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The role of cytokines in the formation and prediction of refractory neprotic syndrome in membranous nepropathy
https://doi.org/10.36485/1561-6274-2025-29-4-68-76
EDN: PKDDFK
Abstract
BACKGROUND. The lack of reliable methods for predicting the development of treatment-refractory membranous nephropathy (MNP) with nephrotic syndrome (NS) is due to a lack of understanding of the mechanisms of NS resistance to treatment.
THE AIM: to study the features of the cytokine status in patients with MNP and their significance in the formation and prediction of refractory NS.
PATIENTS AND METHODS. The study was prospective and included a cohort of patients with MPN who were admitted to the nephrology department with active NS and were subsequently followed up for 24 months in the nephrologist's office at the polyclinic. The study endpoint was the completion of the 24-month follow-up period, during which the study group was divided into two subgroups based on their response to treatment: a subgroup of patients with treatment-responsive NS and a subgroup of patients with treatment-refractory NS. At the beginning of treatment and after 24 months, blood and urine samples were collected to determine the levels of cytokines IL-2, IL-4, IL-8, IL-10, and IL-17A, which were stored at -70°C until analysis. The levels of cytokines were determined simultaneously using enzyme-linked immunosorbent assay at the end of treatment.
RESULTS. The study included 136 patients with MNP: 98 patients with the debut of NS, 25 with persistent NS, and 13 with frequent NS relapses. After 24 months of follow-up, 78 patients were found to have NS remission. 58 patients were refractory to treatment. In patients with refractory NS, blood and urine samples showed increased baseline levels of pro-inflammatory cytokines IL-8 and IL-17A and decreased levels of IL-10 compared to those in patients who achieved disease remission.
CONCLUSION. According to the results of the study, the initial normalized by creatinine levels of IL-8 and IL-17A in the urine can be used as biomarkers for early prediction of refractory NS in MPN
Supporting agencies: The study was carried out with the financial support of I.N. Ulyanov Chuvash State University, in particular, intra-university grants No. 11-20 and No. 15-23.
About the Authors
S. I. Kudryashov
I.N. Ulianov Chuvash State University
Russian Federation
Russian Federation
Associate Professor Sergey I. Kudryashov, MD PhD
428015, Cheboksary, Moskovsky ave., build 15
Phone: +7(917)6523499
L. M. Karzakova
I.N. Ulianov Chuvash State University
Russian Federation
Russian Federation
Prof. Luiza M. Karzakova, MD, PhD, DMedSci
428015, Cheboksary, Moskovsky ave., build 15
Phone: +7(903)3588289
M. A. Stenina
N.I. Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Prof. Marina A. Stenina, MD, PhD, DMedSci
117997, Moscow, Ostrovityanova str., build 1
Phone: +7(906)7463668
References
1. Lv JC, Zhang X. Prevalence and Disease Burden of Chronic Kidney Disease. Adv Exp Med Biol 2019;1165:3–15. doi: 10.1007/978-981-13-8871-2_1
2. Wang L, Xu X, Zhang M et al. Prevalence of Chronic Kidney Disease in China: Results From the Sixth China Chronic Disease and Risk Factor Surveillance. JAMA Intern Med 2023;183(4);298–310. doi:10.1001/jamainternmed.2022.6817
3. Abd ElHafeez S, Kramer A, Arici M et al. Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry. Nephrol Dial Transplant 2024;39(9):1449–1460. doi:10.1093/ndt/gfae034
4. Alsharhan L, Beck LH Jr. Membranous Nephropathy: Core Curriculum 2021. Am J Kidney Dis 2021;77(3):440–453. doi:10.1053/j.ajkd.2020.10.009
5. Ronco P, Beck L, Debiec H et al. Membranous nephropathy. Nat Rev Dis Primers 2021;7(1):69. doi: 10.1038/s41572-021-00303-z
6. Bobkova IN, Bulanov NM, Zakharova EV et al. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Nephrology and Dialysis 2022;24(4):577–874. (In Russ.) doi:10.28996/2618-9801-2022-4-577-874
7. Simbirtsev AS. Immunopharmacological aspects of the cytokine system. Byulleten sibirskoy meditsiny (Bulletin of Siberian Medicine) 2019;18(1):84–95. (In Russ.) doi: 10.20538/1682-0363-2019-1-84–95
8. Karzakova LM, Kudryashov SI, Shestipalova MV, Leontyeva EV. Determining of cytokine levels in the urine in clinical practice. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics) 2019;64(5):287–293. (In Russ.) doi: 10.18821/0869-2084-2019-64-5-287-293
9. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013;3(1):1–150
10. Bobkova IN, Kozlovskaya LV, Tsygin AN, Shilov EM. Clinical guidelines for the diagnosis and treatment of membranous nephropathy. Nephrology (Saint-Petersburg) 2014:18(4):93–100. (In Russ.)
11. Moledina DG, Wilson FP, Pober JS et al. Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight 2019;4(10):e127456. doi:10.1172/jci.insight.127456
12. Limonte CP, Prince DK, Hoofnagle AN et al. Kidney Tubular Biomarkers in Type 1 Diabetes – Longitudinal Analysis of 2 Cohorts. Kidney Int Rep 2025;10(7):2311–2322. doi:10.1016/j.ekir.2025.04.057
13. Matsushima K, Yang D, Oppenheim JJ. Interleukin-8: An evolving chemokine. Cytokine 2022;153:155828. doi:10.1016/j.cyto.2022.155828
14. Cho MH, Lee HS, Choe BH et al. Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability. Am J Nephrol 2003;23:260–266. doi: 10.1159/000072065
15. Huber TB, Reinhardt HC, Exner M et al. Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol 2002;168(12):6244–6252. doi:10.4049/jimmunol.168.12.6244
16. Chung SH, Ye XQ, Iwakura Y. Interleukin-17 family members in health and disease. Int Immunol 2021;33(12):723–729. doi:10.1093/intimm/dxab075
17. Yan XH, Dong QL, Jin G et al. Effect of Interleukin-17 gene on glomerular ultrastructure and podocyte injury in adriamycin nephropathy rat models. J Biol Regul Homeost Agents 2021;35:1001–1010. doi: 10.23812/20-741-A
18. Efe O, So PNH, Anandh U et al. An Updated Review of Membranous Nephropathy. Indian J Nephrol 2024;34(2):105–118. doi: 10.25259/ijn_317_23
Review
For citations:
Kudryashov S.I., Karzakova L.M., Stenina M.A. The role of cytokines in the formation and prediction of refractory neprotic syndrome in membranous nepropathy. Nephrology (Saint-Petersburg). 2025;29(4):68-76. (In Russ.) https://doi.org/10.36485/1561-6274-2025-29-4-68-76. EDN: PKDDFK
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