[Muhar* et al.

, 7(1): January, 2020] ISSN: 2349-5197

Impact Factor: 3.765

INTERNATIONAL JOURNAL OF RESEARCH SCIENCE & MANAGEMENT

CORRELATION BETWEEN QUALITY OF LIFE WITH INTERLEUKIN-6 SERUM
LEVELS INCHRONIC KIDNEY DISEASE PATIENTS UNDERGOING REGULAR
HEMODIALYSIS
Ahmad Muhar*, Habibah Hanum Nasution & Alwi Thamrin Nasution

DOI: 10.5281/zenodo.3612085

Abstract
The morbidity and mortality rates of patients with chronic kidney disease (CKD), who undergo regular
hemodialysis are still high. Cytokine levels, such as IL-1, IL-6, and TNF-α are often found to be increased in
hemodialysis patients. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) has been
widely used in evaluating the quality of life of patients suffering from chronic diseases. This study aims to
determine the level of quality of life and serum interleukin-6 levels in regular hemodialysis patients. This study
was an observational cross-sectional method which was carried out at the hemodialysis center at the General
Hospital. H. Adam Malik (RSUP HAM) during February - April 2017 with a sample of 45 people who were
collected consecutively. Samples were patients with chronic kidney failure who had undergone regular
hemodialysis at RSUP HAM. The majority of subjects causing chronic kidney disease were hypertensive
nephropathy in 25 patients (55.6%). Serum IL-6 laboratory examination showed a mean value of 9.02. Based on
our SF-36 questionnaire, we found a mean value below 50 for all scales examined in the study samples.
Spearman correlation test between IL-6 with each scale from the SF-36 questionnaire found all parameters
produced positive correlation data (p <0.05). We conclude that there is a significant correlation between IL-6
levels and the quality of life of Chronic Kidney Disease patients undergoing hemodialysis.

Keywords: Chronic Kidney Disease, Hemodialysis, Interleukin-6. SF-36 Questionnaire.

Introduction
CKD is a pathophysiological process with various etiologies, resulting in a progressive decline in kidney
function, which generally ends with kidney failure. The morbidity and mortality rates of CKD patients, who
undergo regular hemodialysis are still high, ranging from 15-20% per year, although improvement in
management of cardiovascular disease, infection and dialysis therapy has been carried out (1).

CKD is a pathophysiological process with various etiologies, resulting in a progressive decline in kidney
function, which generally ends with kidney failure. The morbidity and mortality rates of CKD patients, who
undergo regular hemodialysis are still high, ranging from 15-20% per year, although improvement in
management of cardiovascular disease, infection and dialysis therapy has been carried out (2,3).

SF-36 is one instrument that has been proven to be used to assess quality of life in almost all chronic disease
studies including hemodialysis patients and can also be used to assess quality of life in healthy populations. This
instrument is simple and easy and is widely used (3,4).

Interleukin-6 (IL-6) has the most important role in the production of most acute phase proteins, whereas other
cytokines affect the acute phase protein subgroup. IL-6 is a multifunctional cytokine that plays a role in the
regulation of inflammation, immune response, acute phase reactants and hematopoiesis, exerting its effects on
local and systemic tissue (4).

About 30-50% of predialysis patients, hemodialysis (HD) has elevated serum levels of inflammatory markers.
Nevertheless, the high trend in the distribution of inflammatory markers that are often used such as C-Reactive
Protein (CRP) and interleukin-6 (IL-6) indicates patient-specific processes. Epidemiologic data significantly
show that plasma IL-6 is associated with cardiovascular morbidity and mortality in non-renal patients. In CKD
patients an increase in IL-6 levels is a strong predictor of poor outcome(1,4).

http: // [Link] © International Journal of Research Science & Management

[68]
[Muhar* et al., 7(1): January, 2020] ISSN: 2349-5197
Impact Factor: 3.765

INTERNATIONAL JOURNAL OF RESEARCH SCIENCE & MANAGEMENT

n this study trying to link the inflammatory factor (IL-6) with quality of life (as assessed using the SF-36
questionnaire) CKD patients undergoing routine hemodialysis.

Research methods

Sampling method
This research is observational with cross sectional method. The study was conducted at the H. Adam Malik
General Hospital Medan throughout February - April 2017. The sample collection was carried out using the
consecutive method with a total sample of 45 people. Criteria for inclusion of samples were male or female
patients, aged> 18 years, and kidney failure patients who underwent hemodialysis for> 3 months with stable
conditions. Patients involved in the study were asked for oral and written consent by signing an informed
consent sheet. This study was approved by the Local Health Research Ethics Committee.

Data Analysis
Data samples were taken based on the results of history taking, physical examination (vital signs and
anthropometry), laboratory results as well as patient questionnaire results. Examination of blood samples using
the Human Interleukin-6 Immunoassay (R&D System) method to obtain the value of interleukin-6. During the
hemodialysis process, patients were also asked to fill out the SF-36 questionnaire. The data will be analyzed by
Pearson correlation test if normally distributed or Spearman correlation test if not normally distributed using
SPSS 22.0. A p value <0.05 (95%) was considered statistically significant.

Results
We found that the majority of samples experiencing CKD were caused by hypertensive nephropathy (55.6%),
age> 40 years (82.2%), and working as an entrepreneur (48.9%). Serum IL-6 laboratory examination showed a
mean value of 9.02. From the examination using the SF-36 questionnaire, we obtained a mean score below 50
for all scales examined (table 1).

Table 1. Characteristics of Subjects

Characteristics n = 45
Gender
Male 29 (64.4%)
Female 16 (35.6%)
Age (>40 years) 37 (82.2%)
Occupation
Enterpreneur 25 (48.9%)
Civil Servant 8 (17.8%)
Housewife 10 (22.2%)
Pension 5 (11.1%)
Diagnosis
Hypertensive Nephropathy 25 (55.6%)
Diabetic Nephropathy 11 (24.4%)
Obstructive Kidney Disease 6 (13.3%)
Chronic Glomerulonephritis 3 (6.7%)
IL-6 Serum (Mean) 9.02
SF-36 Components
SF-36 Physical Functions 41.96
SF-36 limitations due to 32.8
emotional problems
SF-36 Mental Health 43.22
SF-36 Social Functions 44.56
SF-36 limitations due to 30.29
physical problems

http: // [Link] © International Journal of Research Science & Management

[69]
[Muhar* et al., 7(1): January, 2020] ISSN: 2349-5197
Impact Factor: 3.765

INTERNATIONAL JOURNAL OF RESEARCH SCIENCE & MANAGEMENT

SF-36 feeling sick 46.51
SF-36 general health 27.89
SF-36 energy 31.89

The distribution of IL-6 data and scores for the entire SF-36 scale were not normally distributed so we used the
Spearman correlation test to conduct correlation tests between IL-6 and each scale from the SF-36
questionnaire. We found that all parameters produced negative correlation data so it was concluded that there
was a significant negative correlation between IL-6 and the SF-36 scale component (table 2).

Discussion
From our research, we found that in patients undergoing regular hemodialysis, there was a mean IL-6 serum
level which was quite high (9.02 pg/mL). This is in accordance with research conducted by Bosolla, et al. which
states that serum IL-6 levels are higher in the group experiencing fatigue due to chronic hemodialysis (5.1 + 3.4
SD) than the group without fatigue (1,6 + 1,5 SD) (P <0,001) (5).

Research conducted by Barreto et al. also states that plasma IL-6 levels significantly increase in advanced-stage
CKD and independently predict mortality when compared with three other acute phase proteins (CRP, TNF-α,
and albumin) (6).

In this study, we also obtained a low SF-36 value in patients undergoing regular hemodialysis which means a
decrease in the quality of life of patients. The SF-36 value for each parameter in this study is in the range of
27.89 - 46.51. This is consistent with research conducted by Rambod, et al. which states that there is a strong
association for several physical health components of SF-36 compared to mental health components in patients
undergoing dialysis. Research conducted by Crus, et al also stated that the mean SF-36 value in CKD patients
undergoing hemodialysis was below 70 in most questionnaire parameters(7,8).

Table 2. Spearman Correlation Test Results

IL-6
Parameter
Nilai Korelasi Spearman P-Value
SF-36 fungsi fisik -0.361 0.015
SF-36 keterbatasan akibat masalah emosional -0.298 0.047
SF-36 kesehatan mental -0.359 0.015
SF-36 fungsi sosial -0.382 0.010
SF-36 keterbatasan akibat masalah fisik -0.319 0.033
SF-36 perasaaan sakit -0.367 0.013
SF-36 kesehatan umum -0.325 0.029
SF-36 energi -0.313 0.036

In most studies, normal healthy populations usually have values above this level (7,8).

These results contradict research conducted by Jhamb, et al. which states that the SF-36 vitality scale may fail to
fully predict people with more severe fatigue in patients undergoing dialysis (9).This difference is likely due to
the subjectivity factor of the implementer who assessed the SF-36 instrument.

In this study a positive correlation was found between an increase in IL-6 and a low SF-36 value in all
parameters (P <0.05). This is in line with research conducted by Cruz, et al and Germin-Petrovi et al. which
states that there is a negative impact on the quality of life of patients in the early stages of CKD, although we
cannot detect a significant relationship between the stage of the disease and the components of the SF-36
questionnaire (10,11,12).

http: // [Link] © International Journal of Research Science & Management

[70]
[Muhar* et al., 7(1): January, 2020] ISSN: 2349-5197
Impact Factor: 3.765

INTERNATIONAL JOURNAL OF RESEARCH SCIENCE & MANAGEMENT

However, research by M. Artom et al found that the SF-36 vitality subscale failed to reflect several aspects of
fatigue, such as lack of motivation and weakness. Research conducted by Feroze, et al. also mentioned that there
was no significant correlation between SF-36 and inflammatory mediators, such as IL-6 (13,14). More in-depth
studies and further research on these differences must be carried out so that the causes of these differences can
be found.

Conclusion
There is a significant correlation between IL-6 levels and patients undergoing hemodialysis. An increase in IL-6
levels also has a negative correlation with a decrease in SF-36, which indicates an increasingly high level of
fatigue and a decrease in the quality of life of patients. Based on this, the SF-36 questionnaire can be used as an
instrument to predict quality of life in patients undergoing regular hemodialysis.

References
[1] URSDS. 2010. The United Renal Data System. Overall hospitalization and mortality. AM J Kidney
Dis,55(1):S1-A7
[2] Mittal SK, Ahern L, Flaster E, Maesaka JK, Fisbane S. Self-assessed physical and mental function of
haemodialysis patients. Nephrol Dial Transplant 2001; 16:1387-94.
[3] Rand. How to score the Rand SF-36 Questionnaire.
[4] Zadeh KK, Kopple JD, Block G, Humphreys MH. 2001. Association Among SF36 Quality of Life
Measures and Nutrition, Hospitalization and Mortality in Hemodialysis. J of the American Society of
Nephrology, 12: 2797- 806.
[5] Maurizio Bossola, Enrico Di Stasio, Stefania Giungi, dkk. Fatigue Is Associated With Serum Interleukin-
6 Levels and Symptoms of Depression in Patients on Chronic Hemodialysis. J Pain Symptom Manage
2015;49:578e585.
[6] Daniela V. Barreto, Fellype C. Barreto Sophie Liabeuf, dkk. Plasma interleukin-6 is independently
associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease.
Kidney International (2010) 77, 550–556.
[7] Mehdi Rambod, Csaba P Kovesdy, Rachelle Bross, Joel D Kopple, dan Kamyar Kalantar-Zadeh.
Association of serum prealbumin and its changes over time with clinical outcomes and survival in
patients receiving hemodialysis. Am J Clin Nutr 2008;88:1485–94.
[8] Liang-Jen Wang, dan Chih-Ken Chen. The Psychological Impact of Hemodialysis on Patients with
Chronic Renal Failure. InTech 2010.
[9] Manisha Jhamb, Francis Pike, Sarah Ramer, dkk. Impact of Fatigue on Outcomes in the Hemodialysis
(HEMO) Study. Am J Nephrol 2011;33:515–523.
[10] Maria Carolina Cruz, Carolina Andrade, Milton Urrutia, dkk. Quality of life in patients with chronic
kidney disease. Clinics 2011;66(6):991-995.
[11] Daniela Germin-Petrovi, Iva Mesaro, dan Ana Lesac. Health-related Quality of Life in the Patients on
Maintenance Hemodialysis: The Analysis of Demographic and Clinical Factors. Coll. Antropol. 35
(2011) 3: 687–693.
[12] Ewa Baum, Krzysztof Pawlacz, dan Beata Maćkowiak. Levels of hepatocyte growth factor in serum
correlate with quality of life in hemodialysis patients. Int J Clin Exp Pathol 2015;8(10):13477-13482.
[13] Micol Artom, Rona Moss-Morris, Fergus Caskey, dan Joseph Chilcot. Fatigue in advanced kidney
disease. Kidney International (2014) 86, 497–505.
[14] Jhamb M, Weisbord SD, Steel JL, Unruh M. Fatigue in patients receiving maintenance dialysis: a review
of definitions, measures, and contributing factors. Am J Kidney Dis 2008; 52: 353–365.

http: // [Link] © International Journal of Research Science & Management

[71]