nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2024-28-4-100-110RMIGQEnefr-2356Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSВзаимосвязь повышенного уровня растворимого рецептора интерлейкина-2 в сыворотке крови и почечных исходов при гемофагоцитарном лимфогистиоцитозеThe relationship between elevated serum levels of soluble interleukin-2 receptor and renal outcomes in hemophagocytic lymphohistiocytosishttps://orcid.org/0000-0002-5686-273XАмириФ. С.AmiriF. S.

Фатима С. Амири, больничный комплекс Имама Хомейни, медицинский факультет Тегеранского университета медицинских наук 

1419733141, Иран, г. Тегеран, ул. М. Гариб

Assistant Prof. Fateme S. Amiri,  Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences

1419733141, Iran, Tehran, M. Gharib. St,

fa.shamekhi@gmail.comТегеранский университет медицинских наукИранTehran University of Medical SciencesIslamic Republic of Iran202419012025284100110Copyright © Амири Ф.С., 20252025Амири Ф.С.Amiri F.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2356ВВЕДЕНИЕ

ВВЕДЕНИЕ. Гемофагоцитарный лимфогистиоцитоз – группа врожденных и приобретенных заболеваний, возникающих вследствие нарушений регуляции иммунного ответа и характеризующихся гиперпродукцией гистиоцитов, а также цитотоксических T-лимфоцитов.

ЦЕЛЬ

ЦЕЛЬ: оценить взаимосвязь повышенного уровня растворимого интерлейкина-2 альфа в сыворотке крови и исходы поражения почек при гемофагоцитарном лимфогистиоцитозе.

ПАЦИЕНТЫ И МЕТОДЫ

ПАЦИЕНТЫ И МЕТОДЫ: В данном типе аналитических (экспериментальных) клинических исследований с дизайном рандомизированных клинических исследований, описанных в метаанализе, были проанализированы результаты обследования 283 пациентов с диагнозом гемофагоцитарный лимфогистиоцитоз и поражением почек. РЕЗУЛЬТАТЫ: при гемофагоцитарном лимфогистиоцитозе относительный риск и отношение шансов повышенного сывороточного уровня растворимого рецептора интерлейкина-2 в сыворотке крови развития почечной недостаточности и начала заместительной почечной терапии составили 1,04 и 1,12 в течение 28 дней соответственно, а межквартильный размах – 35,5 дня. Прогнозируемая вероятность смерти и необходимости начала заместительной почечной терапии при высоком сывороточном уровне растворимого рецептора интерлейкина-2 альфа не были статистически значимыми (р-значение 0,91 и р = 0,56 соответственно). Выявлена сильная отрицательная корреляция между сывороточным уровнем растворимого рецептора интерлейкина-2 альфа и кумулятивной частотой гипонатриемии, протеинурии, острого повреждения почек, азотемии. Статистически значимой взаимосвязи между данными анамнеза и сывороточным уровнем растворимого рецептора интерлейкина-2 альфа не выявлено.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ: высокий сывороточный уровень растворимого рецептора интерлейкина-2 в сыворотке альфа взаимосвязан в кумулятивной частотой негативных почечных исходов.

Дополнительные файлы (Таблицы) расположены по адресу: https://figshare.com/authors/Fateme_Shamekhi_Amiri/9040742

BACKGROUND

BACKGROUND: Hemophagocytic lymphohistiocytosis is an uncommon disease with a high mortality rate due to ineffective overactivation of the immune system. THE AIM: to assess the effect and prediction of elevated serum soluble interleukin-2 alpha level on kidney outcomes in hemophagocytic lymphohistiocytosis.

PATIENTS AND METHODS

PATIENTS AND METHODS: In this analytic (experimental) clinical studies type with randomized clinical trials design in meta-analysis article, two-hundred eighty-three patients with hemophagocytosis lymphohistiocytosis diagnosis and kidney impairment were investigated.

RESULTS

RESULTS: Relative risk and Odds ratio of elevated serum soluble interleukin-2 receptor alpha level on kidney failure progression to kidney replacement therapy was assessed 1.04 and 1.12 during 28 days and interquartile range of 35.5 days in hemophagocytic lymphohistiocytosis in this research. In prediction probability of death and chronic kidney disease progression to end-stage kidney disease led to kidney replacement therapy as outcome using high serum soluble interleukin-2 receptor alpha level was not significant statistically (p-value of 0.91 and p=0.56, respectively). There was strong negative correlation between soluble interleukin-2 receptor alpha levels and cumulative incidence of renal outcomes such as hyponatremia, proteinuria, acute kidney disease, elevated serum blood urea nitrogen and serum creatinine levels with rs of -0.7 and p-value of o.18. There was relationship between serum soluble interleukin-2 receptor alpha level and past medical history (p-value: 0.01) but overall this analysis did not show significant level statistically (p-value: 0.1).

CONCLUSION

CONCLUSION: There was a strong negative correlation between serum soluble interleukin-2 receptor alpha levels and cumulative incidence of renal outcomes. There wasn't a relationship between serum soluble interleukin-2 receptor alpha level and renal outcome after adjustment of confounding factors for renal function except for past medical history.

Sujpplement files (Tables) are located at: https://figshare.com/authors/Fateme_Shamekhi_Amiri/9040742  

 

 

острое повреждение почекгемофагоцитарный лимфогистиоцитозпрогнозируемая вероятностьсывороточный растворимый рецептор интерлейкина-2 альфаAcute kidney injuryHemophagocytic lymphohistiocytosisPredicted probabilityserum soluble interleukin-2 receptor alphaReferencesCiccarese C, Massari F, Tortora G. Acquired hemophagocytic syndrome: comment to the case report. Future Sci OA 2015 Nov 1;1(4):FSO31. doi: 10.4155/fso.15.29Ciccarese C, Massari F, Tortora G. Acquired hemophagocytic syndrome: comment to the case report. Future Sci OA 2015 Nov 1;1(4):FSO31. doi: 10.4155/fso.15.29Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood 2011 Oct 13;118(15):4041–4052. doi: 10.1182/blood-2011-03-278127Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood 2011 Oct 13;118(15):4041–4052. doi: 10.1182/blood-2011-03-278127Kaçar AG, Celkan TT. Hemophagocytic Lymphohistiocytosis. Balkan Med J 2022 Sep 9;39(5):309–317. doi: 10.4274/balkanmedj.galenos.2022.2022-4-83Kaçar AG, Celkan TT. Hemophagocytic Lymphohistiocytosis. Balkan Med J 2022 Sep 9;39(5):309–317. doi: 10.4274/balkanmedj.galenos.2022.2022-4-83Khare N, Jinkala SR, Kanungo S. Performance of HScore in Reactive Hemophagocytic Lymphohistiocytosis. Indian J Hematol Blood Transfus 2021 Apr;37(2):256–263. doi: 10.1007/s12288020-01342-4Khare N, Jinkala SR, Kanungo S. Performance of HScore in Reactive Hemophagocytic Lymphohistiocytosis. Indian J Hematol Blood Transfus 2021 Apr;37(2):256–263. doi: 10.1007/s12288020-01342-4Rodrigues CE, Endre ZH. Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine. Nephrology (Carlton) 2023 Feb;28(2):83–96. doi: 10.1111/nep.14132Rodrigues CE, Endre ZH. Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine. Nephrology (Carlton) 2023 Feb;28(2):83–96. doi: 10.1111/nep.14132Marks A, Fluck N, Prescott GJ, Robertson LM, Simpson WG, Smith WC, Black C. Definitions of progression in chronic kidney disease-predictors and relationship to renal replacement therapy in a population cohort with a 6 year follow-up. Nephrol Dial Transplant 2014 Feb;29(2):333–341. doi: 10.1093/ndt/gft393Marks A, Fluck N, Prescott GJ, Robertson LM, Simpson WG, Smith WC, Black C. Definitions of progression in chronic kidney disease-predictors and relationship to renal replacement therapy in a population cohort with a 6 year follow-up. Nephrol Dial Transplant 2014 Feb;29(2):333–341. doi: 10.1093/ndt/gft393Dik WA, Heron M. Clinical significance of soluble interleukin-2 receptor measurement in immune-mediated diseases. Neth J Med 2020 Sep;78(5):220–231. PMID: 33093245Dik WA, Heron M. Clinical significance of soluble interleukin-2 receptor measurement in immune-mediated diseases. Neth J Med 2020 Sep;78(5):220–231. PMID: 33093245Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol 2020 Sep;218:108515. doi: 10.1016/j.clim.2020.108515Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol 2020 Sep;218:108515. doi: 10.1016/j.clim.2020.108515La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JAM, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 2019 Jun 6;133(23):2465–2477. doi: 10.1182/ blood.2018894618La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JAM, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 2019 Jun 6;133(23):2465–2477. doi: 10.1182/ blood.2018894618Santos IO, Neto RP, Bom APKP. Hemophagocytic lymphohistiocytosis: a case series analysis in a pediatric hospital. Hematol Transfus Cell Ther 2023 Jan-Mar;45(1):32–37. doi: 10.1016/j. htct.2021.04.006Santos IO, Neto RP, Bom APKP. Hemophagocytic lymphohistiocytosis: a case series analysis in a pediatric hospital. Hematol Transfus Cell Ther 2023 Jan-Mar;45(1):32–37. doi: 10.1016/j. htct.2021.04.006Rajagopala S, Singh N. Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: systematic review from the Indian subcontinent. Acta Med Acad 2012;41(2):161–174. doi: 10.5644/ama2006-124.49Rajagopala S, Singh N. Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: systematic review from the Indian subcontinent. Acta Med Acad 2012;41(2):161–174. doi: 10.5644/ama2006-124.49Schram AM, Campigotto F, Mullally A, Fogerty A, Massarotti E, Neuberg D, Berliner N. Marked hyperferritinemia does not predict for HLH in the adult population. Blood 2015 Mar 5;125(10):1548–1552. doi: 10.1182/blood-2014-10-602607Schram AM, Campigotto F, Mullally A, Fogerty A, Massarotti E, Neuberg D, Berliner N. Marked hyperferritinemia does not predict for HLH in the adult population. Blood 2015 Mar 5;125(10):1548–1552. doi: 10.1182/blood-2014-10-602607Niller HH. Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): a putative role for Leptospira infection. A hypothesis. Acta Microbiol Immunol Hung 2010 Sep;57(3):181–189. doi: 10.1556/AMicr.57.2010.3.3Niller HH. Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): a putative role for Leptospira infection. A hypothesis. Acta Microbiol Immunol Hung 2010 Sep;57(3):181–189. doi: 10.1556/AMicr.57.2010.3.3Aulagnon F, Lapidus N, Canet E, Galicier L, Boutboul D, Peraldi MN, Reuter D, Bernard R, Schlemmer B, Azoulay E, Zafrani L. Acute kidney injury in adults with hemophagocytic lymphohistiocytosis. Am J Kidney Dis 2015 Jun;65(6):851–859. doi: 10.1053/j.ajkd.2014.10.012Aulagnon F, Lapidus N, Canet E, Galicier L, Boutboul D, Peraldi MN, Reuter D, Bernard R, Schlemmer B, Azoulay E, Zafrani L. Acute kidney injury in adults with hemophagocytic lymphohistiocytosis. Am J Kidney Dis 2015 Jun;65(6):851–859. doi: 10.1053/j.ajkd.2014.10.012Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol 2015 Mar;90(3):220–224. doi: 10.1002/ajh.23911Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol 2015 Mar;90(3):220–224. doi: 10.1002/ajh.23911Tseng YT, Sheng WH, Lin BH, Lin CW, Wang JT, Chen YC, Chang SC. Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults. J Microbiol Immunol Infect 2011 Jun;44(3):191– 197. doi: 10.1016/j.jmii.2011.01.027Tseng YT, Sheng WH, Lin BH, Lin CW, Wang JT, Chen YC, Chang SC. Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults. J Microbiol Immunol Infect 2011 Jun;44(3):191– 197. doi: 10.1016/j.jmii.2011.01.027Kapoor S, Morgan CK, Siddique MA, Guntupalli KK. Intensive care unit complications and outcomes of adult patients with hemophagocytic lymphohistiocytosis: A retrospective study of 16 cases. World J Crit Care Med 2018 Nov 30;7(6):73–83. doi: 10.5492/wjccm.v7.i6.73Kapoor S, Morgan CK, Siddique MA, Guntupalli KK. Intensive care unit complications and outcomes of adult patients with hemophagocytic lymphohistiocytosis: A retrospective study of 16 cases. World J Crit Care Med 2018 Nov 30;7(6):73–83. doi: 10.5492/wjccm.v7.i6.73Diack ND, Kane BS, Fall S, Sall A, Daher AK, Niasse M, Ndiaye N, Djiba B, Ndiaye FS, Leye A, Pouye A. Adult Hemophagocytic Lymphohistiocytosis in Sub-Saharan Area: A Retrospective Study of 26 cases. Cureus 2020 Mar 13;12(3):e7258. doi: 10.7759/cureus.7258Diack ND, Kane BS, Fall S, Sall A, Daher AK, Niasse M, Ndiaye N, Djiba B, Ndiaye FS, Leye A, Pouye A. Adult Hemophagocytic Lymphohistiocytosis in Sub-Saharan Area: A Retrospective Study of 26 cases. Cureus 2020 Mar 13;12(3):e7258. doi: 10.7759/cureus.7258Chen HS, Wu MS, Yen TS, Chen WY. Soluble interleukin-2 receptor in patients with glomerular diseases. Postgrad Med J 1995 Oct;71(840):617–622. doi: 10.1136/pgmj.71.840.617Chen HS, Wu MS, Yen TS, Chen WY. Soluble interleukin-2 receptor in patients with glomerular diseases. Postgrad Med J 1995 Oct;71(840):617–622. doi: 10.1136/pgmj.71.840.617Chen X, Li Y, Ding X, Zou J, Shen B, Liu Z, Lv W, Cao X, Xiang F. The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis. Ren Fail 2020 Nov;42(1):419–427. doi: 10.1080/0886022X.2020.1761388Chen X, Li Y, Ding X, Zou J, Shen B, Liu Z, Lv W, Cao X, Xiang F. The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis. Ren Fail 2020 Nov;42(1):419–427. doi: 10.1080/0886022X.2020.1761388Singh D, Raghunathan V, Dhaliwal M, Rastogi N, Chadha R, Yadav SP. Soluble interleukin-2 receptor level as a marker of hemophagocytic lymphohistiocytosis in children with dengue. Front Pediatr 2021; 9(721857):1–5. doi: 10.3389/fped.2021.721857Singh D, Raghunathan V, Dhaliwal M, Rastogi N, Chadha R, Yadav SP. Soluble interleukin-2 receptor level as a marker of hemophagocytic lymphohistiocytosis in children with dengue. Front Pediatr 2021; 9(721857):1–5. doi: 10.3389/fped.2021.721857

The authors declare that there are no conflicts of interest present.