|Year : 2018 | Volume
| Issue : 1 | Page : 11-16
Procalcitonin as an inflammatory marker in comparison between high-flux and low-flux hemodialysis in patients with end-stage renal disease
Hesham M El Sayed, Hussein S Hussein, Sabah A Hammad
Department of Nephrology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||19-Nov-2017|
|Date of Acceptance||18-Jan-2018|
|Date of Web Publication||02-May-2018|
Prof. Hesham M El Sayed
Prof. of Internal Medicine and Nephrology Nephrology Department, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Background Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in hemodialysis (HD) patients.
Patients and methods We measured PCT serum levels and high-sensitivity C-reactive protein (hs-CRP) before and immediately after HD in 50 adult HD patients (25 treated with high-flux membranes and 25 with low-flux membranes), without history of concurrent infections.
Results The baseline PCT levels before HD were higher than healthy individuals. There was a highly significant decrease in PCT serum levels after HD session in patients undergoing HD by high-flux membranes but not by low-flux membranes (high flux 0.54 ng/ml pre-HD vs. 0.26 ng/ml post-HD, P=0.001, whereas in low flux 0.50 ng/ml vs. 0.53 ng/ml, P=0.066). Hs-CRP levels were unchanged in both groups. There was no correlation between PCT and CRP.
Conclusion Although PCT is considered a sensitive and specific diagnostic and prognostic marker of systemic bacterial infection, we suggest that specific reference ranges might be developed in patients with impaired renal function; moreover, its clinical usefulness might be limited in patients undergoing HD with high-flux membranes.
Keywords: chronic renal failure (CRF), C-reactive protein, hemodialysis, hemodialysis membrane inflammation, procalcitonin
|How to cite this article:|
El Sayed HM, Hussein HS, Hammad SA. Procalcitonin as an inflammatory marker in comparison between high-flux and low-flux hemodialysis in patients with end-stage renal disease. J Egypt Soc Nephrol Transplant 2018;18:11-6
|How to cite this URL:|
El Sayed HM, Hussein HS, Hammad SA. Procalcitonin as an inflammatory marker in comparison between high-flux and low-flux hemodialysis in patients with end-stage renal disease. J Egypt Soc Nephrol Transplant [serial online] 2018 [cited 2018 Aug 17];18:11-6. Available from: http://www.jesnt.eg.net/text.asp?2018/18/1/11/231749
| Introduction|| |
Chronic kidney disease (CKD) is a significant public health dilemma with an advanced requirement for dialysis either hemodialysis (HD) or peritoneal dialysis every year. The increased risk of infection in patients with CKD has been demonstrated, especially in those treated with long-term HD .
Health-related quality of life has been associated with nutritional outcomes, hospitalizations, and survival in patients with end-stage renal disease (ESRD). Quality of life in patients with ESRD on dialysis is also dependent on the quality of dialysis .
In total, three general types of dialysis membranes are available at present: unmodified cellulose (low flux, namely, ‘bio-incompatible’ membranes), modified/regenerated cellulose (low flux or high flux, namely, ‘relatively biocompatible’), and synthetic (low flux or high flux, namely, ‘relatively biocompatible’) .
The choice of a dialysis membrane should take into account the following: biocompatibility of the material toward leukocytes and complement activation; blood volume priming requirement, which is membrane area related; and permeability, determined in the simplest way by two characteristics of hydraulic permeability and molecular permeability determined at least by molecular weight of the molecule considered .
Uremic toxins are classified into three groups : small (500 Da) water-soluble molecules such as urea, sodium, and phosphate, which are rapidly produced in intracellular compartment and are efficiently removed by most filters; middle-sized (500–40 000 Da) water-soluble molecules such as B2-microglobulin, parathyroid hormone, and some cytokines (interleukin-6 and tumor necrotizing factor) that require optimized filter design and convection for removal; and small (500 Da) but protein-bound molecules which are poorly removed with traditional dialysis .
In fact low-flux membranes do not remove middle-sized molecule toxin, but highly permeable membranes are efficient in removal of both small non-protein-bound and middle-sized uremic toxins .
Recurrent or chronic inflammatory processes are common in individuals with ESRD. This is owing to many underlying factors, including the uremic milieu, elevated levels of circulating proinflammatory cytokines, oxidative stress, carbonyl stress, protein-energy wasting, and enhanced incidence of infections (especially dialysis-access related) .
Currently applied laboratory markers of inflammation can be misleading in these patients because of uremia or HD. Some of these parameters may be none specifically decreased, such as white blood count and others may be none specifically increased such as erythrocyte sedimentation rate and C-reactive protein (CRP) .
Procalcitonin (PCT) is the precursor protein of calcitonin, a calcium regulatory hormone; it is a polypeptide of 116 amino acids with a molecular weight of 13 kDa and normally produced in the C-cells of the thyroid gland. Production of PCT is regulated by the Calc-1 gene which is located on chromosome 11. Calc-1 codes for pre-PCT, which undergoes proteolytic cleavage of its signal sequence to produce the definitive PCT molecule .
PCT testing increases the specificity of the diagnosis of bacterial infection more than testing for other inflammatory markers, such as CRP or leukocytic counts . However, other conditions, not associated with infections, such as early postoperative state, trauma, severe burns, leucopenia, and renal dysfunction can also increase serum PCT . Additionally, it has been shown that serum PCT levels are high in patients with reduced renal function and that these levels are reduced after dialysis .
The serum PCT level in healthy individuals is less than 0.3 ng/ml. In the life-threatening septic condition owing to severe bacterial infection, the serum PCT level exceeds 0.5 ng/ml. Herget-Rosenthal et al.  used the cutoff point of 1.5 ng/ml for detection of sepsis in hemodialytic patients.
PCT may aid in differentiating sepsis from systemic inflammatory response syndrome and serve as a monitor for the activity of infection . An increase in serum PCT is detectable 4 h after endotoxemia. Serum PCT peaks 6 h after endotoxemia and has a serum half-life of 25–30 h . The aim of our study was to evaluate the changes in the serum levels of PCT and its correlation to the traditional inflammatory marker CRP and also to identify the potential influence of different types of membrane (either low or high flux) on PCT clearance.
| Patients and methods|| |
This prospective comparative study included 50 adult patients with ESRD older than 18 years and clinically stable patients on regular HD for at least 6 months before the study selected from dialysis unit in Kom Hamada General Hospital, El Beheira Governorate, Egypt, with a written informed consent for participation in this study. All patients were free from clinical signs of systemic infections before the study. They are classified into two groups:
- Group I (high-flux dialysis group) included 25 patients with ESRD maintained on HD using Allmed platinum H3 polysulphone high-flux membrane, steam sterilized, with a surface area of 1.6 m2 for at least 6 months.
- Group II (low-flux dialysis group) included 25 patients with ESRD maintained on HD using platinum M3 polysulphone low-flux membrane, steam sterilized, with a surface area of 1.6 m2 for at least 6 months.
None of the patients had overt inflammatory disease within the past 2 months or showed evidence of malignancy, liver abnormalities, or hypothyroidism. Patients affected by chronic viral infections (chronic hepatitis B or C) or chronic active infection (e.g. tuberculosis, infected shunt), patients with active collagen disease, and patients with acute illness were not included in the study. Criteria to exclude current infection were temperature less than 38°C and leukocyte count less than 10 000 cells/µl.
HD treatment was performed for 3.5–4 h three times per week, using bicarbonate buffered dialysate, with unfractionated heparin for anticoagulation. The blood flow rate was between 200 and 350 ml/h, and ultrafiltration rate was between 300 and 1000 ml/h. The water treatment system consisted of simple reverse osmosis, disinfected weekly, and all dialysis generators were disinfected after each dialysis procedure. Regular microbiological tests showed no bacterial growth in the dialysis water ([Figure 1],[Figure 2],[Figure 3],[Figure 4]).
|Figure 1 Comparison between procalcitonin before and after dialysis in group I (high-flux group).|
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|Figure 2 Comparison between procalcitonin before and after dialysis in group II (low-flux group).|
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|Figure 3 Comparison between high-sensitivity C-reactive protein before and after dialysis in group I (high-flux group).|
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|Figure 4 Comparison between high-sensitivity C-reactive protein before and after dialysis in group II (low-flux group).|
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Samples were collected from arteriovenous fistula immediately before (pre-HD) and 5 min after the end of HD session (post-HD) into tubes. Immediate centrifugation was done for 10 min at 5000 rpm. All samples were stored at −7°C until the time of the assay.
Investigated laboratory parameters
- Complete blood count.
- Blood urea.
- Serum creatinine level (modified rate gaffe method).
- PCT levels before HD and after HD using human procalcitonin enzyme-linked immunosorbent assay. PCT is measured using kits supplied from Brahms Aktiengesellschaft (BRAHMS, Hennigsdorf, Germany), BRAHMS KRYPTOR, which is used for quantitative measurement of PCT in human serum and plasma (Germany).
- Hs-CRP before and after HD using high-sensitivity C-reactive protein ELISA Kit (Phoenix Pharmaceuticals Inc., Burlingame, CA, USA).
- Serum calcium and phosphorus.
- Serum albumin.
- Data were analyzed on an IBM personal computer, using statistical package for special sciences (SPSS) software computer program version 17 (SPSS Inc., Chicago, Illinois, USA).
- Qualitative data were expressed in number and percentage, and quantitative data were described as mean±SD. Independent sample t-test was used for comparison of quantitative variables among the two groups.
- Pre-HD and post-HD measurements of PCT and high-sensitivity C-reactive protein (hs-CRP) were compared between the two groups using paired samples t-test. P value less than 0.05 was considered statistically significant.
| Results|| |
This study included 50 adult patients with ESRD on regular HD. The patients were divided into two groups according to the type of HD membrane.
- Group I included 25 patients undergoing HD by high-flux membranes.
- Group II included 25 patients undergoing HD by low-flux membranes.
No statistically significant difference was found between the two studied groups regarding age, sex, duration on HD, and BMI ([Table 1]).
|Table 1 Characteristics of the studied groups: comparison regarding demographic data|
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There was no statistically significant difference between the two studied groups regarding the etiology of ESRD. In group I, the etiology of ESRD was hypertension in 12 (48%) patients, DM in four (16%), idiopathic in three (12%), obstructive nephropathy in four (16%), and due to polycystic kidney in two (8%). However, in the group II, hypertension was present in 13 (52%) patients, DM in five (20%), two (8%) idiopathic, four (16%) owing to obstructive nephropathy, and one (4%) owing to analgesic nephropathy.
There was a statistically significant difference between two groups regarding urea reduction ratio (URR%) and serum phosphorus ([Table 2]).
|Table 2 Comparison between two groups regarding laboratory investigations|
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There was a highly significant decrease in PCT serum levels after HD session by high-flux membranes (P=0.001). However, there was no statistically significant difference between pre-HD and post-HD PCT levels in group II ([Table 3]).
|Table 3 Comparison between procalcitonin before and after dialysis between group I (high flux) and group II (low flux)|
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There was no statistically significant difference between pre-HD and post-HD hs-CRP values in group I and group II ([Table 4]).
|Table 4 Comparison between high-sensitivity C-reactive protein before and after dialysis between group I (high-flux) and group II (low-flux)|
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There was statistically significant positive correlation between predialysis PCT and duration of HD, URR%, and Kt/v in group I. However, there was no statistically significant correlation between predialysis PCT, other demographic, and laboratory investigations ([Table 5]).
|Table 5 Correlation between predialysis procalcitonin and laboratory investigations before dialysis and demographic data in group I (high flux) and group II (low flux)|
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| Discussion|| |
PCT is mostly synthesized and released as part of the systemic response to circulating endotoxins and cytokines during bacterial and fungal infection. Some studies have demonstrated that the plasma level of PCT correlates with the severity of infection, and that PCT concentration is useful to discriminate between septic complications and noninfectious inflammatory reactions in critically ill patients .
In the present study, there was no statistically significant difference between the two studied groups regarding age, sex, duration of HD, BMI, and the etiology of ESRD.
Ichihara et al.  demonstrated that the PCT level can be elevated in patients with renal insufficiency as PCT is a low-molecular-weight protein that can be filtered by the renal glomerulus and absorbed by the renal tubules.
Herget-Rosenthal et al.  reported that the PCT level gradually increased according to the degree of deterioration in renal function and was influenced by the type of the renal replacement therapy.
In our study, we demonstrated that PCT levels might be significantly influenced by HD. We observed a significant decrease in PCT concentrations after HD (post-HD) in patients undergoing HD with high-flux membranes (P<0.001), with a decrease ranging from 5 to 85% of serum PCT levels after HD session. However, in low-flux group, there was no significant change between predialysis and postdialysis PCT levels.
This in line with the results observed by Montagnana et al.  (22 patient on high-flux membranes and 22 on low-flux membranes, and they were followed up for 1 year) who observed a significant decrease in serum PCT concentrations in patients undergoing HD by high-flux membranes.
Moreover, our results meet with the study done by Grace and turner, who demonstrated that patients with CKD started on RRT have displayed the most significant decrease in PCT levels following a 4 h session of high-flux hemodialysis compared with all other forms of RRT, and the magnitude of drop in PCT levels following high-flux hemodialysis has been attributed to the high permeability of PCT through the dialysis filter. Moreover, the studies have failed to show a significant decrease in PCT following low-flux hemodialysis .
In the current study while comparing hs-CRP pre-HD and post-HD session for both groups, it was found that there was no statistically significant difference regarding hs-CRP in both groups. This meets with the study done by Akbulut et al.  who reported that hs-CRP levels were unchanged before and after HD by both high-flux and low-flux membranes. In addition, they demonstrated that lack of significant difference in the CRP levels after HD indicated that CRP was not eliminated with HD, and HD had no significant effect on CRP levels .The current study showed that there was statistically significant positive correlation between predialysis PCT in group I and duration of HD, URR, and Kt/v. Moreover, there was no statistically significant difference between postdialysis PCT and postdialysis hs-CRP in both group I and group II.
In line with our results, Level et al.  in their cohort study of 63 chronic noninfected HD patients found no relationship between PCT and other inflammatory parameters such as CRP.
In contrast with our results, Level et al.  found a close relationship between PCT and other inflammatory parameters such as CRP. Moreover, a study done by Akbulut et al.  demonstrated that PCT and CRP concentrations are weakly correlated before HD. Ichihara et al.  also found a significant correlation between PCT and CRP.
| Conclusion|| |
Although PCT is currently considered a sensitive and specific diagnostic and prognostic marker of systemic bacterial infections, we suggest that specific reference ranges might be developed in patients with impaired renal function. We have also shown that the clinical value of PCT testing might be limited in patients undergoing HD with high-flux membranes. PCT is a marker of inflammation in HD patients after exclusion of infection and not correlated significantly to CRP.
PCT should be measured before HD session in patients undergoing HD with high-flux membranes. However, further larger studies are needed to confirm the results.
We acknowledged, however, that a weakness of this study might be the limited number of participants enrolled. Therefore, our results should be confirmed in larger population of HD patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]