The Correlation of Interleukin-6, Malnutrition Inflammation Score and Asymmetric Dimethylarginine in Chronic Kidney Disease Patients Undergoing Routine Hemodialysis
DOI:
https://doi.org/10.3889/oamjms.2022.10626Keywords:
Interleukin-6, Malnutrition inflammation score, Asymmetric dimethylarginine, Chronic kidney disease, HemodialysisAbstract
Introduction: Chronic kidney disease (CKD) patients undergoing routine hemodialysis (HD) have a high prevalence of protein-energy malnutrition (PEM) and inflammation. The combination of inflammation and PEM is associated with cardiovascular disease and poor outcomes. Interleukin-6 (IL-6) is an inflammatory factor that runs parallel to endothelial damage and is closely related to the nutritional status of CKD HD patients. The tool to assess nutrition status is Malnutrition Inflammation Score (MIS) and to assess endothelial damage is Asymmetric Dimethylarginine (ADMA). It is currently unclear whether there is a correlation between inflammation, malnutrition, and endothelial dysfunction. Therefore the aim of this study is to determine the correlation between IL-6, MIS and ADMA in CKD HD patients.
Methods: A cross-sectional design with analytic observational study was conducted on end stage renal disease patient who undergo routine hemodialysis for at least 2 years with the duration of hemodialysis is 4-5 hours and at least twice per week. IL-6 was examined by kit (ELISA) and ADMA using LC-MS/MS at a certified laboratory in Manado city. History taking and physical examination were used to calculate MIS. Data analysis was done using SPSS version 22.
Results: There were 30 participants consisting of 22 men (72%) and 8 women (28%). The median age of the subjects was 56.50 years. There was a statistically significant positive correlation between IL-6 and ADMA (r = 0.440, p = 0.015), MIS and ADMA (r = 0.378, p = 0.039), and IL-6 and MIS (r = 0.682, p = 0.0001).
Conclusion: There was a significant correlation between IL-6, MIS and ADMA.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Luyckx VA, Stanifer JW, Tonelli M. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ. 2018;96(6)414-22D. https://doi.org/10.2471/BLT.17.206441 PMid:29904224 DOI: https://doi.org/10.2471/BLT.17.206441
Hilmanto D, Mawardi F, Lestari AS, Widiasta A. Disease-associated systemic complications in childhood nephrotic syndrome: A systematic review. Int J Nephrol Renovasc Dis. 2022;15:53-62. https://doi.org/10.2147/IJNRD.S351053 PMid:35241925 DOI: https://doi.org/10.2147/IJNRD.S351053
Widiasta A, Pardede SO, Rachmadi D. Correlation between LDL, HDL, total cholesterol, and triglyceride with the degree of chronic kidney disease in children. Am J Clin Med Res. 2017;5(1):1-5. https://doi.org/10.12691/ajcmr-5-1-1
As’Habi A, Tabibi H, Hedayati M, Mahdavi-Mazdeh M, Nozary- Heshmati B. Association of malnutrition-inflammation score, dialysis-malnutrition score and serum albumin with novel risk factors for cardiovascular diseases in hemodialysis patients. Ren Fail. 2015;37(1):113-6. https://doi.org/10.3109/0886022X.2014.967615 PMid:25296104 DOI: https://doi.org/10.3109/0886022X.2014.967615
Stenvinkel P, Barany P, Heimbur̈ger O, Pecoits-Filho R, Lindholm B. Mortality, malnutrition, and atherosclerosis in ESRD: What is the role of interleukin-6? Kidney Int Suppl. 2002;61(80):103-8. https://doi.org/10.1046/j.1523-1755.61.s80.19.x PMid:11982823 DOI: https://doi.org/10.1046/j.1523-1755.61.s80.19.x
Rao P, Reddy GC, Kanagasabapathy AS. Malnutrition-inflammation-atherosclerosis syndrome in chronic kidney disease. Indian J Clin Biochem. 2008;23(3):209-17. https://doi.org/10.1007/s12291-008-0048-9 PMid:23105756 DOI: https://doi.org/10.1007/s12291-008-0048-9
Roumeliotis S, Mallamaci F, Zoccali C. Endothelial dysfunction in chronic kidney disease, from biology to clinical outcomes: A 2020 update. J Clin Med. 2020;9(8):2359. https://doi.org/10.3390/jcm9082359 DOI: https://doi.org/10.3390/jcm9082359
Tripepi G, Raso FM, Sijbrands E, Seck MS, Maas R, Boger R, et al. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011;6(7):1714-21. https://doi.org/10.2215/CJN.11291210 PMid:21642364 DOI: https://doi.org/10.2215/CJN.11291210
Didion SP. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. Int J Mol Sci. 2017;18(12):2563. https://doi.org/10.3390/ijms18122563 PMid:29186034 DOI: https://doi.org/10.3390/ijms18122563
Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis. 2001;38(6):1251-63. https://doi.org/10.1053/ajkd.2001.29222 PMid:11728958 DOI: https://doi.org/10.1053/ajkd.2001.29222
Rambod M, Bross R, Zitterkoph J, Benner D, Pithia J, Colman S, et al. Association of malnutrition-inflammation score with quality of life and mortality in maintenance hemodialysis patients: A 5--year prospective cohort study. Am J Kidney Dis. 2008;53(2):289-309. https://doi.org/10.1053/j.ajkd.2008.09.018 PMid:19070949 DOI: https://doi.org/10.1053/j.ajkd.2008.09.018
Aditia K, Palar S, Karema-Kaparang AM, Moeis ES, Sugeng C, Umboh O. POS-552 correlation of interleukin-6 levels, high sensitivity c-reactive protein, and malnutrition inflammation score with quality of life chronic kidney disease patients undergoing routine hemodialysis. Kidney Int Rep. 2022;7(2):S239. https://doi.org/10.1016/j.ekir.2022.01.584 DOI: https://doi.org/10.1016/j.ekir.2022.01.584
Lopes AA. The malnutrition-inflammation score: A valid nutritional tool to assess mortality risk in kidney transplant patients. Am J Kidney Dis. 2011;58(1):7-9. https://doi.org/10.1053/j.ajkd.2011.04.003 PMid:21684436 DOI: https://doi.org/10.1053/j.ajkd.2011.04.003
González-Ortiz AJ, Arce-Santander CV, Vega-Vega O, Correa-Rotter R, Espinosa-Cuevas MD. Assessment of the reliability and consistency of the “malnutrition inflammation score” (MIS) in Mexican adults with chronic kidney disease for diagnosis of protein-energy wasting syndrome (PEW). Nutr Hosp. 2014;31(3):1352-8. https://doi.org/10.3305/nh.2015.31.3.8173 PMid:25726233
Aggarwal HK, Jain D, Chauda R, Bhatia S, Sehgal R. Assessment of malnutrition inflammation score in different stages of chronic kidney disease. Pril (Makedon Akad Nauk Umet Odd Med Nauki. 2018;39(2-3):51-61. https://doi.org/10.2478/prilozi-2018-0042 PMid:30864357 DOI: https://doi.org/10.2478/prilozi-2018-0042
ADMA/SDMA. United States of America: Cleveland HeartLab, Inc.; 2015. Available from: https://www.clevelandheartlab.com/tests/adma-sdma [Last accessed on 2022 Jan 02].
Indonesian Renal Registry. 11th Report of Indonesian Renal Registry. Perkumpulan Nefrologi Indonesia, Indones. Ren. Regist. (2018) 1-46
Ho L, Wang HH, Peng YS, Chiang CK, Huang JW, Hung KY, et al. Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: Focus on identifying the best cut-off point. Am J Nephrol. 2008;28(5):840-6. https://doi.org/10.1159/000137684 PMid:18535370 DOI: https://doi.org/10.1159/000137684
Oner-Iyidogan Y, Oner P, Kocak H, Gurdol F, Bekpinar S, Unlucerci Y, et al. Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis. Clin Exp Med. 2009;9:235-41. https://doi.org/10.1007/s10238-009-0035-3 PMid:19238516 DOI: https://doi.org/10.1007/s10238-009-0035-3
Kaizu Y, Kimura M, Yoneyama T, Miyaji K, Hibi I, Kumagai H. Interleukin-6 may mediate malnutrition in chronic hemodialysis patients. Am J Kidney Dis. 1998;31(1):93-100. https://doi.org/10.1053/ajkd.1998.v31.pm9428458 PMid:9428458 DOI: https://doi.org/10.1053/ajkd.1998.v31.pm9428458
Kato A, Odamaki M, Takita T, Maruyama Y, Kumagai H, Hishida A. Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients. Kidney Int. 2002;61(3):1143-52. https://doi.org/10.1046/j.1523-1755.2002.00215.x PMid:11849469 DOI: https://doi.org/10.1046/j.1523-1755.2002.00215.x
Muzasti RA, Hariman H, Daulay ER. Interleukin 6 concentration elevation as a risk of carotid intimamedia thickness in chronic kidney disease patients with dialysis. Med Glas (Zenica). 2020;17(2):346-51. https://doi.org/10.17392/1172-20 PMid:32662610
Kalantar-Zadeh K, Kopple JD, Humphreys MH, Block G. Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients. Nephrol Dial Transplant. 2004;19(6):1507-19. https://doi.org/10.1093/ndt/gfh143 PMid:15069177 DOI: https://doi.org/10.1093/ndt/gfh143
Thandavan T, Abraham G, Soundararajan P, Chandrasekaran V. Interleukin 6 strongly correlates with malnutrition inflammation score and it is strong predictor for mortality in hemodialysis patients. Urol Nephrol Open Access J. 2015;2(2):40-2. https://doi.org/10.15406/unoaj.2015.02.00030 DOI: https://doi.org/10.15406/unoaj.2015.02.00030
Herbelin A, Ureña P, Nguyen AT, Zingraff J, Descamps-Latscha B. Elevated circulating levels of interleukin-6 in patients with chronic renal failure. Kidney Int. 1991;39(5):954-60. https:// doi.org/10.1038/ki.1991.120 PMid:2067212 DOI: https://doi.org/10.1038/ki.1991.120
Jofré R, Rodriguez-Benitez P, López-Gómez JM, Pérez-Garcia R. Inflammatory syndrome in patients on hemodialysis. J Am Soc Nephrol. 2006;17(12 Suppl 3):S274-80. https://doi.org/10.1681/ASN.2006080926 PMid:17130274 DOI: https://doi.org/10.1681/ASN.2006080926
Pecoits-Filho R, Lindholm B, Axelsson J, Stenvinkel P. Update on interleukin-6 and its role in chronic renal failure. Nephrol Dial Transplant. 2003;18(6):1042-5. https://doi.org/10.1093/ndt/gfg111 PMid:12748331 DOI: https://doi.org/10.1093/ndt/gfg111
Małgorzewicz S, Heleniak Z, Lichodziejewska-Niemierko M, Rutkowski R, Aleksandrowicz-Wrona E, Dębska-Ślizień A. Protein-energy wasting and asymmetric dimethylarginine in peritoneal dialysis patients. Acta Biochim Pol. 2018;65(4):581-4. https://doi.org/10.18388/abp.2018_2634 PMid:30508418 DOI: https://doi.org/10.18388/abp.2018_2634
Nakahama H, Tanaka Y, Shirai D, Miyazaki M, Imai N, Yokokawa T, et al. Plasma interleukin-6 levels in continuous ambulatory peritoneal dialysis and hemodialysis patients. Nephron. 1992;61(2):132-4. https://doi.org/10.1159/000186859 PMid:1630534 DOI: https://doi.org/10.1159/000186859
Cavaillon JM, Poignet JL, Fitting C, Delons S. Serum interleukin-6 in long-term hemodialyzed patients. Nephron. 1992;60(3):307-13. https://doi.org/10.1159/000186770 PMid:1565183 DOI: https://doi.org/10.1159/000186770
Visiedo L, Rey L, Rivas F, López F, Tortajada B, Giménez R, et al. The impact of nutritional status on health-related quality of life in hemodialysis patients. Sci Rep. 2022;12(1):3029. https://doi.org/10.1038/s41598-022-07055-0 PMid:35194119 DOI: https://doi.org/10.1038/s41598-022-07055-0
Sohrabi Z, Eftekhari MH, Eskandari MH, Rezaeianzadeh A, Sagheb MM. Malnutrition-inflammation score and quality of life in hemodialysis patients: Is there any correlation? Nephrourol Mon. 2015;7(3):e27445. https://doi.org/10.5812/numonthly.7(3)2015.27445 PMid:26034747 DOI: https://doi.org/10.5812/numonthly.7(3)2015.27445
Aldámiz-Echevarría L, Andrade F. Asymmetric dimethylarginine, endothelial dysfunction and renal disease. Int J Mol Sci. 2012;13(9):11288-311. https://doi.org/10.3390/ijms130911288 PMid:23109853 DOI: https://doi.org/10.3390/ijms130911288
Oliva-Damaso E, Oliva-Damaso N, Rodriguez-Esparragon F, Payan J, Baamonde-Laborda E, Gonzalez-Cabrera F, et al. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines in chronic kidney disease: A clinical approach. Int J Mol Sci. 2019;20:(15):3668. https://doi.org/10.3390/ijms20153668 PMid:31357472 DOI: https://doi.org/10.3390/ijms20153668
Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, et al. Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: Results from the multicenter coronary artery risk determination investigating the influence of ADMA concentration (CARDIAC) study. Am Heart J. 2006;152(3):493. https://doi.org/10.1016/j.ahj.2006.06.005 PMid:16923419 DOI: https://doi.org/10.1016/j.ahj.2006.06.005
Kocaman SA. Asymmetric dimethylarginine, NO and collateral growth. Anadolu Kardiyol Derg. 2009;9(5):417-20. PMid:19819795
Kielstein JT, Böger RH, Bode-Böger SM, Schäffer J, Barbey M, Koch KM, et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol. 1999;10(3):594-600. https://doi.org/10.1681/ASN.V103594 PMid:10073610 DOI: https://doi.org/10.1681/ASN.V103594
Wang Y, Gao L. Inflammation and cardiovascular disease associated with hemodialysis for end-stage renal disease. Front Pharmacol. 2022;13:800950. https://doi.org/10.3389/fphar.2022.800950 PMid:35222026 DOI: https://doi.org/10.3389/fphar.2022.800950
Widiasta A, Wahyudi K, Nugrahapraja H, Sribudiani Y, Rachmadi D. The unique difference between serum level of soluble urokinase plasminogen activator receptor (suPAR) in steroid-resistant nephrotic syndrome children treated with an alkylating agent and calcineurin inhibitors. J Compr Pediatr. 2021;12(2):e109912. https://doi.org/10.5812/compreped.109912 DOI: https://doi.org/10.5812/compreped.109912
Rachmadi D, Widiasta A, Pusparani C, Wahyudi K, Nugrahapraja H, Sribudiani Y. Higher baseline integrin beta-1 level associated with possible increase in the remission of steroid-resistant nephrotic syndrome using cyclophosphamide treatment. Int J Pharm Res. 2021;13(2):4223-32. https://doi.org/10.31838/ijpr/2021.13.02.517 DOI: https://doi.org/10.31838/ijpr/2021.13.02.517
Lh DD, Widiasta A, Ghrahani R, Hilmanto D, Rachmadi D. Therapeutic plasma exchange as a promising therapeutic modality in the management of acute cytokine storms and secondary prevention of chronic kidney disease in children during pandemic. Int J Pharm Res. 2021;13(2):4473-86. https://10.31838/ijpr/2021.13.02.259 DOI: https://doi.org/10.31838/ijpr/2021.13.02.259
Su H, Lei CT, Zhang C. Interleukin-6 signaling pathway and its role in kidney disease: An update. Front Immunol. 2017;8:405. https://doi.org/10.3389/fimmu.2017.00405 PMid:28484449 DOI: https://doi.org/10.3389/fimmu.2017.00405
Bolton CH, Downs LG, Victory JG, Dwight JF, Tomson CR, Mackness MI, et al. Endothelial dysfunction in chronic renal failure: Roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant. 2001;16(6):1189-97. https://doi.org/10.1093/ndt/16.6.1189 PMid:11390719 DOI: https://doi.org/10.1093/ndt/16.6.1189
Nawawi H, Osman NS, Annuar R, Khalid BA, Yusoff K. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin. Atherosclerosis. 2003;169(2):283-91. https://doi.org/10.1016/S0021-9150(03)00193-X PMid:12921980 DOI: https://doi.org/10.1016/S0021-9150(03)00193-X
Aguilera A, Sánchez-Tomero JA, Bajo MA, Ruiz-Caravaca ML, Alvarez V, del Peso G, et al. Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. Adv Perit Dial. 2003;19:240-5. PMid:14763071
Stenvinkel P, Chung SH, Heimbürger O, Lindholm B. Malnutrition, inflammation, and atherosclerosis in peritoneal dialysis patients. Perit Dial Int. 2001;21 Suppl 3:S157-62. https://doi.org/10.1177/089686080102103S27 PMid:11887812 DOI: https://doi.org/10.1177/089686080102103S27
Demir M, Kucuk A, Sezer MT, Altuntas A, Kaya S. Malnutrition-inflammation score and endothelial dysfunction in hemodialysis patients. J Ren Nutr. 2010;20(6):377-83. https://doi.org/10.1053/j.jrn.2010.03.002 PMid:20663689 DOI: https://doi.org/10.1053/j.jrn.2010.03.002
Melikian N, Wheatcroft SB, Ogah OS, Murphy C, Chowienczyk PJ, Wierzbicki AS, et al. Asymmetric dimethylarginine and reduced nitric oxide bioavailability in young black African men. Hypertension. 2007;49(4):873-7. https://doi.org/10.1161/01.HYP.0000258405.25330.80 PMid:17261643 DOI: https://doi.org/10.1161/01.HYP.0000258405.25330.80
Juonala M, Viikari JS, Alfthan G, Marniemi J, Kähönen M, Taittonen L, et al. Brachial artery flow-mediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study. Circulation. 2007;116(12):1367-73. https://doi.org/10.1161/CIRCULATIONAHA.107.690016 PMid:17724260 DOI: https://doi.org/10.1161/CIRCULATIONAHA.107.690016
Cupisti A, Saba A, D’Alessandro C, Meola M, Panicucci E, Panichi V, et al. Dimethylarginine levels and nutritional status in hemodialysis patients. J Nephrol. 2009;22(5):623-9. PMid:19809995
Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, et al. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: A systematic review. Intensive Care Med. 2012;38(9):1418-28. https://doi.org/10.1007/s00134-012-2613-1 PMid:22706919 DOI: https://doi.org/10.1007/s00134-012-2613-1
Valencia VC, Rodríguez OM, Sandoval ME, Bermúdez JA, Castellanos SG, de la Cruz CO, et al. Prevalence of malnutrition-inflammation complex syndrome and its correlation with thyroid hormones in chronic haemodialysis patients. Nefrologia (Engl Ed). 2018;38(1):57-63. https://doi.org/10.1016/j.nefroe.2017.11.019 PMid:29102271 DOI: https://doi.org/10.1016/j.nefroe.2017.11.019
Kaysen GA, Rathore V, Shearer GC, Depner TA. Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int. 1995;48(2):510-6. https://doi.org/10.1038/ki.1995.321 PMid:7564120 DOI: https://doi.org/10.1038/ki.1995.321
Schepers E, Barreto DV, Liabeuf S, Glorieux G, Eloot S, Barreto FC, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(10):2374-83. https://doi.org/10.2215/CJN.01720211 PMid:21817129 DOI: https://doi.org/10.2215/CJN.01720211
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2022 Stella Palar, Frans Erwin Wantania, Hanna Honoris (Author)
![Creative Commons License](http://i.creativecommons.org/l/by-nc/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0