spbmedicalrecordsНовые Санкт-Петербургские врачебные ведомостиNew St. Petersburg Medical Records1609-2201Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова10.24884/1609-2201-2024-103-2-34-41spbmedicalrecords-18Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSБиологические маркеры синдрома облитерирующего бронхиолита у реципиентов аллогенной трансплантации гемопоэтических стволовых клетокBiological markers of bronchiolitis obliterans syndrome in recipients of allogeneic hematopoietic stem cell transplantationhttps://orcid.org/0000-0003-4309-8186КулагинЕ. А.KulaginE. A.

Кулагин Егор Александрович, кандидат медицинских наук, ассистент кафедры терапии госпитальной с курсом аллергологии и иммунологии имени ак. М. В. Черноруцкого с клиникой, врач-пульмонолог клиники Научно-исследовательского института детской онкологии, гематологии и трансплантологии имени Р. М. Горбачевой

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, 6

Egor A. Kulagin, Cand. of Sci. (Med.), Assistant of Department of Hospital Therapy with a Course of Allergology and Immunology named after ac. M. V. Chernorutsky with clinic, pulmonologist, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation

Saint Petersburg, 194044

egordoc@mail.ruhttps://orcid.org/0000-0002-6430-6960ТрофимовВ. И.TrofimovV. I.

Трофимов Василий Иванович, доктор медицинских наук, профессор, Заслуженный деятель науки Российской Федерации, заведующий кафедрой терапии госпитальной с курсом аллергологии и иммунологии имени ак. М. В. Черноруцкого с клиникой

Санкт-Петербург

Vasiliy I. Trofimov, Dr. of Sci. (Med.), Professor, Honored Scientist of the Russian Federation, Department of Hospital Therapy with a Course of Allergology and Immunology named after ac. M. V. Chernorutsky with clinic

Saint Petersburg

trofvi@mail.ruПервый Санкт-Петербургский государственный медицинский университет имени академика И. П. ПавловаРоссияPavlov UniversityRussian Federation202401112024023441Copyright © Кулагин Е.А., Трофимов В.И., 20242024Кулагин Е.А., Трофимов В.И.Kulagin E.A., Trofimov V.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.docved.ru/jour/article/view/18

Синдром облитерирующего бронхиолита (СОБ) – редкое неинфекционное легочное осложнение аллогенной трансплантации гемопоэтических стволовых клеток (алло-ТГСК) или трансплантации легких. Ранняя диагностика СОБ требует новых подходов, в том числе поиска биологических маркеров легочного повреждения после алло-ТГСК. Целью настоящей работы является обзор литературных данных о биологических маркерах СОБ. Литературные данные о биомаркерах СОБ у реципиентов алло-ТГСК ограничены, необходимы дальнейшие исследования.

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) or lung transplantation. Early diagnosis of BOS requires new approaches including the search for biological markers of pulmonary damage after allo-HSCT. The aim of this work is to review literary data on biological markers of BOS. Conclusion. Literary data on biomarkers of BOS in allo-HSCT recipients are limited. Further research is needed.

синдром облитерирующего бронхиолитааллогенная трансплантация гемопоэтических стволовых клетокреакция «трансплантат против хозяина»биологические маркерыдиагностикаbronchiolitis obliterans syndromeallogeneic hematopoietic stem cell transplantationgraft versus host diseasebiological markersdiagnosisReferencesПульмонология. Национальное руководство. Краткое издание / под ред. А. Г. Чучалина. М. . P. ГЭОТАР-Медиа, 2020. 768 с. ISBN 978-5-9704-5323-0.A. G. Chuchalin, eds. Pulmonology. National guidelines. Moscow: GEOTAR-Media, 2020. 768 p. (In Russ.). ISBN 978-5-9704-5323-0.Barker A. F., Bergeron A., Rom W. N., Hertz M. I. Obliterative bronchiolitis // N. Engl. J. Med. 2014. Vol. 370, no. 19. P. 1820– 1828. DOI: 10.1056/NEJMra1204664.Barker A. F., Bergeron A., Rom W. N., Hertz M. I. Obliterative bronchiolitis. N. Engl. J. Med. 2014;370(19):1820–1828. DOI: 10.1056/NEJMra1204664.Кулагин Е. А., Волкова А. Г., Николаев И. Ю. и др. Частота, факторы риска и клиническая характеристика облитерирующего бронхиолита после аллогенной трансплантации гемопоэтических стволовых клеток // Пульмонология. 2022. Т. 32, № 1. С. 77–88. DOI: 10.18093/0869-0189-2022-32-1-77-88.Kulagin E. A., Volkova A. G., Nikolaev I. Yu. et al. Incidence, risk factors and clinical characteristics of bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. Pulmonologiya. 2022;32(1):77–88. (In Russ.). DOI: 10.18093/0869-0189-2022-32-1-77-88.Filipovich A. H., Weisdorf D., Pavletic S. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. P. I. Diagnosis and staging working group report // Biol Blood Marrow Transplant. 2005. Vol. 11, no. 12. P. 945–56. DOI: 10.1016/j.bbmt.2005.09.004.Filipovich A. H., Weisdorf D., Pavletic S. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease): I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56. DOI: 10.1016/j.bbmt.2005.09.004.Jagasia M. H., Greinix H. T., Arora M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. P. I. The 2014 Diagnosis and Staging Working Group report // Biol Blood Marrow Transplant. 2015. Vol. 21, no. 3. P. 389–401. DOI: 10.1016/j.bbmt.2014.12.001.Jagasia M. H., Greinix H. T., Arora M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389–401. DOI: 10.1016/j.bbmt.2014.12.001.Kitko C. L., Pidala J., Schoemans H. M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report // Transplant Cell Ther. 2021. Vol. 27, no. 7. P. 545–557. DOI: 10.1016/j.jtct.2021.03.033.Kitko C. L., Pidala J., Schoemans H. M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report. Transplant Cell Ther. 2021;27(7):545–557. DOI: 10.1016/j.jtct.2021.03.033.Glanville A. R., Benden C., Bergeron A. et al. Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions // ERJ Open Res. 2022. Vol. 8, no. 3. P. 00185–2022. DOI: 10.1183/23120541.00185-2022.Glanville A. R., Benden C., Bergeron A. et al. Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions. ERJ Open Res. 2022;8(3):00185–2022. DOI: 10.1183/23120541.00185-2022.Bos S., Murray J., Marchetti M. et al. ERS/EBMT clinical practice guidelines on treatment of pulmonary chronic graft-versus-host disease in adults // Eur Respir J. 2024. Vol. 63, no. 3. P. 2301727. DOI: 10.1183/13993003.01727-2023.Bos S., Murray J., Marchetti M. et al. ERS/EBMT clinical practice guidelines on treatment of pulmonary chronic graft-versus- host disease in adults. Eur Respir J. 2024;63(3):2301727. DOI: 10.1183/13993003.01727-2023.Boehler A., Estenne M. Post-transplant bronchiolitis obliterans // Eur Respir J. 2003. Vol. 22, no. 6. P. 1007–18. DOI: 10.1183/09031936.03.00039103.Boehler A., Estenne M. Post-transplant bronchiolitis obliterans. Eur Respir J. 2003;22(6):1007–18. DOI: 10.1183/09031936.03.00039103.Cooke K. R., Luznik L., Sarantopoulos S. et al. The Biology of Chronic Graft-versus-Host Disease. P. A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease // Biol Blood Marrow Transplant. 2017. Vol. 23, no. 2. P. 211–234. DOI: 10.1016/j.bbmt.2016.09.023.Cooke K. R., Luznik L., Sarantopoulos S. et al. The Biology of Chronic Graft-versus-Host Disease): A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017;23(2):211–234. DOI: 10.1016/j.bbmt.2016.09.023.Zeiser R., Blazar B. R. Pathophysiology of Chronic Graft-versusHost Disease and Therapeutic Targets // N Engl J Med. 2017. Vol. 377, no. 26. P. 2565–2579. DOI: 10.1056/NEJMra1703472.Zeiser R., Blazar B. R. Pathophysiology of Chronic Graft- versus-Host Disease and Therapeutic Targets. N Engl J Med. 2017;377(26):2565–2579. DOI: 10.1056/NEJMra1703472.Ghimire S., Weber D., Mavin E. et al. Pathophysiology of GvHD and Other HSCT-Related Major Complications // Front Immunol. 2017. Vol. 8. P. 79. DOI: 10.3389/fimmu.2017.00079.Ghimire S., Weber D., Mavin E. et al. Pathophysiology of GvHD and Other HSCT-Related Major Complications. Front Immunol. 2017;8:79. DOI: 10.3389/fimmu.2017.00079.Скворцова Ю., Новичкова Г., Масчан А. Новое в патогенезе, диагностике и лечении хронической реакции «трансплантат против хозяина» после аллогенной ТГСК // Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2018. Vol. 17, no. 2. P. 121–135. DOI: 10.24287/1726-1708-2018-17-2-121-135.Skvortsova Y. V., Novichkova G. A., Maschan A. A. New advances in pathogenesis, diagnostic and treatment of chronic graft-versus- host disease after allogeneic hematopoietic stem cell transplantation. Pediatric Hematology/Oncology and Immunopathology. 2018;17(2):121–135. (In Russ.). DOI: 10.24287/1726-1708-2018-17-2-121-135.Williams K. M., Inamoto Y., Im A. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. P. I. The 2020 Etiology and Prevention Working Group Report // Transplant Cell Ther. 2021. Vol. 27, no. 6. P. 452–466. DOI: 10.1016/j.jtct.2021.02.035.Williams K. M., Inamoto Y., Im A. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report. Transplant Cell Ther. 2021;27(6):452–466. DOI: 10.1016/j.jtct.2021.02.035.Wolff D., Greinix H., Lee S. J. et al. Biomarkers in chronic graftversus-host disease. P. quo vadis? // Bone Marrow Transplant. 2018. Vol. 53, no. 7. P. 832–837. DOI: 10.1038/s41409-018-0092-x.Wolff D., Greinix H., Lee S. J. et al. Biomarkers in chronic graft-versus-host disease: quo vadis? Bone Marrow Transplant. 2018;53(7):832–837. DOI: 10.1038/s41409-018-0092-x.Mattsson J., Remberger M., Andersson O. et al. Decreased serum levels of clara cell secretory protein (CC16) are associated with bronchiolitis obliterans and may permit early diagnosis in patients after allogeneic stem-cell transplantation // Transplantation. 2005. Vol. 79, no. 10. P. 1411–6. DOI: 10.1097/01.tp.0000158354.39635.ab.Mattsson J., Remberger M., Andersson O. et al. Decreased serum levels of clara cell secretory protein (CC16) are associated with bronchiolitis obliterans and may permit early diagnosis in patients after allogeneic stem-cell transplantation. Transplantation. 2005;79(10):1411–6. DOI: 10.1097/01.tp.0000158354.39635.ab.Hermans C., Bernard A. Lung epithelium-specific proteins: characteristics and potential applications as markers // Am J Respir Crit Care Med. 1999. Vol. 159, no. 2. P. 646–78. DOI: 10.1164/ajrccm.159.2.9806064.Hermans C., Bernard A. Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med. 1999;159(2):646–78. DOI: 10.1164/ajrccm.159.2.9806064.Dierynck I., Bernard A., Roels H., De Ley M. Potent inhibition of both human interferon-gamma production and biologic activity by the Clara cell protein CC16 // Am J Respir Cell Mol Biol. 1995. Vol. 12, no. 2. P. 205–10. DOI: 10.1165/ajrcmb.12.2.7865218.Dierynck I., Bernard A., Roels H., De Ley M. Potent inhibition of both human interferon-gamma production and biologic activity by the Clara cell protein CC16. Am J Respir Cell Mol Biol. 1995;12(2):205–10. DOI: 10.1165/ajrcmb.12.2.7865218.Lesur O., Bernard A., Arsalane K. et al. Clara cell protein , no. CC16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro // Am J Respir Crit Care Med. 1995. Vol. 152, no. 1. P. 290–7. DOI: 10.1164/ajrccm.152.1.7541278.Lesur O., Bernard A., Arsalane K. et al. Clara cell protein (CC- 16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro. Am J Respir Crit Care Med. 1995;152(1):290–7. DOI: 10.1164/ajrccm.152.1.7541278.Nakane T., Nakamae H., Kamoi H. et al. Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation // Bone Marrow Transplant. 2008. Vol. 42, no. 1. P. 43–9. DOI: 10.1038/bmt.2008.73.Nakane T., Nakamae H., Kamoi H. et al. Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;42(1):43–9. DOI: 10.1038/bmt.2008.73.Hartl D., Griese M. Surfactant protein D in human lung diseases // Eur J Clin Invest. 2006. Vol. 36, no. 6. P. 423–35. DOI: 10.1111/j.1365-2362.2006.01648.x.Hartl D., Griese M. Surfactant protein D in human lung diseases. Eur J Clin Invest. 2006;36(6):423–35. DOI: 10.1111/j.1365-2362.2006.01648.x.Zhang H., Chen L., Wu L. et al. Diagnostic and prognostic predictive values of circulating KL-6 for interstitial lung disease. P. A PRISMA-compliant systematic review and meta-analysis // Medicine (Baltimore). 2020. Vol. 99, no. 16. P. e19493. DOI: 10.1097/MD.0000000000019493.Zhang H., Chen L., Wu L. et al. Diagnostic and prognostic predictive values of circulating KL-6 for interstitial lung disease: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2020;99(16):e19493. DOI: 10.1097/MD.0000000000019493.Kuzmina Z., Greinix H. T., Weigl R. et al. Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia // Blood. 2011. Vol. 117, no. 7. P. 2265–74. DOI: 10.1182/blood-2010-07-295766.Kuzmina Z., Greinix H. T., Weigl R. et al. Significant differences in B-cell subpopulations characterize patients with chronic graft- versus-host disease-associated dysgammaglobulinemia. Blood. 2011;117(7):2265–74. DOI: 10.1182/blood-2010-07-295766.Carsetti R., Rosado M. M., Donnanno S. et al. The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency // J Allergy Clin Immunol. 2005. Vol. 115, no. 2. P. 412–7. DOI: 10.1016/j.jaci.2004.10.048.Carsetti R., Rosado M. M., Donnanno S. et al. The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency. J Allergy Clin Immunol. 2005;115(2):412–7. DOI: 10.1016/j.jaci.2004.10.048.Kainulainen L., Varpula M., Liippo K. et al. Pulmonary abnormalities in patients with primary hypogammaglobulinemia // J Allergy Clin Immunol. 1999. Vol. 104, no. 5. P. 1031–6. DOI: 10.1016/s0091-6749(99)70085-0.Kainulainen L., Varpula M., Liippo K. et al. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. JAllergy Clin Immunol. 1999;104(5):1031–6. DOI: 10.1016/s0091-6749(99)70085-0.Kuzmina Z., Krenn K., Petkov V. et al. CD19(+)CD21(low) B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome // Blood. 2013. Vol. 121, no. 10. P. 1886–95. DOI: 10.1182/blood-2012-06-435008.Kuzmina Z., Krenn K., Petkov V. et al. CD19(+)CD21(low) B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome. Blood. 2013;121(10):1886– 95. DOI: 10.1182/blood-2012-06-435008.Yamashita C. M., Dolgonos L., Zemans R. L. et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis // Am J Pathol. 2011. Vol. 179, no. 4. P. 1733–45. DOI: 10.1016/j.ajpath.2011.06.041.Yamashita C. M., Dolgonos L., Zemans R. L. et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am J Pathol. 2011;179(4):1733–45. DOI: 10.1016/j.ajpath.2011.06.041.Liu X., Yue Z., Yu J. et al. Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation // Am J Transplant. 2016. Vol. 16, no. 8. P. 2342–51. DOI: 10.1111/ajt.13750.Liu X., Yue Z., Yu J. et al. Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation. Am J Transplant. 2016;16(8):2342–51. DOI: 10.1111/ajt.13750.Inamoto Y., Martin P. J., Onstad L. E. et al. Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation // Transplant Cell Ther. 2021. Vol. 27, no. 9. P. 759.e1–759.e8. DOI: 10.1016/j.jtct.2021.06.006.Inamoto Y., Martin P. J., Onstad L. E. et al. Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021;27(9):759.e1–759.e8. DOI: 10.1016/j.jtct.2021.06.006.Yu J., Storer B. E., Kushekhar K. et al. Biomarker Panel for Chronic Graft-Versus-Host Disease // J Clin Oncol. 2016. Vol. 34, no. 22. P. 2583–90. DOI: 10.1200/JCO.2015.65.9615.Yu J., Storer B. E., Kushekhar K. et al. Biomarker Panel for Chronic Graft-Versus-Host Disease. J Clin Oncol. 2016;34(22):2583–90. DOI: 10.1200/JCO.2015.65.9615.Rosewich M., Zissler U. M., Kheiri T. et al. Airway inflammation in children and adolescents with bronchiolitis obliterans // Cytokine. 2015. Vol. 73, no. 1. P. 156–62. DOI: 10.1016/j.cyto.2014.10.026.Rosewich M., Zissler U. M., Kheiri T. et al. Airway inflammation in children and adolescents with bronchiolitis obliterans. Cytokine. 2015;73(1):156–62. DOI: 10.1016/j.cyto.2014.10.026.Koh Y. Y., Jung D. E., Koh J. Y. et al. Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis obliterans // Chest. 2007. Vol. 131, no. 5. P. 1454–60. DOI: 10.1378/chest.06-0188.Koh Y. Y., Jung D. E., Koh J. Y. et al. Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis obliterans. Chest. 2007;131(5):1454–60. DOI: 10.1378/chest.06-0188.Jerkic S. P., Michel F., Donath H. et al. Calprotectin as a New Sensitive Marker of Neutrophilic Inflammation in Patients with Bronchiolitis Obliterans // Mediators Inflamm. 2020. Vol. 2020. P. 4641585. DOI: 10.1155/2020/4641585.Jerkic S. P., Michel F., Donath H. et al. Calprotectin as a New Sensitive Marker of Neutrophilic Inflammation in Patients with Bronchiolitis Obliterans. Mediators Inflamm. 2020;2020:4641585. DOI: 10.1155/2020/4641585.Ostrin E. J, Rider N. L., Alousi A. M. et al. A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept // Immunohorizons. 2023. Vol. 7, no. 6. P. 421–430. DOI: 10.4049/immunohorizons.2300031.Ostrin E. J, Rider N. L., Alousi A. M. et al. A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus- Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept. Immunohorizons. 2023;7(6):421– 430. DOI: 10.4049/immunohorizons.2300031.Logan B. R., Fu D., Howard A. et al. Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death // J Clin Invest. 2023. Vol. 133, no. 15. P. e168575. DOI: 10.1172/JCI168575.Logan B. R., Fu D., Howard A. et al. Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death. J Clin Invest. 2023;133(15):e168575. DOI: 10.1172/JCI168575.Groom J. R., Luster A. D. CXCR3 ligands: redundant, collaborative and antagonistic functions // Immunol Cell Biol. 2011. Vol. 89, no. 2. P. 207–15. DOI: 10.1038/icb.2010.158.Groom J. R., Luster A. D. CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol. 2011;89(2):207–15. DOI: 10.1038/icb.2010.158.Macheda M. L., Stacker S. A. Importance of Wnt signaling in the tumor stroma microenvironment // Curr Cancer Drug Targets. 2008. Vol. 8, no. 6. P. 454–65. DOI: 10.2174/156800908785699324.Macheda M. L., Stacker S. A. Importance of Wnt signaling in the tumor stroma microenvironment. Curr Cancer Drug Targets. 2008;8(6):454–65. DOI: 10.2174/156800908785699324.Federico G., Meister M., Mathow D. et al. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis // JCI Insight. 2016. Vol. 1, no. 1. P. e84916. DOI: 10.1172/jci.insight.84916.Federico G., Meister M., Mathow D. et al. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight. 2016;1(1):e84916. DOI: 10.1172/jci.insight.84916.

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