Immunomodulatory Pathways of Some Biomarkers in Individuals with Renal Failure

Authors

DOI:

https://doi.org/10.14500/aro.12474

Keywords:

Antinuclear antibody, Chronic kidney disease, Immunoglobulin, Inflammatory and anti inflammatory cytokines

Abstract

This study investigates the correlation between renal failure and immunoinflammatory marker pathways. Specimens were obtained from the Hemodialysis Center located in the cities of Ranya and QaladezeSulaymaniyah, KRG, Iraq. The investigation included a well-defined cohort of 120 individuals (60 patients and 60 control participants), comprising both sexes, during the period from October to December 2024. Participants ranged in age from 40 to 60 years. The concentrations of immunoglobulins (IgA, IgM, and IgG) were measured using the Cobas 6000 analyzer, while IgE levels were assessed with the Cobas e 411 analyzer. The enzyme-linked immunosorbent assay was utilized for detecting the variations of cytokines (Tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10) and antinuclear antibody (ANA). Erythrocyte sedimentation rate (ESR) was determined using the automated ESR analyzer. Individuals diagnosed with end-stage renal disease (ESRD) exhibited significant immunological alterations, marked by a significant decrease in IgA, IgM, and IgG levels and accompanied by a substantial elevation in IgE levels. The current investigation revealed a markedly elevated ESR, tumor necrosis factor- alpha (TNF-α), IL-6, and IL-10 in reference to the healthy subjects. ANA titers exhibited a slight increase within the patient population. This immunological dysregulation is further associated with elevated levels of TNF-α, IL-6, and IL-10, indicating a persistent systemic inflammatory state. The synchronous augmentation of ESR and TNF-α and IL-6 confirms their potential utility as prognostic biomarkers for chronic inflammation in ESRD patients. Observation of elevated inflammatory markers in females indicates a potential gender-specific variation in immune response pathways within this clinical population.

Downloads

Download data is not yet available.

Author Biography

Ahmed F. Shallal, Department of Biology, College of Science, University of Raparin, Rania 46012 Kurdistan Region – F.R. Iraq

Ahmed F. Shallal is an Assistant Prof. at the Department of Biology , College of Science , Raparin University. I got the B.Sc. degree in Biology , the M.Sc. degree in physiology and the Ph.D. degree in Immunology . My research interests are in immunology, immunophysiology and clinical immunology.

References

Anis, S., Parveen, J., Musharraf, W., Ahmed, E., and Muzaffar, R., 2016. Can we use serum and urine immunoglobulin levels as biomarkers in patients with glomerulonephritis? Immunopathologia Persa, 3(2), p.e10. DOI: https://doi.org/10.15171/ipp.2017.02

Boes, M., 2000. Role of natural and immune IgM antibodies in immune responses. Molecular Immunology, 21(7), pp.361-367.

Brierly, G., Celentano, A., Breik, O., Moslemivayeghan, E., Patini, R., McCullough, M., and Yap, T., 2023. Tumour necrosis factor alpha (TNF-α) and oral squamous cell carcinoma. Cancers (Basel), 15(6), p.1841. DOI: https://doi.org/10.3390/cancers15061841

Brigden, M.L., 1999. Clinical utility of the erythrocyte sedimentation rate. American Family Physician, 60(5), pp.1443-1450.

Buckenmayer, A., Dahmen, L., Hoyer, J., Kamalanabhaiah, S., and Haa, C.S., 2022. Erythrocyte sedimentation rate in patients with renal insufficiency and renal replacement therapy. Laboratory Medicine, 53(5), pp.483-487. DOI: https://doi.org/10.1093/labmed/lmac018

Carlini, V., Noonan, D.M., Abdalalem, E., Goletti, D., Sansone, C., Calabrone, L., and Albini, A., 2023. The multifaceted nature of IL-10: Regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and postCOVID conditions. Frontiers in Immunology, 14, p.1161067. DOI: https://doi.org/10.3389/fimmu.2023.1161067

Carrero, J.J., and Stenvinkel, P., 2018. Inflammation in end-stage renal disease--what have we learned in 10 years? Seminars in Dialysis, 31(6), pp.498-509. Cohen, G., 2020. Immune dysfunction in uremia 2020. Toxins (Basel), 12(7), p.439.

Galli, S.J., and Tsai, M., 2012. IgE and mast cells in allergic disease. Nature Medicine, 18(5), pp.693-704. DOI: https://doi.org/10.1038/nm.2755

Ge, Q., Gu, X., Yu, W., Zhang, G., Liang, W., Li, M., Zhai, G., and Yan, M., 2022. Antinuclear antibodies in healthy population: Positive association with abnormal tissue metabolism, inflammation and immune dysfunction. International Immunopharmacology, 113, p.109292. DOI: https://doi.org/10.1016/j.intimp.2022.109292

González-Lafuente, L., Mercado-García, E., Vázquez-Sánchez, S., GonzálezMoreno, D., Boscá, L., Fernández-Velasco, M., Segura, J., Makoto Kuro, O.M., Ruilope, L.M., Liaño, F., and Ruiz-Hurtado, G., 2024. Interleukin-6 as a prognostic marker in acute kidney injury and its klotho-dependent regulation. Nefrología (English Edition), 44(6), pp.818-829. DOI: https://doi.org/10.1016/j.nefroe.2024.11.010

Hao, X.M., Liu, Y., Hailaiti, D., Gong, Y., Zhang, X.D., Yue, B.N., Liu, J.P., Wu, X.L., Yang, K.Z., Wang, J., and Liu, Q.G., 2024. Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy. Frontiers in Immunology, 15, p.1333170. DOI: https://doi.org/10.3389/fimmu.2024.1333170

Imig, J.D., and Ryan, M.J., 2013. Immune and inflammatory role in renal disease. Comprehensive Physiology, 3(2), pp.957-1003. DOI: https://doi.org/10.1002/j.2040-4603.2013.tb00511.x

Jang, D.I., Lee, A.H., Shin, H.Y., Song, H.R., Park, J.H., Kang, T.B., Lee, S.R., and Yang, S.H., 2021. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. International Journal of Molecular Sciences, 22(5), p.2719. DOI: https://doi.org/10.3390/ijms22052719

Kalantar-Zadeh, K., Jafar, T.H., Nitsch, D., Neuen, B.L., and Perkovic, V., 2021. Chronic kidney disease. The Lancet, 398(10302), pp.786-802. DOI: https://doi.org/10.1016/S0140-6736(21)00519-5

Kalantar-Zadeh, K., Kopple, J.D., Block, G., and Humphreys, M.H., 2021. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. American Journal of Kidney Diseases, 38(6), pp.1251-1263. DOI: https://doi.org/10.1053/ajkd.2001.29222

Kato, S., Chmielewski, M., Honda, H., Pecoits-Filho, R., Matsuo, S., Yuzawa, Y., Tranaeus, A., Stenvinkel, P., and Lindholm, B., 2019. Aspects of immune dysfunction in end-stage renal disease. Clinical Journal of the American Society of Nephrology, 14(2), pp.183-190.

lein, S.L., and Flanagan, K.L., 2016. Sex differences in immune responses. Nature Reviews Immunology, 16(10), pp.626-638. DOI: https://doi.org/10.1038/nri.2016.90

Kurts, C., Panzer, U., Anders, H.J., and Rees, A.J., 2013. The immune system and kidney disease: Basic concepts and clinical implications. Nature Reviews Immunology, 13(10), pp.738-753. DOI: https://doi.org/10.1038/nri3523

Lee, J.H., Lee, S.Y., Kim, J.S., Kim Da, R., Jung, S.W., Jeong, K.H., Lee, T.W., Lee, Y.H., Kim, Y.G., Moon, J.Y., Lee, S.H., and Ihm, C.G., 2016. Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy. Kidney Research and Clinical Practice, 35(3), pp.147-151. DOI: https://doi.org/10.1016/j.krcp.2016.07.002

Moore, K.W., De Waal Malefyt, R., Coffman, R.L., and O’Garra, A., 2001. Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology, 19, pp.683-765. DOI: https://doi.org/10.1146/annurev.immunol.19.1.683

Nakayama, K., Ohsawa, I., Maeda-Ohtani, A., Murakoshi, M., Horikoshi, S., and Tomino, Y., 2008. Prediction of diagnosis of immunoglobulin A nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic grading. Journal of Clinical Laboratory Analysis, 22(2), pp.114-118. DOI: https://doi.org/10.1002/jcla.20227

Nazar, C.M., Bashir, F., Izhar, S., and Anderson, J., 2015. Overview of management of acute renal failure and its evaluation; A case analysis. Journal of Nephropharmacology, 4(1), pp.17-22.

Petreski, T., Piko, N., Ekart, R., Hojs, R., and Bevc, S., 2021. Review on inflammation markers in chronic kidney disease. Biomedicines, 9(2), p.182. DOI: https://doi.org/10.3390/biomedicines9020182

Pisetsky, D.S., 2021. Antinuclear antibody testing-misunderstood or misused? Nature Reviews Rheumatology, 17(12), pp.715-723.

Pisetsky, D.S., Spencer, D.M., Lipsky, P.E., and Rovin, B.H., 2011. Assay variation in the detection of antinuclear antibodies in the sera of patients with established SLE. Arthritis Research and Therapy, 13(6), pp.911-913. DOI: https://doi.org/10.1136/annrheumdis-2017-212599

Samimi, Z., Kardideh, B., Chalabi, M., Zafari, P., and Taghadosi, M., 2020. The plasma tumor necrosis factor-α (TNF-α) does not have any correlation with disease activity in rheumatoid arthritis patients treated with disease modifying anti-rheumatic drugs (DMARDs). Brazilian Journal of Pharmaceutical Sciences, 56, p.e18551. DOI: https://doi.org/10.1590/s2175-97902019000418551

Singh, M.R., Yadav, K., Chaurasiya, N.D., and Singh, D., 2022. Immune system and mechanism of immunomodulation. In: Plants and Phytomolecules for Immunomodulation: Recent Trends and Advances. Springer Nature Singapore, Singapore, pp.1-31. DOI: https://doi.org/10.1007/978-981-16-8117-2_1

Stenvinkel, P., Pecoits-Filho, R., and Lindholm, B., 2020. Inflammation in endstage renal disease: The hidden enemy. Nephrology Dialysis Transplantation, 35(Suppl 2), pp.ii20-ii25.

Su, H., Lei, C.T., and Zhang, C., 2017. Interleukin-6 signaling pathway and its role in kidney disease: An update. Frontiers in Immunology, 8, p.405. DOI: https://doi.org/10.3389/fimmu.2017.00405

Sur, L.M., Floca, E., Sur, D.G., Colceriu, M.C., Samasca, G., and Sur, G., 2018. Antinuclear antibodies: Marker of diagnosis and evolution in autoimmune diseases. Laboratory Medicine, 49(3), pp.e62-e73. DOI: https://doi.org/10.1093/labmed/lmy024

Suzuki, H., Kiryluk, K., Novak, J., Moldoveanu, Z., Herr, A.B., Renfrow, M.B., and Wyatt, R.J., 2011. The pathophysiology of IgA nephropathy. Nature Reviews Nephrology, 7(12), pp.713-723.

Tan, Y., Yang, D., Fan, J., and Chen, Y., 2011. Elevated levels of immunoglobulin E may indicate steroid resistance or relapse in adult primary nephrotic syndrome, especially in minimal change nephrotic syndrome. Journal of International Medical Research, 39(6), pp.2307-2313. DOI: https://doi.org/10.1177/147323001103900629

Van Der Meide, P.H., and Schellekens, H., 1996. Cytokines and the immune response. Biotherapy, 8(3-4), pp.243-249. DOI: https://doi.org/10.1007/BF01877210

Wang, X.H., and Mitch, W.E., 2020. Mechanisms of muscle wasting in chronic kidney disease. Nature Reviews Nephrology, 10(9), pp.504-516. Webster, A.C., Nagler, E.V., Morton, R.L., and Masson, P., 2017. Chronic kidney disease. The Lancet, 389(10075), pp.1238-1252. DOI: https://doi.org/10.1016/S0140-6736(16)32064-5

Yarlagadda, D.L., Japa, P., Noorjahan, M., Sai Baba, K.S., Sreedevi, N.N., and Raju, B., 2019. Inflammatory and humoral immune status in chronic kidney disease. Indian Journal of Medical Biochemistry, 23(2), pp.30-308. DOI: https://doi.org/10.5005/jp-journals-10054-0108

Zhang, L., Wang, F., Wang, L., Wang, W., Liu, B., Liu, J., Chen, M., He, Q., Liao, Y., Yu, X., Chen, N., Zhang, J.E., Hu, Z., Liu, F., Hong, D., Ma, L., Liu, H., Zhou, X., Chen, J., Pan, L., Chen, W., Wang, W., Li, X., and Wang, H., 2012. Prevalence of chronic kidney disease in China: A cross-sectional survey. The Lancet, 379(9818), pp.815-822. DOI: https://doi.org/10.1016/S0140-6736(12)60033-6

Published

2025-12-06

How to Cite

Shallal, A. F. (2025) “Immunomodulatory Pathways of Some Biomarkers in Individuals with Renal Failure”, ARO-THE SCIENTIFIC JOURNAL OF KOYA UNIVERSITY, 13(2), pp. 326–333. doi: 10.14500/aro.12474.
Received 2025-07-27
Accepted 2025-10-16
Published 2025-12-06

Similar Articles

1 2 3 > >> 

You may also start an advanced similarity search for this article.