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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Relation between Soluble CD14 Levels, Inflammation, Subclinical Atherosclerosis and Mortality in Hemodialysis Patients

Author(s): Amany Mohamed Abdallah, Heba Elhakeem, Mohamed Basiouny Yahia*, Eman Mohy Ibrahim Youssef, Nashwa El-Khouly, Ghada Fathy Elmohaseb, Eman Abu-Elnasr Awad, Marwa Mohamed Hassan, Esam Mohamed Ghamry, Mohamed Rashed Abdelhamed, Essam Kotb and Tamer Mohamed Mahmoud

Volume 23, Issue 6, 2023

Published on: 30 December, 2022

Page: [843 - 849] Pages: 7

DOI: 10.2174/1871530322666221011091606

Price: $65

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Abstract

Background and Aim: Chronic kidney disease (CKD) is characterized by persistent lowgrade inflammation. Soluble CD14 (sCD14) is involved in many pathological conditions, including inflammation and atherosclerosis. The present study aimed to assess the relationship between sCD14 levels, subclinical atherosclerosis (SCA), inflammation and mortality in Egyptian hemodialysis (HD) patients.

Patients and Methods: The present longitudinal study included 62 HD patients. All patients were submitted to careful history taking, thorough clinical examination and laboratory assessment for high-sensitivity C-reactive protein (hsCRP) and sCD14. Carotid intima-media thickness (CIMT) was also assessed. Patients were followed for a maximum of 18 months. The primary outcome is patients’ mortality. Data were statistically analyzed using standard descriptive, comparative, correlative and regression methods.

Results: The present study was conducted on 62 HD patients. They comprised 34 males and 28 females with an age of 54.6 ± 9.0 years. At the end of follow-up, 12 patients (19.4 %) died. It was shown that survivors had significantly lower hsCRP levels (104.2 ± 38.2 versus 134.1 ± 15.3 mg/dL, p < 0.001), lower sCD14 levels (32.7 ± 10.3 versus 47.4 ± 18.4 μg/mL, p = 0.02) and lower CIMT (1.32 ± 0.5 versus 1.5 ± 0.2 mm, p = 0.049). sCD14 levels were significantly correlated with hsCRP (r = 0.4, p = 0.001) and CIMT (r = 0.31, p = 0.013). Multivariate analysis identified HD duration [HR (95% CI): 1.02 (1.0-1.04), p = 0.021] and sCD14 levels [HR (95% CI): 1.06 (1.0-1.12), p = 0.026] as significant predictors of patients’ survival.

Conclusions: sCD14 levels in this cohort of HD patients are well-correlated with hsCRP levels and CIMT. In addition, they are significant predictors of patients’ mortality.

Keywords: Chronic kidney disease, hemodialysis, soluble CD14, atherosclerosis, inflammation, hsCRP.

Graphical Abstract
[1]
Ruiz, O.M.; Rayego, M.S.; Lamas, S.; Ortiz, A.; Rodrigues, D.R.R. Targeting the progression of chronic kidney disease. Nat. Rev. Nephrol., 2020, 16(5), 269-288.
[http://dx.doi.org/10.1038/s41581-019-0248-y] [PMID: 32060481]
[2]
Ebert, T.; Pawelzik, S.C.; Witasp, A.; Arefin, S.; Hobson, S.; Kublickiene, K.; Shiels, P.G.; Bäck, M.; Stenvinkel, P. Inflammation and prem-ature ageing in chronic kidney disease. Toxins, 2020, 12(4), 227.
[http://dx.doi.org/10.3390/toxins12040227] [PMID: 32260373]
[3]
Mazzaferro, S.; Bagordo, D.; De Martini, N.; Pasquali, M.; Rotondi, S.; Tartaglione, L.; Stenvinkel, P. Inflammation, oxidative stress, and bone in chronic kidney disease in the osteoimmunology era. Calcif. Tissue Int., 2021, 108(4), 452-460.
[http://dx.doi.org/10.1007/s00223-020-00794-0] [PMID: 33388898]
[4]
Dai, L.; Schurgers, L.J.; Shiels, P.G.; Stenvinkel, P. Early vascular ageing in chronic kidney disease: Impact of inflammation, vitamin K, senescence and genomic damage. Nephrol. Dial. Transplant., 2020, 35(Suppl. 2), 31-37.
[http://dx.doi.org/10.1093/ndt/gfaa006] [PMID: 32162665]
[5]
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.
[http://dx.doi.org/10.3390/jcm9082359] [PMID: 32718053]
[6]
Provenzano, M.; Andreucci, M.; De Nicola, L.; Garofalo, C.; Battaglia, Y.; Borrelli, S.; Gagliardi, I.; Faga, T.; Michael, A.; Mastroroberto, P.; Serraino, G.F.; Licastro, N.; Ielapi, N.; Serra, R. The role of prognostic and predictive biomarkers for assessing cardiovascular risk in chronic kidney disease patients. BioMed Res. Int., 2020, 2020, 2314128.
[http://dx.doi.org/10.1155/2020/2314128] [PMID: 33102575]
[7]
Ciesielska, A.; Matyjek, M.; Kwiatkowska, K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci., 2021, 78(4), 1233-1261.
[http://dx.doi.org/10.1007/s00018-020-03656-y] [PMID: 33057840]
[8]
Wu, Z.; Zhang, Z.; Lei, Z.; Lei, P. CD14: Biology and role in the pathogenesis of disease. Cytokine Growth Factor Rev., 2019, 48, 24-31.
[http://dx.doi.org/10.1016/j.cytogfr.2019.06.003] [PMID: 31296363]
[9]
Merino, A.; Portolés, J.; Selgas, R.; Ojeda, R.; Buendia, P.; Ocaña, J.; Bajo, M.A.; Del Peso, G.; Carracedo, J.; Ramírez, R.; Martín, M.A.; Aljama, P. Effect of different dialysis modalities on microinflammatory status and endothelial damage. Clin. J. Am. Soc. Nephrol., 2010, 5(2), 227-234.
[http://dx.doi.org/10.2215/CJN.03260509] [PMID: 20056757]
[10]
Merino, A.; Nogueras, S.; Buendía, P.; Ojeda, R.; Carracedo, J.; Ramirez, C.R.; Martin, M.A.; Aljama, P. Microinflammation and endothelial damage in hemodialysis. Contrib. Nephrol., 2008, 161, 83-88.
[http://dx.doi.org/10.1159/000130412] [PMID: 18451662]
[11]
Ulrich, C.; Heine, G.H.; Seibert, E.; Fliser, D.; Girndt, M. Circulating monocyte subpopulations with high expression of angiotensin-converting enzyme predict mortality in patients with end-stage renal disease. Nephrol. Dial. Transplant., 2010, 25(7), 2265-2272.
[http://dx.doi.org/10.1093/ndt/gfq012] [PMID: 20150168]
[12]
Rogacev, K.S.; Seiler, S.; Zawada, A.M.; Reichart, B.; Herath, E.; Roth, D.; Ulrich, C.; Fliser, D.; Heine, G.H. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur. Heart J., 2011, 32(1), 84-92.
[http://dx.doi.org/10.1093/eurheartj/ehq371] [PMID: 20943670]
[13]
Hassan, M.O.; Dix, P.T.; Duarte, R.; Dickens, C.; Naidoo, S.; Vachiat, A.; Grinter, S.; Manga, P.; Naicker, S. Association of chronic inflam-mation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease. PLoS One, 2020, 15(7), e0232741.
[http://dx.doi.org/10.1371/journal.pone.0232741] [PMID: 32649699]
[14]
Edalat, N.M.; Qlich, K.M.; Salehi, F.; Zameni, F. Geriatric nutritional risk index: A mortality predictor in hemodialysis patients. Saudi J. Kidney Dis. Transpl., 2015, 26(2), 302-308.
[http://dx.doi.org/10.4103/1319-2442.152445] [PMID: 25758879]
[15]
Stein, J.H.; Korcarz, C.E.; Hurst, R.T.; Lonn, E.; Kendall, C.B.; Mohler, E.R.; Najjar, S.S.; Rembold, C.M.; Post, W.S. Use of carotid ultra-sound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force. J. Am. Soc. Echocardiogr., 2008, 21(2), 93-111.
[http://dx.doi.org/10.1016/j.echo.2007.11.011] [PMID: 18261694]
[16]
Mulumba, C.; Lebughe, P.; Mbuyi, M.J.M.; Makulo, J.R.; Lepira, F.; Mukaya, J.; Westhovens, R.; Verschueren, P.; Malemba, J.J. Prevalence and associated factors of subclinical atherosclerosis in rheumatoid arthritis at the university hospital of Kinshasa. BMC Rheumatol., 2019, 3(1), 37.
[http://dx.doi.org/10.1186/s41927-019-0085-4] [PMID: 31517250]
[17]
Raj, D.S.C.; Shah, V.O.; Rambod, M.; Kovesdy, C.P.; Kalantar, Z.K. Association of soluble endotoxin receptor CD14 and mortality among patients undergoing hemodialysis. Am. J. Kidney Dis., 2009, 54(6), 1062-1071.
[http://dx.doi.org/10.1053/j.ajkd.2009.06.028] [PMID: 19699018]
[18]
Feroze, U.; Kalantar, Z.K.; Sterling, K.A.; Molnar, M.Z.; Noori, N.; Benner, D.; Shah, V.; Dwivedi, R.; Becker, K.; Kovesdy, C.P.; Raj, D.S. Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients. J. Ren. Nutr., 2012, 22(3), 317-326.
[http://dx.doi.org/10.1053/j.jrn.2011.05.004] [PMID: 21880509]
[19]
Raj, D.S.C.; Carrero, J.J.; Shah, V.O.; Qureshi, A.R.; Bárány, P.; Heimbürger, O.; Lindholm, B.; Ferguson, J.; Moseley, P.L.; Stenvinkel, P. Soluble CD14 levels, interleukin 6, and mortality among prevalent hemodialysis patients. Am. J. Kidney Dis., 2009, 54(6), 1072-1080.
[http://dx.doi.org/10.1053/j.ajkd.2009.06.022] [PMID: 19733948]
[20]
Navarro, G.J.F.; Mora, F.C.; De Fuentes, M.M.; Donate, C.J.; Cazaña, P.V.; García, P.J. Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients. Clin. J. Am. Soc. Nephrol., 2011, 6(9), 2272-2279.
[http://dx.doi.org/10.2215/CJN.01650211] [PMID: 21784820]
[21]
Poesen, R.; Ramezani, A.; Claes, K.; Augustijns, P.; Kuypers, D.; Barrows, I.R.; Muralidharan, J.; Evenepoel, P.; Meijers, B.; Raj, D.S. As-sociations of soluble CD14 and endotoxin with mortality, cardiovascular disease, and progression of kidney disease among patients with CKD. Clin. J. Am. Soc. Nephrol., 2015, 10(9), 1525-1533.
[http://dx.doi.org/10.2215/CJN.03100315] [PMID: 26153127]
[22]
Losito, A.; Kalidas, K.; Santoni, S.; Errico, R.; Jeffery, S. Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients. Blood Purif., 2005, 23(2), 128-133.
[http://dx.doi.org/10.1159/000083207] [PMID: 15640605]
[23]
Nockher, W.A.; Scherberich, J.E. Monocyte cell-surface CD14 expression and soluble CD14 antigen in hemodialysis: Evidence for chronic exposure to LPS. Kidney Int., 1995, 48(5), 1469-1476.
[http://dx.doi.org/10.1038/ki.1995.436] [PMID: 8544403]
[24]
Kawanaka, N.; Nagake, Y.; Yamamura, M.; Makino, H. Expression of Fc gamma receptor III (CD16) on monocytes during hemodialysis in patients with chronic renal failure. Nephron J., 2002, 90(1), 64-71.
[http://dx.doi.org/10.1159/000046316] [PMID: 11744807]
[25]
Oka, Y.; Miyazaki, M.; Takatsu, S.; Kunitomo, K.; Kokumai, Y.; Matsuda, H.; Maruyama, M. Lowering of oxidative stress in hemodialysis patients by dialysate cleaning: In relation to arteriosclerosis. Ther. Apher. Dial., 2004, 8(4), 313-319.
[http://dx.doi.org/10.1111/j.1526-0968.2004.00141.x] [PMID: 15274683]
[26]
Martin, T.R.; Wurfel, M.M.; Zanoni, I.; Ulevitch, R. Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness. EBioMedicine, 2020, 57, 102836.
[http://dx.doi.org/10.1016/j.ebiom.2020.102836] [PMID: 32574958]

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