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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 946-951

Study of tumor necrosis factor-α in postdialysis fatigue patients


1 Department of Internal Medicine and Nephrology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Internal Medicine, El Sahel Teaching Hospital, Cairo, Egypt

Date of Submission13-Jan-2018
Date of Acceptance03-Mar-2018
Date of Web Publication31-Dec-2018

Correspondence Address:
Mohamed S.H Aboelmagd
Menouf City, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_10_18

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  Abstract 


Objective
The aim was to study the tumor necrosis factor-α in postdialysis fatigue (PDF).
Background
Fatigue is one of the most frequent complaints of dialysis patients and is associated with impaired health-related quality of life.
Patients and methods
A cross-sectional study was conducted on 50 patients receiving hemodialysis treatment who were divided into two groups: group I included 25 patients with PDF, and group II included 25 patients without PDF. All patients attended the Dialysis Unit at Menoufia University Hospital and El Sahel Teaching Hospital in the period from January to October 2017. Demographic, clinical, and laboratory data were recorded for each patient.
Results
A total of 50 patients were included in the current study. The mean age of group I was 50.20 ± 13.02 years and of group II was 46.76 ± 13.40 years. There was a statistically significant difference between the studied groups regarding sex (P = 0.045), education levels (P = 0.029), weight change (P = 0.001), predialysis diastolic blood pressure (P = 0.016), postdialysis diastolic blood pressure (P = 0.004), hemoglobin (P = 0.001), calcium (P = 0.035), albumin (P = 0.040), and C-reactive protein (P = 0.007).
Conclusion
Our results concluded that excessive ultrafiltration, intradialytic hypotension, anemia, hypocalcemia, malnutrition, and C-reactive protein were statistically significantly increased in postdialysis fatigue (PDF) group compared with non-PDF. Moreover, there is a lack of correlation between tumor necrosis factor-α and PDF. Finally, it is crucial to design adequate studies to understand the mechanism of PDF, and more importantly, for developing effective therapeutic strategies.

Keywords: enzyme-linked immunosorbent assay kit, fatigue, hemodialysis, postdialysis, tumor necrosis factor-α


How to cite this article:
Khamis SS, Yassein YS, Zahran AM, El-Shazly RM, Aboelmagd MS. Study of tumor necrosis factor-α in postdialysis fatigue patients. Menoufia Med J 2018;31:946-51

How to cite this URL:
Khamis SS, Yassein YS, Zahran AM, El-Shazly RM, Aboelmagd MS. Study of tumor necrosis factor-α in postdialysis fatigue patients. Menoufia Med J [serial online] 2018 [cited 2019 Mar 25];31:946-51. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/946/248712




  Introduction Top


Fatigue is one of the most frequent complaints of dialysis patients and is associated with impaired health-related quality of life. The importance of fatigue to patients with kidney disease is underscored by the observation that 94% of hemodialysis (HD) patients endorsed a willingness to undergo more frequent dialysis if there would be an associated increase in energy level[1],[2],[3]. Postdialysis fatigue (PDF) is a distressing complaint, which is described as a feeling tiredness and in need of rest or sleep after the dialytic session. Patients with PDF experienced limitations in their functional independence and participation in social activities on the day of dialysis[4]. PDF is a common, often incapacitating symptom and may be improved with more frequent treatment. Lindsay, looked at PDF in 45 participants and found a positive association between ‘time to recover’ (minutes) from HD and fatigue; patients with longer recovery time tended to have greater levels of fatigue[5]. Ultrafiltration, diffusion, osmotic disequilibrium, changes in blood pressure, blood membrane interactions, higher levels of tumor necrosis factor (TNF), and psychological factors like depression have all been implicated in the pathogenesis of PDF[6]. A few physiological disorders are associated with fatigue, including anemia and other chronic illnesses such as rheumatoid arthritis, infection, and renal disease. Anemia reduces the oxygen supply to the tissues and is frequently cited as one of the main contributing factors to fatigue in renal failure, resulting from reduced erythropoietin production. Fatigue may indicate to the individual that illness is present and motivate them to seek treatment. Unfortunately, little is known about the prevalence and underlying mechanisms of PDF[7]. Similarly, no consensus exists on how to diagnose PDF and grade its severity. Small-scale studies suggest that PDF may be correlated with sociodemographic factors (e.g., age, sex, race, employments status, marital status, education, and social support), clinical variables (e.g., anemia, malnutrition, sleep disorders, secondary hyperparathyroidism, physical inactivity, number, and severity of comorbid conditions), as well as psychological (e.g. anxiety, stress, and depression) and dialysis-related factors[8],[9],[10],[11]. Yet, conflicting findings have been reported. The aim of this work was to study the TNFα in PDF.


  Patients and Methods Top


A cross-sectional study was conducted on 50 patients receiving HD treatment who attended the Dialysis Unit at Menoufia University Hospital and El Sahel Teaching Hospital in the period from January to October 2017.

Ethical consideration

All participants were volunteers. All of them signed an informed written consent after getting an explanation regarding the purpose of this study before the study initiation. The consent form was taken according to the standard in Quality Improvement System in Ministry of Health in Egypt, which was modified according to international ethical guidelines for Biochemical Research involving human participants as prepared by the Council for Faculty of Medicine, Menoufia University, Egypt.

All patients included in the study were randomly divided into two groups as follows:

  1. Group I included 25 patients (11 males and 14 females) with PDF
  2. Group II included 25 patients (18 males and seven females) with non-PDF.


Inclusion criteria

The inclusion criteria included patients who were on regular HD, with age 18 years or older, on HD for at least 6 months duration, with mental competence, and willingness to participate in the study.

Exclusion criteria

Patients with HD less than 6 months, HIV positive, previous long-term systemic treatment with immunosuppressive drugs. life-threatening malignancy or current multiple myeloma, pregnant or lactating, demyelinating disease, lack of ability to comply to the protocol, heart failure, endogenous depression, and recent infection were included from the study.

The total number of patients who were on HD at mentioned dialysis centers at the beginning of the study was 57 patients. After excluding patients who had seroconversion to HCV (two patients), three patients who died, one patient who got pregnant, and patients who were on regular dialysis for less than 3 months (one patients), 50 patients met our inclusion criteria and were included in the study.

All patients were subjected to the following: demographic data, for example age, sex, marital status, educational level, and occupation; clinical data, for example, weight before and after dialysis (kg), weight change, diastolic blood pressure (DBP), and systolic blood pressure (SBP) before and dialysis; laboratory investigation, for example, serum levels of albumin, creatinine, calcium, phosphorus, parathyroid hormone, hemoglobin (Hb), erythrocyte sediment rate, C-reactive protein (CRP), and iron study.

Quantitative measurement of TNFα in HD patients was done using enzyme-linked immunosorbent assay (ELISA) kit supplied by BOSTER Biological Technology (Human TNFα ELISA kit; Pleasanton, California, USA). Samples were collected after dialysis. Weight gain (median of the last 10 HD sessions) and interdialytic weight gain were expressed as percentage of dry weight and number of symptomatic intradialytic hypotensive events in the last 10 HD sessions.

Principle

Boster's human TNFα ELISA kit was based on standard sandwich ELISA assay technology. A monoclonal antibody from mouse specific for TNFα has been precoated into 96-well plates. Standards and test samples are added to the wells, and a biotinylated detection polyclonal antibody from goat specific for TNFα is added subsequently, and then followed by washing with PBS or TBS buffer. Avidin–biotin–peroxidase complex was added, and unbound conjugates were washed away with PBS or TBS buffer. Horseradish peroxidase (HRP) substrate transmembrane pressure (TMB) was used to visualize HRP enzymatic reaction. TMB was catalyzed by HRP to produce a blue color product that changed into yellow after adding acidic stop solution. The density of yellow is proportional to the human TNFα amount of sample captured in plate.

Assay procedure

The assay procedure is as follows: aliquot 0.1 ml per well of the 1000, 500, 250, 125, 62.5, 31.2, and 15.6 pg/ml human TNFα standard solutions into the precoated 96-well plate. Add 0.1 ml of the sample diluent buffer into the control well. Add 0.1 ml of each properly diluted sample of human cell culture supernatants, serum or plasma, to each empty well. Then seal the plate with the cover and incubate at 37°C for 90 min. Then remove the cover, discard plate content, and blot the plate onto paper towels or other absorbent material. Do not let the wells completely dry at any time. Then add 0.1 ml of biotinylated antihuman TNF-α antibody working solution into each well and incubate the plate at 37°C for 60 min. Then wash plate three times with 0.01 mol/l TBS or 0.01 mol/l PBS, and each time let washing buffer stay in the wells for 1 min. Discard the washing buffer and blot the plate onto paper towels or other absorbent material. Then add 0.1 ml of prepared avidin–biotin–peroxidase working solution into each well and incubate the plate at 37°C for 30 min. Then wash plate five times with 0.01 mol/l TBS or 0.01 mol/l PBS, and each time let washing buffer stay in the wells for 1–2 min. Discard the washing buffer and blot the plate onto paper towels or other absorbent material. Then add 90 μl of prepared TMB color developing agent into each well and incubate plate at 37°C in dark for 25–30 min, and then add 0.1 ml of prepared TMB stop solution into each well. The color changes into yellow immediately. Then read the optical density absorbance at 450 nm in a microplate reader within 30 min after adding the stop solution.

Statistical analysis

Results were analyzed and tabulated using Microsoft Excel version 7 (One Microsoft Way, Redmond, Washington, U.S.) and SPSS v. 16. (SPSS Inc., Chicago, Illinois, USA). Qualitative data were expressed as number and percentage and analyzed by using χ2. Quantitative data were expressed as mean ± SD and analyzed by using t-test, Mann–Whitney test, multiple regressions, and Wallis analysis of variance for comparing categorical data. A value of P less than 0.05 was indicated statistically significant.


  Results Top


A total of 50 patients were included in our study, including 29 (58%) male and 21 (42%) female patients. Mean age for PDF group was 50.20 ± 13.02 years, and 46.76 ± 13.40 years for non-PDF group. Overall, 56% of the PDF patients were female and 44% were male, whereas 72% of the non-PDF patients were male and 28% were female. There was statistical significant difference between the studied groups regarding sex (P = 0.045), education levels (P = 0.029), weight change (P = 0.001), predialysis DBP (P = 0.016), and postdialysis DBP (P = 0.004). The highest rate of fatigue was observed in patients with low education level. However, there were no statistical significant differences between the studied groups regarding age (P = 0.362), marital status (P = 0.191), occupation (P = 0.157), weight predialysis (P = 0.865), postdialysis (P = 0.847), predialysis SBP (P = 0.057), and postdialysis SBP (P = 0.178; [Table 1]).
Table 1: Comparison between the studied groups regarding demographic and clinical data

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Regarding laboratory investigation, there was a statistically significant difference between the studied groups regarding hemoglobin (P = 0.001), calcium (P = 0.035), albumin (P = 0.040), and CRP (P = 0.007), which were higher significantly in group II than group I. On the contrary, there were no statistical significant differences between the studied groups regarding PO4 (P = 0.332), total iron-binding capacity (P = 0.434), TNFα (P = 0.786), parathyroid hormone (P = 0.727), iron (P = 0.808), ferritin (P = 0.884), transferrin saturation (Tsat%) (P = 0.676), and erythrocyte sediment rate (P = 0.572; [Table 2]).
Table 2: Comparison between the studied groups regarding laboratory investigation

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Additionally, the logistic regression analysis indicated that there were significant predictors for fatigue identified regarding female sex, number of children (P = 0.002), hemoglobin (P = 0.000), calcium (P = 0.046), CRP (P = 0.020), albumin (P = 0.049), weight change (P = 0.001), and predialysis SBP (P = 0.024), with odds ratio 0.306, 0.449, 0.037, 0.367, 1.168, 0.182, 4.220, and 1.086, respectively [Table 3].
Table 3: Logistic regression analysis for predictors of fatigue

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Concerning, receiver operating characteristic curve of laboratory data predicting fatigue showed that using a cut-off point for Hb percentage less than or equal to 10.3 can be used to predict fatigue in HD with sensitivity of 88% and specificity of 92%, whereas, using a cut-off point for Ca less than or equal to 8.5 can be used to predict fatigue in HD with sensitivity of 48% and specificity of 92%. Moreover, using a cut-off point for CRP greater than 13 can be used to predict fatigue in HD with sensitivity of 48% and specificity of 88%. In addition, using a cut-off point for albumin less than or equal to 3.7 can be used to predict fatigue in HD with sensitivity of 36% and specificity of 96%. Moreover, using a cut-off point for weight change greater than 2 kg can be used to predict fatigue in HD with sensitivity of 60% and specificity of 84% [Table 4].
Table 4: Diagnostic performance of predictors of fatigue at the optimal cut-off points of the receiver operating characteristic analysis curve

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  Discussion Top


In the current study, there was no correlation between TNFα and PDF. This in contrast to Koyama et al.[8], who showed a significant intradialytic elevation of TNFα in PDF group. Moreover, there was no statistically significant difference between the two studied groups regarding the age of patients. This in an agreement with the findings of Kim and Son and others[12]. However, Bossola et al.[13] stated that fatigue in HD patients is common and correlated with age. There was a statistically significant difference between the studied groups regarding the sex of patients. These results are in agreement with Bossola et al.[13] who found that women have significantly higher fatigue levels than men. In contrast, Vatarii[14], found that a higher number of male participants with end-stage renal disease seems to be fatigued after dialysis.

In the present study, the highest rate of fatigue was observed in patients with low education level. This agrees with Mollaoglu and others[15],[16], who reported that higher education level helps the individual use some fatigue-relieving strategies. Moreover, Bonner et al.[17] indicate that fatigue was reduced by increasing educational level.

Additionally, in the current study, PDF was associated with postdialysis blood pressure, weight change, and Hb. Moreover, interdialytic weight gain, weight gain that occurs between dialysis sessions as a result of fluid accumulation, has been significantly associated with fatigue in dialysis patients. Partial results were reported by Kim and Son[11], in Korea, as they found a weak but significant correlation between PDF and intradialytic weight gain. This association indicates that weight gain may be one of the many contributors to PDF. Hypertension may be present in up to 80% of patients reaching end-stage renal disease[18], sometimes as a primary cause of renal failure but more usually as a secondary complication. In dialysis patients the commonly attributed to increased circulating intravascular volume, so-called volume-dependent hypertension, which is partially assessed by the interdialytic weight gain and controlled by fluid removal during dialysis to the appropriate dry weight. This practice assumes a direct relationship between weight gain and increased blood pressure, and indeed interdialytic weight gain has been directly related to cardiovascular mortality in HD patients[19]. Dialysis hypotension has a multifactorial etiology, including disparate causes such as autonomic, dysfunction, decreased plasma osmolality, and a decrease in extracellular fluid volume with inadequate plasma[20]. Levels of fatigue did not differ by physiological indicators except for anemia in the present study. It is not surprisingly that patients with high Hb levels have low fatigue levels. However, this situation is controversial and is not confirmed in all studies. Many studies investigating fatigue in HD patients have failed to show a relationship between Hb levels and fatigue[21]. However, several studies conducted with HD patients have indicated a relationship between a low level of Hb and fatigue[22],[23].

The current study showed that there was a significant relation between the studied groups regarding CRP. Partial results were found by Kutner et al.[23] who report that poor vitality was significantly related to both interleukin (IL)-6 and CRP. Moreover, Schindler et al.[24], reported that inflammatory markers like IL-1, IL-6, CRP, and TNFα have been studied extensively in cancer-related fatigue. In addition, Schubert et al.[25], found that high levels of CRP have also been shown to correlate with poor physical performance and muscle strength in myocardial infarction survivors and elderly people. Cesari et al.[26] showed that studies among patients with end-stage renal disease have also shown that elevated levels of proinflammatory cytokines are linked to an increase in energy expenditure, mortality, and lower functional status. The elevated levels of cytokines in HD patients are probably owing to the stress of uremia[28], and the dialytic treatment itself acts as a proinflammatory stimulus contributing to a further increase in cytokine secretion at the end of each session. In fact, the dialysis membrane itself can induce marked increases in the release of cytokines[24].

In the present study, the logistic regression analysis indicated that there were significant predictors for fatigue identified regarding female sex, number of children, hemoglobin, calcium, CRP, albumin, weight change, and predialysis SBP. Researchers [25-28] reported that the importance of fatigue in patients with kidney disease was emphasized by the observation that 94% of the patients who were undergoing HD endorsed a willingness to undergo more frequent dialysis if there was an associated increase in their energy level. Jhamb et al.[29] reported that fatigue influences individuals' role performance and functional status. At multivariate analysis, PDF was associated with weight change, predialysis DBP. Despite the importance of fatigue in patients, health care providers remain largely unaware of the presence and severity of fatigue in patients who undergo dialysis. Education programs for renal nurses should emphasize the importance of a holistic approach to care rather than overemphasizing technological aspects. Specific knowledge and skills to undertake assessment and provide care to deal with the range of PDF symptoms must be included. Such changes have the potential to enhance the quality of life for these patients.


  Conclusion Top


Our results concluded that excessive ultrafiltration, intradialytic hypotension, anemia, hypocalcemia, malnutrition, and C-reactive protein were statistically significant increase in PDF group compared with non-PDF. Moreover, there was a lack of correlation between TNFα and PDF. Finally, it is urgent to design adequate studies to understand the mechanism of PDF and, more importantly, develop effective therapeutic strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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