality were obtained for the entire cohort.
Definition The PAD was defined based on clinical symptoms (intermittent claudication, which evolves to pain at rest and a risk of tissue necrosis, and even to amputation), ABI of
