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Int J Biol Med Res.2023 ;14(4):7652-7654
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International Journal of Biological & Medical Research
International Journal of
BIOLOGICAL AND MEDICAL RESEARCH
www.biomedscidirect.com
Int J Biol Med Res
Volume 14, Issue 4, Oct 2023
Copyright 2023 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685. All rights reserved.
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ARTICLE INFO ABSTRACT
Keywords:
Interleukin-6
Chronic Kidney Disease
Inflammation, and Hemoglobin.
1. Introduction
Chronic Kidney Disease (CKD) is an irreversible loss of the
kidneyfunctionswhichisfatalintheabsenceofprescribeddialysis
or kidney transplant (1,2). Nowadays, there are increasing
evidences that associate CKD to the disruption in immune
responses. CKD affects over 800 million individual worldwide and
itisfastbecomingapublichealthconcernduetothehighmortality
and growing number of patients who required renal replacement
therapy (3). Numerous systemic and local insults, including
infections, hypoxemia, nephrotoxin, immune complexes
dysregulation, advanced glycation end products are known to
stimulate the kidney to produce systemic interleukin-6 (IL-6)
(4,5). Some studies (6,7) have reported high plasma IL-6 level in
CKDpatients.Interleukin-6acceleratestheprogressionofCKDnot
only by aggravating kidney injury as described above but also by
initiating its complications, especially the chronic vascular disease
(CVD).
MATERIALSANDMETHOD
StudydesignandPopulation
This was a cross-sectional laboratory-based study conducted
in August- September 2020 consisting of a control group of forty-
four apparently healthy participants, 27 (61.4%) were male, and a
test group of forty-four CKD patients, 17 (38.64%) were female,
provedbyhemodialysisinAlrebathospitalKhartoum,Sudan.
The study participants were recruited from the Alrebat
hospital Khartoum, Sudan. The apparently healthy volunteers for
the control without CKD, diabetes mellitus, hypertension, viral
infections (HIV, HBV, and HCV) or other knownrisk factors for CKD
were included for the study. Personal data was obtained by
standardquestionnairedesignedfordialysispatients.
Ethicalclearance
The study received ethical clearance from both the ethical
review committees at the Faculty of Medical Laboratory Science,
Sudan International University and Alrbat hospital, Khartoum,
Sudan. Inform consent was obtained from all the study
participants.
Background: High plasma interleukin-6 is common in chronic kidney disease patients due to
chronic stress, prolonged inflammation, and fluid overload. However, conflicting opinions still
exist. Moreover, the effects of age, sex, and ethnicity on interleukin-6 level in chronic kidney
disease is not known. Aim: This study aimed to determine interleukin-6 level in chronic kidney
diseasepatientsinKhartum,Sudan.Methods:Thisisacross-sectionallaboratorybasedstudy.A
total of 88 participants consisting of 44 chronic kidney disease patients and 44 apparently
healthy control. Of the 44 chronic kidney disease patients, 27 (61%) were male and 17 (39%)
female.Accordingtotheirage,15(34%)≤40yearsand29(66%)˃40yearsold.Concerningthe
duration of disease, 31 (70%) were ≤ 2 years and 13 (30%) were ˃ 2 years. Hemoglobin and
interleukin-6 concentration were determined using enzyme linked immunosorbent assay.
Results: Plasma interleukin -6 levels was significantly (p= 0.011) elevated in chronic kidney
disease(Mean±SD=51.72±9.63)comparedtocontrolgroup(Mean±SD=24.77±3.27).When
hemoglobin was considered, interleukin -6 correlates negatively with significant difference
(Correlation coefficient = -0.0364, p = 0.033). However, there was no statistical significant
difference among the sex, age, and duration of the disease.Conclusion: Interleukin -6 level was
significantly elevated in chronic kidney disease. There was no significant difference in the
interleukin -6 level among the sex, age, and duration of the disease. When hemoglobin was
considered,therewasanegativecorrelationwithinterleukin-6
Original article
Serum Interleukin - 6 level among Sudanese Patients with Chronic kidney disease
a a a a a b b
Safaa I.A Nasr , Rbab A.M Adam , Hala M.M Ibrahim , Afra S.A Abdelgadir , Ibrahim Alkider , Solomon M. Gamde , Simon P. Abriba
a
Department of Hematology and Immunohematology, Faculty of Medical Laboratory Science, Sudan International University.
b
Department of Medical Laboratory Science, Faculty of Health Sciences, Bingham University Karu, Nigeria
* Corresponding Author :
email; solomonmatthias85@gmail.com.
ORCID; http://orcid/0000-0002-7631-8782
Copyright 2023 BioMedSciDirect Publications IJBMR - All rights reserved.
c
Solomon Matthias Gamde
SamplePreparationandProcedure
On a 5 ml EDTA container, venous blood was collected by single
non traumatic venipuncture. Haemoglobin was measured by
automatic blood counter (Sysmex KX-21N) for both CKD patients
and control group. The centrifuged plasma was harvested into a
plain container for IL-6 estimation using enzyme linked
immunosorbentassay(ELISA).
PrincipleofEnzymeLinkedImmunosorbentAssay
This involves the reaction of an antibody with an antigen and a
detection system to determine if a reaction has occurred which
involve Binding of the test molecule or organism to a solid support
e.g.microtiterplate.
Statisticalanalysis
The data obtained were categorized into different groups and
analyzed by statistical using computer program statistical package
for social science (SPSS), used F- test (ANOVA) and T- test. Analyzed
datawasrepresentedintablesandfigures.
RESULT
Our data (Table 1) showed that IL-6 was significantly (p value
0.011) increased in CKD group (Mean±SD =51.72±9.63) compared
to control (Mean±SD=24.77±3.27). However, there was no statistical
significant (P ˃ 0.05) difference in IL-6 levels among the age groups,
gender,anddurationofthedisease(Table2).
The characteristics of the demographic data and mean
hemoglobin (Hb) concentration in CKD are given in Table 3. Hb Mean
± SD = 10.5±1.29, age group Mean ± SD = 46.5±13.7, and Mean ± SD =
1.97±0.74.
Figure 1 showed the percentages of the age groups, gender, and
durationofdisease.
In figure 2, hemoglobin correlates negatively with IL-6 level
(correlationcoefficient=-0.0364,Pvalue0.033).
DISCUSSION
Mortality due to CKD is a global problem due to high prevalence
ofCKDriskfactors.Thepresentstudyinvestigatedthepossibleeffect
of Interleukin (IL)-6 in CKD patients on hemodialysis. Our result
showed that the plasma IL-6 was significantly (P =0.011) elevated in
CKD patients (Mean±SD=51.72±9.63) compared to control
(Mean±SD=24.77±3.27). Our finding is in tandem with previous
studythatdocumentedinterleukin-6asaproinflammatoryandanti-
inflammatory cytokines which is elevated in chronic kidney disease
(10).Similarly,someclinicalandexperimentalstudieshavereported
that IL-6 enhanced the progression of CKD and its related
complications (10). Raised IL-6 expression in the urine of patients
with mesangial proliferative glomerulonephritis is often associated
with poor outcome (16). Moreover, high plasma IL-6 level is
commonly observed in CKD patients (6). It is evident from the
previousreportsthatIL-6levelissignificantlyhigherinCKDpatients
comparedwiththeapparentlyhealthygroup.
Furthermore,Interleukin-6enhancestheprogressionofCKDnot
only by inciting kidney damage as described above but also by
instigating its complications, particularly the chronic vascular
disease (CVD). Increasing evidences abound that IL-6 initiates
endothelial injury essentially by reducing endothelial nitric oxide
synthase and an anti-atherogenic adipocyte expression, and the
inoculation of recombinant IL-6 exacerbates atherosclerosis. These
mechanisms also suggests that IL-6 contributes to the increased
incidence of CVD in CKD patients. Nonetheless, the elevated plasma
IL-6 is not only a consequence of CKD, it also acts as a stimulant for
the progression of CKD and its related complications (17). However,
the present study is the first that demonstrated there was no
significant association in IL-6 among the age groups, gender, and
durationofthedisease.
CONCLUSION
Based on these finding, interleukin-6 level was significantly
raised in Chronic Kidney Disease. there was no significant
associationinIL-6amongtheagegroups,gender,anddurationofthe
disease. Our data also showed a negatively significant association
betweenHbandinterleukin-6levelinthestudypopulation.
ACKNOWLEDGEMENT
Our gratitude goes to the Staff in Alrebat Hospital who supported in
the sample collection and Khartoum University Institute of Endemic
Disease.
Conflictofinterest:Nonedeclared.
Funding:Nothingtodeclare
Figure 1: Percentages of the age groups, gender, and
duration of the disease
Figure2:CorrelationofIL-6andHblevelsinCKD
7653
Safaa I.A Nasr et al. /Int J Biol Med Res.14(4):7652-7654
Authors' Contribution: All authors were equally involved in data
collection, analysis, manuscript preparation, revision and
finalization.
7654
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All rights reserved.
Copyright 2023 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685.
c
Safaa I.A Nasr et al. /Int J Biol Med Res.14(4):7652-7654

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Serum interleukin - 6 level among sudanese patients with chronic kidney disease.pdf

  • 1. BioMedSciDirect Publications Int J Biol Med Res.2023 ;14(4):7652-7654 Contents lists available at BioMedSciDirect Publications Journal homepage: www.biomedscidirect.com International Journal of Biological & Medical Research International Journal of BIOLOGICAL AND MEDICAL RESEARCH www.biomedscidirect.com Int J Biol Med Res Volume 14, Issue 4, Oct 2023 Copyright 2023 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685. All rights reserved. c ARTICLE INFO ABSTRACT Keywords: Interleukin-6 Chronic Kidney Disease Inflammation, and Hemoglobin. 1. Introduction Chronic Kidney Disease (CKD) is an irreversible loss of the kidneyfunctionswhichisfatalintheabsenceofprescribeddialysis or kidney transplant (1,2). Nowadays, there are increasing evidences that associate CKD to the disruption in immune responses. CKD affects over 800 million individual worldwide and itisfastbecomingapublichealthconcernduetothehighmortality and growing number of patients who required renal replacement therapy (3). Numerous systemic and local insults, including infections, hypoxemia, nephrotoxin, immune complexes dysregulation, advanced glycation end products are known to stimulate the kidney to produce systemic interleukin-6 (IL-6) (4,5). Some studies (6,7) have reported high plasma IL-6 level in CKDpatients.Interleukin-6acceleratestheprogressionofCKDnot only by aggravating kidney injury as described above but also by initiating its complications, especially the chronic vascular disease (CVD). MATERIALSANDMETHOD StudydesignandPopulation This was a cross-sectional laboratory-based study conducted in August- September 2020 consisting of a control group of forty- four apparently healthy participants, 27 (61.4%) were male, and a test group of forty-four CKD patients, 17 (38.64%) were female, provedbyhemodialysisinAlrebathospitalKhartoum,Sudan. The study participants were recruited from the Alrebat hospital Khartoum, Sudan. The apparently healthy volunteers for the control without CKD, diabetes mellitus, hypertension, viral infections (HIV, HBV, and HCV) or other knownrisk factors for CKD were included for the study. Personal data was obtained by standardquestionnairedesignedfordialysispatients. Ethicalclearance The study received ethical clearance from both the ethical review committees at the Faculty of Medical Laboratory Science, Sudan International University and Alrbat hospital, Khartoum, Sudan. Inform consent was obtained from all the study participants. Background: High plasma interleukin-6 is common in chronic kidney disease patients due to chronic stress, prolonged inflammation, and fluid overload. However, conflicting opinions still exist. Moreover, the effects of age, sex, and ethnicity on interleukin-6 level in chronic kidney disease is not known. Aim: This study aimed to determine interleukin-6 level in chronic kidney diseasepatientsinKhartum,Sudan.Methods:Thisisacross-sectionallaboratorybasedstudy.A total of 88 participants consisting of 44 chronic kidney disease patients and 44 apparently healthy control. Of the 44 chronic kidney disease patients, 27 (61%) were male and 17 (39%) female.Accordingtotheirage,15(34%)≤40yearsand29(66%)˃40yearsold.Concerningthe duration of disease, 31 (70%) were ≤ 2 years and 13 (30%) were ˃ 2 years. Hemoglobin and interleukin-6 concentration were determined using enzyme linked immunosorbent assay. Results: Plasma interleukin -6 levels was significantly (p= 0.011) elevated in chronic kidney disease(Mean±SD=51.72±9.63)comparedtocontrolgroup(Mean±SD=24.77±3.27).When hemoglobin was considered, interleukin -6 correlates negatively with significant difference (Correlation coefficient = -0.0364, p = 0.033). However, there was no statistical significant difference among the sex, age, and duration of the disease.Conclusion: Interleukin -6 level was significantly elevated in chronic kidney disease. There was no significant difference in the interleukin -6 level among the sex, age, and duration of the disease. When hemoglobin was considered,therewasanegativecorrelationwithinterleukin-6 Original article Serum Interleukin - 6 level among Sudanese Patients with Chronic kidney disease a a a a a b b Safaa I.A Nasr , Rbab A.M Adam , Hala M.M Ibrahim , Afra S.A Abdelgadir , Ibrahim Alkider , Solomon M. Gamde , Simon P. Abriba a Department of Hematology and Immunohematology, Faculty of Medical Laboratory Science, Sudan International University. b Department of Medical Laboratory Science, Faculty of Health Sciences, Bingham University Karu, Nigeria * Corresponding Author : email; solomonmatthias85@gmail.com. ORCID; http://orcid/0000-0002-7631-8782 Copyright 2023 BioMedSciDirect Publications IJBMR - All rights reserved. c Solomon Matthias Gamde
  • 2. SamplePreparationandProcedure On a 5 ml EDTA container, venous blood was collected by single non traumatic venipuncture. Haemoglobin was measured by automatic blood counter (Sysmex KX-21N) for both CKD patients and control group. The centrifuged plasma was harvested into a plain container for IL-6 estimation using enzyme linked immunosorbentassay(ELISA). PrincipleofEnzymeLinkedImmunosorbentAssay This involves the reaction of an antibody with an antigen and a detection system to determine if a reaction has occurred which involve Binding of the test molecule or organism to a solid support e.g.microtiterplate. Statisticalanalysis The data obtained were categorized into different groups and analyzed by statistical using computer program statistical package for social science (SPSS), used F- test (ANOVA) and T- test. Analyzed datawasrepresentedintablesandfigures. RESULT Our data (Table 1) showed that IL-6 was significantly (p value 0.011) increased in CKD group (Mean±SD =51.72±9.63) compared to control (Mean±SD=24.77±3.27). However, there was no statistical significant (P ˃ 0.05) difference in IL-6 levels among the age groups, gender,anddurationofthedisease(Table2). The characteristics of the demographic data and mean hemoglobin (Hb) concentration in CKD are given in Table 3. Hb Mean ± SD = 10.5±1.29, age group Mean ± SD = 46.5±13.7, and Mean ± SD = 1.97±0.74. Figure 1 showed the percentages of the age groups, gender, and durationofdisease. In figure 2, hemoglobin correlates negatively with IL-6 level (correlationcoefficient=-0.0364,Pvalue0.033). DISCUSSION Mortality due to CKD is a global problem due to high prevalence ofCKDriskfactors.Thepresentstudyinvestigatedthepossibleeffect of Interleukin (IL)-6 in CKD patients on hemodialysis. Our result showed that the plasma IL-6 was significantly (P =0.011) elevated in CKD patients (Mean±SD=51.72±9.63) compared to control (Mean±SD=24.77±3.27). Our finding is in tandem with previous studythatdocumentedinterleukin-6asaproinflammatoryandanti- inflammatory cytokines which is elevated in chronic kidney disease (10).Similarly,someclinicalandexperimentalstudieshavereported that IL-6 enhanced the progression of CKD and its related complications (10). Raised IL-6 expression in the urine of patients with mesangial proliferative glomerulonephritis is often associated with poor outcome (16). Moreover, high plasma IL-6 level is commonly observed in CKD patients (6). It is evident from the previousreportsthatIL-6levelissignificantlyhigherinCKDpatients comparedwiththeapparentlyhealthygroup. Furthermore,Interleukin-6enhancestheprogressionofCKDnot only by inciting kidney damage as described above but also by instigating its complications, particularly the chronic vascular disease (CVD). Increasing evidences abound that IL-6 initiates endothelial injury essentially by reducing endothelial nitric oxide synthase and an anti-atherogenic adipocyte expression, and the inoculation of recombinant IL-6 exacerbates atherosclerosis. These mechanisms also suggests that IL-6 contributes to the increased incidence of CVD in CKD patients. Nonetheless, the elevated plasma IL-6 is not only a consequence of CKD, it also acts as a stimulant for the progression of CKD and its related complications (17). However, the present study is the first that demonstrated there was no significant association in IL-6 among the age groups, gender, and durationofthedisease. CONCLUSION Based on these finding, interleukin-6 level was significantly raised in Chronic Kidney Disease. there was no significant associationinIL-6amongtheagegroups,gender,anddurationofthe disease. Our data also showed a negatively significant association betweenHbandinterleukin-6levelinthestudypopulation. ACKNOWLEDGEMENT Our gratitude goes to the Staff in Alrebat Hospital who supported in the sample collection and Khartoum University Institute of Endemic Disease. Conflictofinterest:Nonedeclared. Funding:Nothingtodeclare Figure 1: Percentages of the age groups, gender, and duration of the disease Figure2:CorrelationofIL-6andHblevelsinCKD 7653 Safaa I.A Nasr et al. /Int J Biol Med Res.14(4):7652-7654
  • 3. Authors' Contribution: All authors were equally involved in data collection, analysis, manuscript preparation, revision and finalization. 7654 References 1. National Insttitute of Diabetes and Digestive and Kidney Diseases ''Kidney Failure''.Retrieved11November, 2017. 2. ”What is renal failure?”. Johns Hopkins Medicine. Archived from the original on18June2017.Retrieved18December,2017. 3. Marwa Osman, Mazin Shigidi, Haider Ahmed, Ihab Abdelrahman, Wieam Karrar, Elhussein Elhassan, Hussam Shwaib, Rayyan Ibrahim, Marwa Abdalla. Pattern and outcome of acute kidney injury among Sudanese adults admittedtoatertiarylevelhospital:aretrospectivecohortstudy.PanAfrican MedicalJournal.2017;28:90:1-7.doi:10.11604/pamj.2017.28.90.11054 4. Su H, Lei C-T and Zhang C. Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front. Immunol. 2017: 8:405. doi: 10.3389/fimmu.2017.00405. 5 .Yung S, Tsang RC, Sun Y, Leung JK, Chan TM. Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis. J Am Soc Nephrol,2005;16:3281–94.doi:10.1681/ASN.2004110917. 6. Pecoits-Filho R, Heimburger O, Barany P, Suliman M, Fehrman-Ekholm I, Lindholm B, et al. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis, 2003: 41:1212–8.Doi:10.1016/S0272-6386(03)00353-6. 7. Akhtar Atiya, Taghreed Majrashi, Safia Akhtar, Arshad Ali Khan ,Afnan Mohammad Sultan Asiri, Hanan Jamaan Al-Zahrania, Raghad Sameer Alnami, Sara Abdulrahman Alsharif, Taef Amer, Zainah Abdullah Faiz, ShimaaAhmadMAlYahya,ShahadSaeedhabtar.ThevalueofGenusAcaciain arid and semi-arid environments for the treatment of chronic inflammatory d i s e a s e s . . P h y t o m e d i c i n e P l u s 2 ; 2 0 2 2 : 1 0 0 3 1 5 . https://doi.org/10.1016/j.phyplu.2022.100315.1-39. 8. . Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, et al. Regulationofadiponectinbyadiposetissue-derivedcytokines:invivoandin vitro investigations in humans. Am J Physiol Endocrinol Metab, 2003: 285:E527–33.doi:10.1152/ajpendo.00110.2003. 9. Huber SA, Sakkinen P, Conze D, Hardin N, and Tracy R. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol, 1999;19:2364–7.doi:10.1161/01.ATV.19.10.2364. 10. Amdur, R.L. et al. interleukin-6 is arisk factor for atrial fibrillation in chronic kidney disease: findings from the CRIC study. PLOS ONE, 2016. http://dx.doi.org/doi:10.1371/journal.pone.0148189. 11. Takahashi T, Kubota M, Nakamura T, Ebihara I, Koide H. Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail , 2000; 22:345–54.Doi:10.1081/JDI-100100878. 12. Caglar K, Peng Y, Pupim LB, Flakoll PJ, Levenhagen D, Hakim RM, et al. Inflammatory signals associated with hemodialysis. Kidney Int, 2002; 62:1408–16.doi:10.1111/j.1523-1755.2002.kid556.x. 13. Ranganathan P, Jayakumar C, Ramesh G. Proximal tubule-specific overexpression of netrin-1 suppresses acute kidney injury-induced interstitial fibrosis and glomerulosclerosis through suppression of IL- 6/STAT3 signaling. Am J Physiol Renal Physiol, 2013; 304:F1054–65. Doi: 10.1152/ajprenal.00650.2012. 14. KielarML,JohnR,BennettM,RichardsonJA,SheltonJM,ChenL.Maladaptive role of IL-6 in ischemic acute renal failure. J Am Soc Nephrol, 2005; 16:3315–25.doi:10.1681/ASN.2003090757 15. Harcourt BE, Forbes JM, Matthews VB. Obesity-induced renal impairment is exacerbated in interleukin-6-knockout mice. Nephrology (Carlton), 2012; 17:257–62.doi:10.1111/j.1440-1797.2011.01547.x. 16. Nephrology Dialysis Transplantation, 2015 30(4): 564–574, https://doi.org/10.1093/ndt/gfu233(2014). 17. Su H, Lei C-T and Zhang C (2017) Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front. Immunol. 8:405. doi: 10.3389/fimmu.2017.00405. All rights reserved. Copyright 2023 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685. c Safaa I.A Nasr et al. /Int J Biol Med Res.14(4):7652-7654