IgA肾病的治疗新进展
New Progress in the Treatment of IgA Nephropathy
DOI: 10.12677/ACM.2023.132318, PDF,    科研立项经费支持
作者: 鲜华明*, 谢席胜#:川北医学院第二临床学院(南充市中心医院)肾内科,四川 南充;慢性肾脏病基础与临床研究南充市重点实验室,四川 南充;南充市临床医学研究中心,四川 南充
关键词: IgA肾病治疗新进展IgA Nephropathy Treatment Progress
摘要: IgA肾病(IgA Nephropathy, IgAN)是全世界最常见的肾小球肾炎,临床和病理表现均有较高的异质性,其确切的发病机制迄今仍不明确。IgAN的治疗方案相对保守,需要探索的问题依然较多。随着相关研究的深入,生物靶向药物等的出现,给本病的治疗带来了更多的进步,本文就目前IgAN治疗的研究进展综述如下。
Abstract: IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. Its exact pathogene-sis is still unclear, and its clinical and pathological manifestations are highly heterogeneous. The treatment of IgAN is still relatively conservative. With the deepening of relevant research and the emergence of bio-targeted drugs, which have brought more benefits to patients, this article sum-marizes the current research progress of IgAN treatment as follows.
文章引用:鲜华明, 谢席胜. IgA肾病的治疗新进展[J]. 临床医学进展, 2023, 13(2): 2272-2285. https://doi.org/10.12677/ACM.2023.132318

参考文献

[1] Rajasekaran, A., Julian, B.A. and Rizk, D.V. (2021) IgA Nephropathy: An Interesting Autoimmune Kidney Disease. The American Journal of the Medical Sciences, 361, 176-194. [Google Scholar] [CrossRef] [PubMed]
[2] Pattrapornpisut, P., Avila-Casado, C. and Reich, H.N. (2021) IgA Nephropathy: Core Curriculum 2021. American Journal of Kidney Diseases, 78, 429-441. [Google Scholar] [CrossRef] [PubMed]
[3] Gutierrez, E., et al. (2012) Long-Term Outcomes of IgA Nephrop-athy Presenting with Minimal or No Proteinuria. Journal of the American Society of Nephrology, 23, 1753-1760. [Google Scholar] [CrossRef
[4] Suzuki, H., et al. (2011) The Pathophysiology of IgA Nephropathy. Journal of the American Society of Nephrology, 22, 1795-1803. [Google Scholar] [CrossRef
[5] Li, M., et al. (2020) Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heteroge-neity of Genetic Susceptibility for IgA Nephropathy. Journal of the American Society of Nephrology, 31, 2949- 2963. [Google Scholar] [CrossRef
[6] (2021) Kidney Disease: Improving Global Outcomes Glomerular Diseases Work, G. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Inter-national, 100, S1-S276.
[7] Wyatt, R.J., et al. (1998) Epidemiology of IgA Nephropathy in Central and Eastern Ken-tucky for the Period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy Databank Project. Journal of the American Society of Nephrology, 9, 853-858. [Google Scholar] [CrossRef
[8] Schena, F.P. (1990) A Retrospective Analysis of the Natural History of Primary IgA Nephropathy Worldwide. The American Journal of Medicine, 89, 209-215. [Google Scholar] [CrossRef] [PubMed]
[9] Shen, P., et al. (2006) Clinicopathological Characteristics and Outcome of Adult Patients with Hematuria and/or Proteinuria Found during Routine Examination. Nephron Clinical Practice, 103, c149-156. [Google Scholar] [CrossRef] [PubMed]
[10] Li, L.S. and Liu, Z.H. (2004) Epidemiologic Data of Renal Diseases from a Single Unit in China: Analysis Based on 13,519 Renal Biopsies. Kidney International, 66, 920-923. [Google Scholar] [CrossRef] [PubMed]
[11] Woo, K.T., et al. (2010) Global Evolutionary Trend of the Prevalence of Primary Glomerulonephritis over the Past Three Decades. Nephron Clinical Practice, 116, c337-346. [Google Scholar] [CrossRef] [PubMed]
[12] Kiryluk, K., et al. (2014) Discovery of New Risk Loci for IgA Nephropathy Implicates Genes Involved in Immunity against Intestinal Pathogens. Nature Genetics, 46, 1187-1196. [Google Scholar] [CrossRef] [PubMed]
[13] Saka, S., et al. (2015) Genome-Wide Association Study of IgA Nephropathy Using 23465 Microsatellite Markers in a Japanese Population. Journal of Human Genetics, 60, 573-580. [Google Scholar] [CrossRef] [PubMed]
[14] Feehally, J., et al. (2010) HLA Has Strongest Association with IgA Nephropathy in Genome-Wide Analysis. Journal of the American Society of Nephrology, 21, 1791-1797. [Google Scholar] [CrossRef
[15] Li, M., et al. (2015) Identification of New Susceptibility Loci for IgA Nephropathy in Han Chinese. Nature Communications, 6, 7270. [Google Scholar] [CrossRef] [PubMed]
[16] Suzuki, K., et al. (2003) Incidence of Latent Mesangial IgA Deposition in Renal Allograft Donors in Japan. Kidney International, 63, 2286-2294. [Google Scholar] [CrossRef] [PubMed]
[17] Gharavi, A.G., et al. (2008) Aberrant IgA1 Glycosylation Is Inherited in Familial and Sporadic IgA Nephropathy. Journal of the American Society of Nephrology, 19, 1008-1014. [Google Scholar] [CrossRef
[18] Suzuki, H., et al. (2009) Aberrantly Glycosylated IgA1 in IgA Nephropathy Patients Is Recognized by IgG Antibodies with Restricted Heterogeneity. The Journal of Clinical Investiga-tion, 119, 1668-1677. [Google Scholar] [CrossRef
[19] Zhang, W. and Lachmann, P.J. (1994) Glycosylation of IgA Is Required for Optimal Activation of the Alternative Complement Pathway by Immune Complexes. Immunology, 81, 137-141.
[20] Magistroni, R., D’Agati, V.D., Appel, G.B. and Kiryluk, K. (2015) New Developments in the Genetics, Pathogenesis, and Therapy of IgA Nephropathy. Kidney International, 88, 974-989. [Google Scholar] [CrossRef] [PubMed]
[21] Perše, M. and Večerić-Haler, Z. (2019) The Role of IgA in the Pathogen-esis of IgA Nephropathy. International Journal of Molecular Sciences, 20, 6199. [Google Scholar] [CrossRef] [PubMed]
[22] Julian, B.A., et al. (1985) Familial IgA Nephropathy. Evidence of an Inherited Mechanism of Disease. The New England Journal of Medicine, 312, 202-208. [Google Scholar] [CrossRef
[23] Scolari, F., et al. (1999) Familial Clustering of IgA Nephropathy: Further Evidence in an Italian Population. American Journal of Kidney Diseases, 33, 857-865. [Google Scholar] [CrossRef
[24] Paterson, A.D., et al. (2007) Genome-Wide Linkage Scan of a Large Family with IgA Nephropathy Localizes a Novel Susceptibility Locus to Chromosome 2q36. Journal of the American Society of Nephrology, 18, 2408-2415. [Google Scholar] [CrossRef
[25] Karnib, H.H., et al. (2007) Characterization of a Large Lebanese Family Segregating IgA Nephropathy. Nephrology Dialysis Transplantation, 22, 772-777. [Google Scholar] [CrossRef] [PubMed]
[26] Tsuboi, N., et al. (2011) Discordant Clinicopathological Features in Monozygotic Twins with IgA Nephropathy. Nephrology Dialysis Transplantation, 26, 4146-4148. [Google Scholar] [CrossRef] [PubMed]
[27] Schena, F.P., et al. (1993) Abnormalities of the IgA Immune System in Members of Unrelated Pedigrees from Patients with IgA Nephropathy. Clinical and Experimental Immunology, 92, 139-144. [Google Scholar] [CrossRef] [PubMed]
[28] Kiryluk, K., et al. (2011) Aberrant Glycosylation of IgA1 Is Inherited in both Pediatric IgA Nephropathy and Henoch- Schönlein Purpura Nephritis. Kidney International, 80, 79-87. [Google Scholar] [CrossRef] [PubMed]
[29] Feehally, J. and Barratt, J. (2015) The Genetics of IgA Nephropa-thy: An Overview from Western Countries. Kidney Diseases (Basel, Switzerland), 1, 33-41. [Google Scholar] [CrossRef] [PubMed]
[30] Coppo, R. (2015) The Intestine-Renal Connection in IgA Nephropathy. Nephrology Dialysis Transplantation, 30, 360-366. [Google Scholar] [CrossRef] [PubMed]
[31] Bunker, J.J. and Ben-delac, A. (2018) IgA Responses to Microbiota. Immunity, 49, 211-224. [Google Scholar] [CrossRef] [PubMed]
[32] Floege, J., Rauen, T. and Tang, S.C.W. (2021) Current Treat-ment of IgA Nephropathy. Seminars in Immunopathology, 43, 717-728. [Google Scholar] [CrossRef] [PubMed]
[33] Russo, D., et al. (2001) Coadministration of Losartan and Enal-april Exerts Additive Antiproteinuric Effect in IgA Nephropathy. American Journal of Kidney Diseases, 38, 18-25. [Google Scholar] [CrossRef] [PubMed]
[34] Lennartz, D.P., et al. (2020) Single versus Dual Blockade of the Renin-Angiotensin System in Patients with IgA Nephropathy. Journal of Nephrology, 33, 1231-1239. [Google Scholar] [CrossRef] [PubMed]
[35] Heerspink, H.J.L., et al. (2019) Atrasentan and Renal Events in Patients with Type 2 Diabetes and Chronic Kidney Disease (SONAR): A Double-Blind, Randomised, Place-bo-Controlled Trial. The Lancet, 393, 1937-1947. [Google Scholar] [CrossRef
[36] Kim, S.-G., et al. (2022) FC052: Atrasentan for the Treat-ment of IGA Nephropathy: Interim Results from the Affinity Study. Nephrology Dialysis Transplantation, 37, gfac107.004. [Google Scholar] [CrossRef
[37] Heerspink, H.J.L., Kosiborod, M., Inzucchi, S.E. and Cherney, D.Z.I. (2018) Renoprotective Effects of Sodium-Glucose Cotransporter-2 Inhibitors. Kidney International, 94, 26-39. [Google Scholar] [CrossRef] [PubMed]
[38] van Bommel, E.J.M., Muskiet, M.H.A., van Baar, M.J.B., et al. (2020) The Renal Hemodynamic Effects of the SGLT2 Inhibitor Dapagliflozin Are Caused by Post-Glomerular Vas-odilatation Rather than Pre-Glomerular Vasoconstriction in Metformin-Treated Patients with Type 2 Diabetes in the Ran-domized, Double-Blind RED Trial. Kidney International, 97, 202-212. [Google Scholar] [CrossRef] [PubMed]
[39] Wheeler, D.C., et al. (2021) Effects of Dapagliflozin on Major Ad-verse Kidney and Cardiovascular Events in Patients with Diabetic and Non-Diabetic Chronic Kidney Disease: A Prespec-ified Analysis from the DAPA-CKD Trial. The Lancet. Diabetes and Endocrinology, 9, 22-31. [Google Scholar] [CrossRef
[40] Cherney, D.Z.I., et al. (2020) Effects of the SGLT2 Inhibitor Dapagliflozin on Proteinuria in Non-Diabetic Patients with Chronic Kidney Disease (DIAMOND): A Randomised, Double-Blind, Crossover Trial. The Lancet. Diabetes and Endocrinology, 8, 582-593. [Google Scholar] [CrossRef
[41] Herrington, W.G., et al. (2022) Empagliflozin in Patients with Chronic Kidney Disease. The New England Journal of Medicine, 388, 117-127.
[42] Rauen, T., et al. (2015) Inten-sive Supportive Care plus Immunosuppression in IgA Nephropathy. The New England Journal of Medicine, 373, 2225-2236. [Google Scholar] [CrossRef
[43] Lunde Haaskjold, Y., Rivedal, M., Gjærde Lura, N., Bjorneklett, R. and Knoop, T. (2022) MO268: Use of Corticosteroids in a Norwegian Cohort of Patients with IGA Nephropathy and Rapid Progression to End-Stage Renal Disease. Nephrology Dialysis Transplantation, 37, gfac067.067. [Google Scholar] [CrossRef
[44] Fellström, B.C., et al. (2017) Targeted-Release Budesonide versus Placebo in Patients with IgA Nephropathy (NEFIGAN): A Double-Blind, Randomised, Place-bo-Controlled Phase 2b Trial. The Lancet, 389, 2117-2127. [Google Scholar] [CrossRef
[45] Barratt, J., et al. (2022) Results from Part A of the Mul-ti-Center, Double-Blind, Randomized, Placebo-Controlled NefIgArd Trial, Which Evaluated Targeted-Release Formula-tion of Budesonide for the Treatment of Primary Immunoglobulin A Nephropathy. Kidney International, 103, 391-402.
[46] Tang, S.C., et al. (2010) Long-Term Study of Mycophenolate Mofetil Treatment in IgA Nephropathy. Kidney International, 77, 543-549. [Google Scholar] [CrossRef] [PubMed]
[47] Hou, J.H., et al. (2017) Mycopheno-late Mofetil Combined with Prednisone versus Full-Dose Prednisone in IgA Nephropathy with Active Proliferative Le-sions: A Randomized Controlled Trial. American Journal of Kidney Diseases, 69, 788-795. [Google Scholar] [CrossRef] [PubMed]
[48] Chen, Y., Li, Y., Yang, S., Li, Y. and Liang, M. (2014) Efficacy and Safety of Mycophenolate Mofetil Treatment in IgA Nephropathy: A Systematic Review. BMC Nephrology, 15, 193. [Google Scholar] [CrossRef] [PubMed]
[49] Maes, B.D., et al. (2004) Mycophenolate Mofetil in IgA Nephrop-athy: Results of a 3-Year Prospective Placebo- Controlled Randomized Study. Kidney International, 65, 1842-1849. [Google Scholar] [CrossRef] [PubMed]
[50] Frisch, G., et al. (2005) Mycophenolate Mofetil (MMF) vs Placebo in Patients with Moderately Advanced IgA Nephropathy: A Double-Blind Randomized Controlled Trial. Neph-rology Dialysis Transplantation, 20, 2139-2145. [Google Scholar] [CrossRef] [PubMed]
[51] Costedoat-Chalumeau, N., Dunogué, B., Morel, N., Le Guern, V. and Guettrot-Imbert, G. (2014) Hydroxychloroquine: A Multifaceted Treatment in Lupus. Presse Medicale (Paris, France: 1983), 43, e167-e180. [Google Scholar] [CrossRef] [PubMed]
[52] Komissarov, K., Nizheharodava, D., Pilotovich, V. and Zafran-skaya, M. (2022) MO220: Comparison of the Effects of Hydroxychloroquine and Glucocorticosteroids on Immunologi-cal Parametrs in Patients with IGA Nephropathy. Nephrology Dialysis Transplantation, 37, gfac067.019. [Google Scholar] [CrossRef
[53] Gao, R., Wu, W., Wen, Y. and Li, X. (2017) Hydroxychloroquine Alleviates Persistent Proteinuria in IgA Nephropathy. International Urology and Nephrology, 49, 1233-1241. [Google Scholar] [CrossRef] [PubMed]
[54] Liu, L.J., et al. (2019) Effects of Hydroxychloroquine on Pro-teinuria in IgA Nephropathy: A Randomized Controlled Trial. American Journal of Kidney Diseases, 74, 15-22. [Google Scholar] [CrossRef] [PubMed]
[55] Evans, D.J., et al. (1973) Glomerular Deposition of Properdin in Henoch-Schönlein Syndrome and Idiopathic Focal Nephritis. British Medical Journal, 3, 326-328. [Google Scholar] [CrossRef] [PubMed]
[56] Tomino, Y. (1980) Complement System in IgA Nephropathy. The Tokai Journal of Experimental and Clinical Medicine, 5, 15-22.
[57] Wang, Z., et al. (2021) Complement Activation Is Associated with Crescents in IgA Nephropathy. Frontiers in Immunology, 12, Article ID: 676919. [Google Scholar] [CrossRef] [PubMed]
[58] Liu, M., et al. (2015) Implication of Urinary Complement Factor H in the Progression of Immunoglobulin A Nephropathy. PLOS ONE, 10, e0126812. [Google Scholar] [CrossRef] [PubMed]
[59] Samy, E., Wax, S., Huard, B., Hess, H. and Schneider, P. (2017) Targeting BAFF and APRIL in Systemic Lupus Erythematosus and Other Antibody-Associated Diseases. Inter-national Reviews of Immunology, 36, 3-19. [Google Scholar] [CrossRef] [PubMed]
[60] Fan, Y., Gao, D. and Zhang, Z. (2022) Telitacicept, A Novel Humanized, Recombinant TACI-Fc Fusion Protein, for the Treatment of Systemic Lupus Erythematosus. Drugs of To-day (Barcelona, Spain: 1998), 58, 23-32. [Google Scholar] [CrossRef] [PubMed]
[61] Barratt, J., et al. (2022) Randomized Phase II JANUS Study of Atacicept in Patients with IgA Nephropathy and Persistent Proteinuria. Kidney International Reports, 7, 1831-1841. [Google Scholar] [CrossRef] [PubMed]
[62] Barratt, J., et al. (2022) FC051: Atacicept Reduces Serum ANTI-GD-IGA1 Levels in IgAN Patients. Nephrology Dialysis Transplantation, 37, gfac107.003. [Google Scholar] [CrossRef
[63] Barratt, J., et al. (2022) MO212: Updated Interim Results of a Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of BION-1301 in Patients with IGA Nephropathy. Nephrology Dialysis Transplantation, 37, gfac067.011. [Google Scholar] [CrossRef