原发性IgA肾病的治疗进展

doi:10.12114/j.issn.1007-9572.2021.00.156

摘要/Abstract

摘要： 原发性IgA肾病是最普遍的原发性肾小球肾炎，其病理特点为IgA沉积在肾小球系膜细胞区。随着对原发性IgA肾病的逐渐认识，发现其并不是一种良性肾脏疾病，大约在20年内，30%~40%的原发性IgA肾病发展至终末期肾病，需要肾脏替代治疗。因此，原发性IgA肾病需要有效精准的治疗延缓疾病进展。本文主要对原发性IgA肾病治疗的相关研究进行综述，发现目前支持治疗成为原发性IgA肾病的主要治疗方式，另外扁桃体切除、激素、免疫抑制剂等治疗方式在一定情况下也可以用于原发性IgA肾病的治疗，近年来又出现了多种新型治疗方法为原发性IgA肾病的治疗提供了更多选择。

关键词: 肾小球肾炎, IGA；治疗；综述

Abstract: Primary IgA nephropathy is the most common type of primary glomerulonephritis，with pathological features of mesangial deposition of IgA. With increasingly intensive understanding of primary IgA nephropathy，it is found that it is not a benign kidney disease. In about 20 years，30%-40% of primary IgA nephropathy develops into end-stage renal disease，requiring kidney replacement therapy. Therefore，primary IgA nephropathy needs effective and precise treatment to delay its progression. This article mainly reviews the advances in the treatment of primary IgA nephropathy：supportive therapy has become the main treatment. Besides，tonsillectomy，hormone therapy，immunosuppressive therapy and other treatments can be used under certain circumstances. Recently emerged treatments can also be used as treatment options for choice.

Key words: Glomerulonephritis, IGA；Therapy；Review

于柏松,刘冰. 原发性IgA肾病的治疗进展[J]. 中国全科医学, 2021, 24(23): 2985-2991. DOI: 10.12114/j.issn.1007-9572.2021.00.156.
YU Baisong,LIU Bing. Advances in the Treatment of Primary IgA Nephropathy[J]. Chinese General Practice, 2021, 24(23): 2985-2991. DOI: 10.12114/j.issn.1007-9572.2021.00.156.

参考文献

［1］PENFOLD R S，PRENDECKI M，MCADOO S，et al. Primary IgA nephropathy：current challenges and future prospects［J］. Int J Nephrol Renovasc Dis，2018，11：137-148. DOI：10.2147/IJNRD.S129227.
［2］MESTECKY J，NOVAK J，MOLDOVEANU Z，et al. IgA nephropathy enigma［J］. Clin Immunol，2016，172：72-77. DOI：10.1016/j.clim.2016.07.011.
［3］ROLLINO C，VISCHINI G，COPPO R. IgA nephropathy and infections［J］. J Nephrol，2016，29（4）：463-468. DOI：10.1007/s40620-016-0265-x.
［4］SAHA M K，JULIAN B A，NOVAK J，et al. Secondary IgA nephropathy［J］. Kidney Int，2018，94（4）：674-681. DOI：10.1016/j.kint.2018.02.030.
［5］SUZUKI T，MIYAZAKI Y，SHIMIZU A，et al. Sodium-sensitive variability of the antiproteinuric efficacy of RAS inhibitors in outpatients with IgA nephropathy［J］. Clin Nephrol，2009，72（4）：274-285. DOI：10.5414/cnp72274.
［6］WU C，WANG A Y，LI G，et al. Association of high body mass index with development of interstitial fibrosis in patients with IgA nephropathy［J］. BMC Nephrol，2018，19（1）：381. DOI：10.1186/s12882-018-1164-2.
［7］HUANG P P，SHU D H，SU Z，et al. Association between lifestyle，gender and risk for developing end-stage renal failure in IgA nephropathy：a case-control study within 10 years［J］. Ren Fail，2019，41（1）：914-920. DOI：10.1080/0886022X.2019.1635029.
［8］PISONI R L，BRAGG-GRESHAM J L，YOUNG E W，et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study（DOPPS）［J］. Am J Kidney Dis，2004，44（1）：94-111. DOI：10.1053/j.ajkd.2004.03.023.
［9］KRIPKE D F，GARFINKEL L，WINGARD D L，et al. Mortality associated with sleep duration and insomnia［J］. Arch Gen Psychiatry，2002，59（2）：131-136. DOI：10.1001/archpsyc.59.2.131.
［10］YU J H，HAN K，KIM N H，et al. U-shaped association between sleep duration and urinary albumin excretion in Korean adults：2011—2014 Korea National Health and Nutrition Examination Survey［J］. PLoS One，2018，13（2）：e0192980. DOI：10.1371/journal.pone.0192980.
［11］CHEUNGPASITPORN W，THONGPRAYOON C，GONZALEZ-SUAREZ M L. The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis［J］. Nephrol Dial Transplant，2017，32（6）：991-996. DOI：10.1093/ndt/gfw072.
［12］JI Y，YANG K，XIAO B，et al. Efficacy and safety of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker therapy for IgA nephropathy：a meta-analysis of randomized controlled trials［J］. J Cell Biochem，2019，120（3）：3689-3695. DOI：10.1002/jcb.27648.
［13］ZHAO Y，FAN H，BAO B Y. Efficacy and safety of renin-angiotensin aldosterone system inhibitor in patients with IgA nephropathy：a meta-analysis of randomized controlled trials［J］. Iran J Public Health，2019，48（9）：1577-1588.
［14］Chapter 10：immunoglobulin A nephropathy［J］. Kidney Int Suppl，2012，2（2）：209-217. DOI：10.1038/kisup.2012.23.
［15］GLASSOCK R J. Glomerular disease：targeted steroid therapy for IgA nephropathy［J］. Nat Rev Nephrol，2017，13（7）：390-392. DOI：10.1038/nrneph.2017.65.
［16］RASCHE F M，KELLER F，RASCHE W G，et al. Why，when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy？［J］. Clin Exp Immunol，2016，186（2）：115-133. DOI：10.1111/cei.12823.
［17］LIU X W，WANG B，LI L，et al. Comparison of the effects of valsartan plus activated vitamin D versus valsartan alone in IgA nephropathy with moderate proteinuria［J］. Int Urol Nephrol，2020，52（1）：129-136. DOI：10.1007/s11255-019-02329-5.
［18］DENG J，ZHENG X，XIE H，et al. Calcitriol in the treatment of IgA nephropathy with non-nephrotic range proteinuria：a meta-analysis of randomized controlled trials［J］. Clin Nephrol，2017，87（1）：21-27. DOI：10.5414/CN108915.
［19］LI H，YANG X，YAO G，et al. Triptolide inhibits tonsillar IgA production by upregulating FDC-SP in IgA nephropathy［J］. Histol Histopathol，2020，35（6）：599-608. DOI：10.14670/HH-18-190.
［20］YANG D Y，HE L Y，PENG X F，et al. The efficacy of tonsillectomy on clinical remission and relapse in patients with IgA nephropathy：a randomized controlled trial［J］. Ren Fail，2016，38（2）：242-248. DOI：10.3109/0886022X.2015.1128251.
［21］HIRANO K，MATSUZAKI K，YASUDA T，et al. Association between tonsillectomy and outcomes in patients with immunoglobulin A nephropathy［J］. JAMA Netw Open，2019，2（5）：e194772. DOI：10.1001/jamanetworkopen.2019.4772.
［22］HOTTA O，MIYAZAKI M，FURUTA T，et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy［J］. Am J Kidney Dis，2001，38（4）：736-743. DOI：10.1053/ajkd.2001.27690.
［23］KONDO N，MORIYAMA T，TACHIKAWA M，et al. Tonsillectomy plus steroid pulse therapy is the most effective treatment in adult patients with C-Grade I IgA nephropathy，and the weight of the extracted palatine tonsils and Yamamoto scale have no significant correlation with the effects of this treatment［J］. Auris Nasus Larynx，2019，46（5）：764-771. DOI：10.1016/j.anl.2019.01.003.
［24］KOHAGURA K，ARIMA H，MIYASATO H，et al. Add-on effect of angiotensin receptor blockade（candesartan）on clinical remission in active IgA nephropathy patients treated with steroid pulse therapy and tonsillectomy：a randomized，parallel-group comparison trial［J］. Kidney Blood Press Res，2018，43（3）：780-792. DOI：10.1159/000489914.
［25］KUMON S，MORIYAMA T，KAMIYAMA T，et al. The impact of tonsillectomy combined with steroid pulse therapy in patients with advanced IgA nephropathy and impaired renal function［J］. Clin Exp Nephrol，2020，24（4）：295-306. DOI：10.1007/s10157-019-01828-0.
［26］KATAFUCHI R，KAWAMURA T，JOH K，et al. Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy［J］. Clin Exp Nephrol，2016，20（2）：244-252. DOI：10.1007/s10157-015-1159-2.
［27］TAKADA D，HOSHINO J，FUJII T，et al. Association between renal outcome and the number of steroid pulse therapies after tonsillectomy in patients with IgA nephropathy［J］. Clin Exp Nephrol，2019，23（3）：335-341. DOI：10.1007/s10157-018-1642-7.
［28］FEEHALLY J，COPPO R，TROYANOV S，et al. Tonsillectomy in a european cohort of 1 147 patients with IgA nephropathy［J］. Nephron，2016，132（1）：15-24. DOI：10.1159/000441852.
［29］GHARAVI A G，KIRYLUK K，CHOI M，et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy［J］. Nat Genet，2011，43（4）：321-327. DOI：10.1038/ng.787.
［30］DUAN J Y，LIU D W，DUAN G C，et al. Long-term efficacy of tonsillectomy as a treatment in patients with IgA nephropathy：a meta-analysis［J］. Int Urol Nephrol，2017，49（1）：103-112. DOI：10.1007/s11255-016-1432-7.
［31］RAUEN T，EITNER F，FITZNER C，et al. Intensive supportive care plus immunosuppression in IgA nephropathy［J］. N Engl J Med，2015，373（23）：2225-2236. DOI：10.1056/NEJMoa1415463.
［32］LYU J，ZHANG H，WONG M G，et al. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy：the TESTING randomized clinical trial［J］. JAMA，2017，318（5）：432-442. DOI：10.1001/jama.2017.9362.
［33］TIAN L，SHAO X，XIE Y，et al. The long-term efficacy and safety of immunosuppressive therapy on the progression of IgA nephropathy：a meta-analysis of controlled clinical trials with more than 5-year follow-up［J］. Expert Opin Pharmacother，2015，16（8）：1137-1147. DOI：10.1517/14656566.2015.1038238.
［34］TAKAHARA M，NAGATO T，NOZAKI Y，et al. A proliferation-inducing ligand（APRIL）induced hyper-production of IgA from tonsillar mononuclear cells in patients with IgA nephropathy［J］. Cell Immunol，2019，341：103925. DOI：10.1016/j.cellimm.2019.103925.
［35］CAO Y，LU G，CHEN X，et al. BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF-κB signaling pathway in glomerular mesangial cells［J］. Mol Med Rep，2020，21（2）：795-805. DOI：10.3892/mmr.2019.10870.
［36］SAMY E，WAX S，HUARD B，et al. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases［J］. Int Rev Immunol，2017，36（1）：3-19. DOI：10.1080/08830185.2016.1276903.
［37］VIEIRA F G，PING Q，MORENO A J，et al. Guanabenz treatment accelerates disease in a mutant SOD1 mouse model of ALS［J］. PLoS One，2015，10（8）：e0135570. DOI：10.1371/journal.pone.0135570.
［38］BOYD J K，CHEUNG C K，MOLYNEUX K，et al. An update on the pathogenesis and treatment of IgA nephropathy［J］. Kidney Int，2012，81（9）：833-843. DOI：10.1038/ki.2011.501.
［39］LAFAYETTE R A，CANETTA P A，ROVIN B H，et al. A randomized，controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction［J］. J Am Soc Nephrol，2017，28（4）：1306-1313. DOI：10.1681/ASN.2016060640.
［40］HARTONO C，CHUNG M，PERLMAN A S，et al. Bortezomib for reduction of proteinuria in IgA nephropathy［J］. Kidney Int Rep，2018，3（4）：861-866. DOI：10.1016/j.ekir.2018.03.001.
［41］WYATT R J，JULIAN B A. IgA nephropathy［J］. N Engl J Med，2013，368（25）：2402-2414. DOI：10.1056/NEJMra1206793.
［42］LAI K N. Pathogenesis of IgA nephropathy［J］. Nat Rev Nephrol，2012，8（5）：275-283. DOI：10.1038/nrneph.2012.58.
［43］SMITH A C，MOLYNEUX K，FEEHALLY J，et al. O-glycosylation of serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy［J］. J Am Soc Nephrol，2006，17（12）：3520-3528. DOI：10.1681/ASN.2006060658.
［44］SUZUKI H，KIRYLUK K，NOVAK J，et al. The pathophysiology of IgA nephropathy［J］. J Am Soc Nephrol，2011，22（10）：1795-1803. DOI：10.1681/ASN.2011050464.
［45］TOMANA M，NOVAK J，JULIAN BA，et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies［J］. J Clin Invest，1999，104（1）：73-81. DOI：10.1172/JCI5535.
［46］YEO S C，LIEW A，BARRATT J. Emerging therapies in immunoglobulin A nephropathy［J］. Nephrology（Carlton），2015，20（11）：788-800. DOI：10.1111/nep.12527.
［47］FELLSTR?M B C，BARRATT J，COOK H，et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy（NEFIGAN）：a double-blind，randomised，placebo-controlled phase 2b trial［J］. Lancet，2017，389（10084）：2117-2127. DOI：10.1016/S0140-6736（17）30550-0.
［48］ISMAIL G，OBRISCA B，JURUBITA R，et al. Budesonide versus systemic corticosteroids in IgA Nephropathy：a retrospective，propensity-matched comparison［J］. Medicine（Baltimore），2020，99（26）：e21000. DOI：10.1097/MD.0000000000021000.
［49］ZAND L，CANETTA P，LAFAYETTE R，et al. An open-label pilot study of adrenocorticotrophic hormone in the treatment of IgA nephropathy at high risk of progression［J］. Kidney Int Rep，2020，5（1）：58-65. DOI：10.1016/j.ekir.2019.10.007.
［50］LIU L J，YANG Y Z，SHI S F，et al. Effects of hydroxychloroquine on proteinuria in IgA nephropathy：a randomized controlled trial［J］. Am J Kidney Dis，2019，74（1）：15-22. DOI：10.1053/j.ajkd.2019.01.026.
［51］GAO R T，WU W，WEN Y B，et al. Hydroxychloroquine alleviates persistent proteinuria in IgA nephropathy［J］. Int Urol Nephrol，2017，49（7）：1233-1241. DOI：10.1007/s11255-017-1574-2.
［52］YANG Y Z，LIU L J，SHI S F，et al. Effects of hydroxychloroquine on proteinuria in immunoglobulin A nephropathy［J］. Am J Nephrol，2018，47（3）：145-152. DOI：10.1159/000487330.
［53］YANG Y Z，CHEN P，LIU L J，et al. Comparison of the effects of hydroxychloroquine and corticosteroid treatment on proteinuria in IgA nephropathy：a case-control study［J］. BMC Nephrol，2019，20（1）：297. DOI：10.1186/s12882-019-1488-6.
［54］BAI L，LI H，LI J，et al. Immunosuppressive effect of artemisinin and hydroxychloroquine combination therapy on IgA nephropathy via regulating the differentiation of CD4+ T cell subsets in rats［J］. Int Immunopharmacol，2019，70：313-323. DOI：10.1016/j.intimp.2019.02.056.
［55］BAI L，LI J，LI H，et al. Renoprotective effects of artemisinin and hydroxychloroquine combination therapy on IgA nephropathy via suppressing NF-κB signaling and NLRP3 inflammasome activation by exosomes in rats［J］. Biochem Pharmacol，2019，169：113619. DOI：10.1016/j.bcp.2019.08.021.
［56］MEDJERAL-THOMAS N R，O'SHAUGHNESSY M M. Complement in IgA nephropathy：the role of complement in the pathogenesis，diagnosis，and future management of IgA nephropathy［J］. Adv Chronic Kidney Dis，2020，27（2）：111-119. DOI：10.1053/j.ackd.2019.12.004.
［57］FLOEGE J，DAHA M R. IgA nephropathy：new insights into the role of complement［J］. Kidney Int，2018，94（1）：16-18. DOI：10.1016/j.kint.2018.03.009.
［58］LAFAYETTE R A，ROVIN B H，REICH H N，et al. Safety，tolerability and efficacy of narsoplimab，a novel MASP-2 inhibitor for the treatment of IgA nephropathy［J］. Kidney Int Rep，2020，5（11）：2032-2041. DOI：10.1016/j.ekir.2020.08.003.
［59］CHEN Y Z，GAO Q，ZHAO X Z，et al. Meta-analysis of Tripterygium wilfordii Hook F in the immunosuppressive treatment of IgA nephropathy［J］. Intern Med，2010，49（19）：2049-2055. DOI：10.2169/internalmedicine.49.3704.
［60］LIANG S，JIN J，SHEN X，et al. Triptolide protects podocytes via autophagy in immunoglobulin A nephropathy［J］. Exp Ther Med，2018，16（3）：2275-2280. DOI：10.3892/etm.2018.6480.
［61］刘小燕，祁爱蓉，罗登贵，等. 雷公藤制剂生殖毒性及联用减毒研究进展［J］. 中国中医药信息杂志，2018，25（4）：133-135. DOI：10.3969/j.issn.1005-5304.2018.04.030.
LIU X Y，QI A R，LUO D G，et al. Research progress in reproductive toxicity and detoxification by combined use of tripterygium wilfordill hook［J］. Chinese Journal of Information on Traditional Chinese Medicine，2018，25（4）：133-135. DOI：10.3969/j.issn.1005-5304.2018.04.030.
［62］曾佳丽，姜雪，余瑾，等. 昆仙胶囊对IgA肾病大鼠的肾保护作用及系膜细胞增殖的影响［J］. 中国现代医生，2019，57（31）：38-42.
ZENG J L，JIANG X，YU J，et al. Renal protection effect of kunxian capsule on rat with IgA nephropathy and its influence on mesangial cell proliferation［J］. China Modern Doctor，2019，57（31）：38-42.
［63］LI P，LIN H，NI Z，et al. Efficacy and safety of Abelmoschus manihot for IgA nephropathy：a multicenter randomized clinical trial［J］. Phytomedicine，76：153231. DOI：10.1016/j.phymed.2020.153231.
［64］张楠，杨洪涛. 缬沙坦联合百令胶囊对IgA肾病患者尿蛋白、尿渗透压的影响及其临床安全性的研究［J］. 西部中医药，2016，29（10）：116-118. DOI：10.3969/j.issn.1004-6852.2016.10.039.
ZHANG N，YANG H T. Study on the influence of valsartan and bailing capsule on urine protein and urine osmotic pressure of patients with IgA nephropathy and its clinical safety［J］. Western Journal of Traditional Chinese Medicine，2016，29（10）：116-118. DOI：10.3969/j.issn.1004-6852.2016.10.039.
［65］LI S，LI J P. Treatment effects of Chinese medicine（Yi-Qi-Qing-Jie herbal compound）combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease （TCM-WINE）：study protocol for a randomized controlled trial［J］. Trials，2020，21（1）：31. DOI：10.1186/s13063-019-3989-9.

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[14]	鲁欢，汤水福，陈刚毅，苏保林，詹冬香，吴兴波，王超，罗月中*. 温阳利水方水提物缓解脾肾阳虚特发性膜性肾病患者血清致小鼠足细胞损伤的机制研究[J]. 中国全科医学, 2018, 21(15): 1862-1868.
[15]	鲁欢，汤水福，陈刚毅，苏保林，吴兴波，王超，涂海涛，罗月中. 血清抗M型磷脂酶A2受体抗体对成年人特发性膜性肾病诊治的指导作用[J]. 中国全科医学, 2016, 19(14): 1647-1652.