Pentraxin 3 (PTX3), a multifunctional modulator of the innate immunoinflammatory response, is higher in patients undergoing hemodialysis than healthy control. Our study focused on annual change in PTX3 levels in patients with chronic hemodialysis, because regularly undergoing hemodialysis for many years modifies vascular inflammatory status. To demonstrate whether annual change in PTX3 is associated with vascular events, we measured blood levels of pentraxins (PTX3 and high-sensitivity C-reactive protein (hsCRP)) at baseline and in the next year in 76 hemodialysis patients and observed 20 patients with vascular access troubles during follow-up years. The annual decline in PTX3, but not hsCRP, is a significant risk of the incidence of vascular access trouble that is a critical and specific complication for hemodialysis patients (hazard ratio; 0.732 per +1 ng/mL/year in PTX3,
Inflammation in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) is associated with malnutrition and cardiovascular diseases and resulted in poor clinical outcome [
Boehme and colleagues first described that the PTX3 levels of HD patients with ESRD are higher than healthy subjects or ESRD patients without receiving HD [
Here we show that the annual decline in PTX3, but not high-sensitive CRP (hsCRP), is a risk of the incidence of vascular access trouble that is a critical and specific complication for HD patients. This study is the first to focus on the annual change of pentraxins in a HD cohort.
This study was approved by the Ethics Committee of Namegata General Hospital, Namegata, Ibaraki, Japan, and nonhospitalized patients who regularly received HD were enrolled in this observational cohort study. All subjects were approached prospectively and gave informed consent to the study. Exclusion criteria were the presence of clinical signs of acute infection, active vasculitis, active hepatitis, and HIV at the time of evaluation and willingness to participate in the study. Of the 89 subjects initially enrolled in the study during 2011, 4 subjects died, and another 9 subjects did not complete exact one-year follow-up, primarily because they transferred to other hospitals, thus yielding a total of 76 patients who completed the study. Clinical demographic data of the subjects at baseline are given in Table
Characteristics of the subjects with stratification by absence or presence of vascular access troubles.
Total ( |
Absence ( |
Presence ( |
||||
---|---|---|---|---|---|---|
Median | IQC | Median | IQC | Median | IQC | |
Gender (% man) | 60 | — | 64 | — | 45 | — |
Diabetes (%) | 41 | — | 38 | — | 50 | — |
Age (years) | 67 | 58–77 | 66 | 58–77 | 67 | 58–77 |
Dialysis-period (years) | 5.4 | 2.3–9.4 | 5.8 | 2.8–9.6 | 4 | 2.0–7.4 |
Body mass index (kg/m2) | 21.9 | 19.6–24.0 | 21.2 | 19.4–24.0 | 22.5 | 20.5–24.0 |
RAS-inhibitor usage (%) | 80 | — | 82 | — | 72 | — |
Statin usage (%) | 14 | — | 11 | — | 22 | — |
Total protein (g/dL) | 6.6 | 6.3–6.9 | 6.5 | 6.3–6.8 | 6.6 | 6.2–7.0 |
Albumin (g/dL) | 3.3 | 3.0–3.4 | 3.3 | 3.0–3.5 | 3.3 | 3.0–3.4 |
Calcium (mg/dL) | 8.9 | 8.5–9.8 | 8.8 | 8.4–9.8 | 9 | 8.6–9.9 |
Inorganic phosphorus (mg/dL) | 5.2 | 4.6–6.1 | 5.2 | 4.6–5.8 | 5.3 | 4.6–6.3 |
Total cholesterol (mg/dL) | 165 | 139–182 | 167 | 139–182 | 158 | 138–181 |
LDL-C (mg/dL) | 95 | 77–112 | 95 | 73–113 | 93 | 77–107 |
Triglyceride (mg/dL) | 93 | 72–145 | 93 | 74–136 | 97 | 72–174 |
Intact parathyroid hormone (pg/mL) | 109 | 70–157 | 114 | 75–159 | 79 | 48–130 |
Hemoglobin (g/dL) | 11 | 10.2–11.5 | 11 | 10.2–11.5 | 10.9 | 10.0–11.9 |
Ferritin (ng/mL) | 65.6 | 40.8–114.9 | 66.2 | 41.1–116.2 | 62.9 | 40.6–114.9 |
Serum iron (mg/dL) | 63.5 | 48.5–84.8 | 64 | 48.5–87.8 | 62 | 47.3–74.8 |
|
29.1 | 25.5–32.2 | 28.9 | 24.7–31.9 | 29.9 | 26.8–34.3 |
PTX3 (ng/mL) | 4.2 | 3.1–5.4 | 4.1 | 3.1–5.4 | 4.2 | 3.1–5.8 |
hsCRP (mg/dL) | 0.66 | 0.56–0.73 | 0.64 | 0.54–0.72 | 0.68 | 0.62–0.75 |
Data at baseline year was presented as median and interquartile range (IQC). RAS: renin-angiotensin system, LDL-C: low-density lipoprotein cholesterol, PTX3: pentraxin 3, and hsCRP: high-sensitivity C-reactive protein.
Blood samples were placed in chilled tubes containing ethylenediaminetetraacetic acid (2 mg/mL) or no anticoagulants and centrifuged at 5500 g for 10 min at 4°C; the obtained plasma or serum, respectively, was stored at −80°C until analysis. Plasma concentrations of PTX3 were determined by using a commercial human PTX3 enzyme-linked immunosorbent assay (ELISA) kit system (Perseus Proteomics, Tokyo, Japan). Serum concentrations of hsCRP were determined by using the nephelometric N-latex CRP II kit (Siemens Diagnostics, Erlangen, Germany). Serum level of intact parathyroid hormone was determined by using Elecsys immunoassay systems (Roche Diagnostics, Basel, Switzerland).
Values in tables are expressed as median with interquartile range (IQR). Statistical significance was set at
Characteristic of this study population is shown in Table
Comparison of pentraxin levels in baseline year among the subpopulations.
Mean | SD | Mean | SD |
|
|
---|---|---|---|---|---|
Sex | Male ( |
Female ( |
|||
Pentraxin 3 | 4.627 | 2.722 | 4.466 | 1.27 | 0.731 |
hsCRP | 0.658 | 0.126 | 0.685 | 0.182 | 0.474 |
|
|||||
DM | Non-DM ( |
DM ( |
|||
Pentraxin 3 | 4.946 | 2.422 | 4.005 | 1.83 | 0.058 |
hsCRP | 0.675 | 0.18 | 0.661 | 0.096 | 0.656 |
|
|||||
Age | <65 years ( |
≥65 years ( |
|||
Pentraxin 3 | 4.447 | 1.898 | 4.64 | 2.459 | 0.701 |
hsCRP | 0.661 | 0.15 | 0.674 | 0.153 | 0.71 |
|
|||||
Dialysis-period | <5 years ( |
≥5 years ( |
|||
Pentraxin 3 | 3.961 | 1.852 | 5.048 | 2.416 |
0.03 |
hsCRP | 0.66 | 0.127 | 0.676 | 0.168 | 0.641 |
|
|||||
Body mass index | ≥22 kg/m2 ( |
<22 kg/m2 ( |
|||
Pentraxin 3 | 5.175 | 2.397 | 3.719 | 1.689 | 0.00 |
hsCRP | 0.649 | 0.178 | 0.683 | 0.127 | 0.36 |
Data at baseline year was presented. Values of pentraxin 3 or hsCRP are expressed by ng/mL or mg/dL. DM: diabetes mellitus; hsCRP: high-sensitivity C-reactive protein.
Because increased level of PTX3 would be dependent on length of dialysis-period as shown in Table
The annual change in pentraxins in the HD cohort. Distribution of annual change in PTX3 levels (ΔPTX3 (a)) or hsCRP (ΔhsCRP (b)) of the whole subjects is shown.
To know the pathophysiological implications of annual change in pentraxin levels in HD patients, we examined whether pentraxins can predict the incidence of vascular events by utilizing cox-regression model. The number of patients with vascular access trouble during follow-up years (from 2011 to the end of 2013) was twenty. Table
Cox-regression models for the incidence of vascular access troubles with or without multivariable adjustment.
Unadjusted |
Adjusted by DM, sex, | |||||
---|---|---|---|---|---|---|
Hazard ratio | 95% C.I. |
|
Hazard ratio | 95% C.I. |
|
|
Baseline PTX3 | 1.006 | 0.836–1.211 | 0.951 | 1.237 | 0.936–1.635 | 0.136 |
|
0.849 | 0.680–1.061 | 0.151 | 0.732 | 0.544–0.985 | 0.03 |
Baseline hsCRP | 3.644 | 0.469–28.30 | 0.216 | 2.713 | 0.389–18.92 | 0.314 |
|
9.486 | 0.108–833.2 | 0.324 | 3.605 | 0.033–394.7 | 0.592 |
The incidence of vascular access troubles during follow-up years was set as the outcome. Covariants examined in Table
Baseline levels and annual change in pentraxins in subjects with vascular access troubles. Mean ± S.E.M. in baseline year (a) or annual change (b) of pentraxins in the subjects without or with vascular access troubles (− or +,
PTX3 is produced by various types of cells and increases rapidly in response to primary local inflammation and innate immunity [
Recently, notable results were described in PTX3-deficient murine experiments; the elevation of PTX3 during cardiovascular diseases has recently been postulated to be a compensatory response to protect the body from inflammation [
Although cross-sectional studies with a single measurement of pentraxins are available [
PTX3 is produced by various stimuli including lipopolysaccharide and cytokines such as tumor necrosis factor and interleukin-1
Recently, some report suggested a crucial protective role of PTX3 in thrombotic diseases. In acute myocardial infraction, depletion of intracellular PTX3 in neutrophils correlates with increased plasma levels and with platelet-neutrophil aggregates
In this research, by serial measurements of levels of PTX3, here we show that the annual decline in PTX3, but not in hsCRP, is a risk of the incidence vascular access troubles that is a critical complication for HD patients. This is the noteworthy study to focus on the annual change in pentraxins in a HD cohort and to support the evidence for the function of PTX3 to protect bodies from vascular thrombotic events.
The authors declare having no conflict of interests or funding interest in connection with the publication of this paper.