The analysis of treatment of Immunoglobulin A-nephropathy
- Authors: Dobronravov V.A.1, Kochoyan Z.S.1, Muzhetskaya T.O.1, Lin D.I.1
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Affiliations:
- Pavlov First Saint Petersburg State Medical University
- Issue: Vol 92, No 6 (2020)
- Pages: 23-32
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/34978
- DOI: https://doi.org/10.26442/00403660.2020.06.000669
- ID: 34978
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Abstract
Aim. An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN).
Materials and methods. A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 34±12 years, men – 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate ≥50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods – matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34).
Results. All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.333–2.950) and remission (odds ratio 0.919; 95% CI 0.379–2.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria >2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ.
Conclusion. IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria >2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.
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##article.viewOnOriginalSite##About the authors
Vladimir A. Dobronravov
Pavlov First Saint Petersburg State Medical University
Author for correspondence.
Email: dobronravov@nephrolog.ru
ORCID iD: 0000-0002-7179-5520
д.м.н., проф., зам. дир. НИИ нефрологии, каф. пропедевтики внутренних болезней
Russian Federation, Saint-PetersburgZinaida Sh. Kochoyan
Pavlov First Saint Petersburg State Medical University
Email: dobronravov@nephrolog.ru
ORCID iD: 0000-0001-8433-876X
студентка лечебного фак-та
Russian Federation, Saint-PetersburgTatyana O. Muzhetskaya
Pavlov First Saint Petersburg State Medical University
Email: dobronravov@nephrolog.ru
ORCID iD: 0000-0002-2398-0449
врач-нефролог клиники НИИ нефрологии
Russian Federation, Saint-PetersburgDaria I. Lin
Pavlov First Saint Petersburg State Medical University
Email: dobronravov@nephrolog.ru
ORCID iD: 0000-0002-1953-637X
студентка лечебного фак-та
Russian Federation, Saint-PetersburgReferences
- Schena FP, Nistor I. Epidemiology of IgA Nephropathy: A Global Perspective. Semin Nephrol. 2018;38:435-42. doi: 1016/j.semnephrol. 2018.05.013
- Boyaka PN. Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems. J Immunol. 2017;199:9-16. doi: 10.4049/jimmunol. 1601775
- Muto M, Manfroi B, Suzuki H, et al. Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy. J Am Soc Nephrol. 2017;28(4):1227-38. doi: 10.1681/ASN.2016050496
- Reily C, Ueda H, Huang ZQ, et al. Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease. J Immunol Res. 2014. doi: 10.1155/2014/197548
- Hiki Y, Odani H, Takahashi M, et al. Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy. Kidney Int. 2001 Mar;59(3):1077-85. doi: 10.1046/j.1523-1755.2001.0590031077.x
- Tomana M, Novak J, Julian B, et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest. 1999 Jul;104(1):73-81. doi: 10.1172/JCI5535
- Robert T, Berthelot L, Cambier A, et al. Molecular Insights into the Pathogenesis of IgA Nephropathy. Trend Mol Med. 2015;12:762-75. doi: 10.1016/j.molmed.2015.10.003
- Ben Mkaddem S, Benhamou M, Monteiro RC. Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools. Front Immunol. 2019;10:1-12. doi: 10.3389/fimmu.2019.00811
- Wyatt RJ, Julian BA. IgA Nephropathy. N Engl J Med. 2013;368:2402-14. doi: 10.1056/NEJMra1206793
- Novak J, Tomana M, Matousovic K, et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int. 2005;67:504-13. doi: 10.1111/j.1523-1755.2005.67107.x
- Kiryluk K, Li Y, Sanna-Cherchi S, et al. Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis. PLOS Genet. 2012;8(6):e1002765. doi: 10.1371/journal.pgen.1002765
- Moriyama T, Tanaka K, Iwasaki C, et al. Prognosis in IgA Nephropathy: 30-Year Analysis of 1,012 Patients at a Single Center in Japan. PLOS ONE. 2014;9(3). doi: 10.1371/journal.pone.0091756
- Lee H, Kim DK, Oh KH, et al. Mortality of IgA Nephropathy Patients: A Single Center in Korea. Experience over 30 Years. PLoS ONE. 2012;7(12):e51225. doi: 10.1371/journal.pone.0051225
- Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2012;27:1479-85. doi: 10.1093/ndt/gfr527
- Coppo R, Troyanov S, Bellur S, et al. Validation of the Oxford classification of IgA-nephropathy in cohorts with different presentations and treatments. Kidney Int. 2014;86:828-36. doi: 10.1038/ki.2014.63
- Sevillano AM, Gutiérrez E, Yuste C, et al. Remission of Hematuria Improves Renal Survival in IgA Nephropathy. J Am Soc Nephrol. 2017;28(10):3089-99. doi: 10.1681/ASN.2017010108
- Soares MFS, Roberts ISD. Histologic Classification of IgA Nephropathy: Past, Present, and Future. Semin Nephrol. 2018;38:477-84. doi: 10.1016/j.semnephrol.2018.05.017
- Coppo R. Treatment of IgA nephropathy: Recent advances and prospects. Nephrol Ther. 2018;1:13-21. doi: 10.1016/j.nephro.2018.02.010
- Hotta O, Furuta T, Chiba S, et al. Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis. 2002;39:493-502. doi: 10.1053/ajkd.2002.31399
- Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant. 2003;18:1321-9. doi: 10.1093/ndt/gfg081
- McIntyre CW, Fluck RJ, Lambie SH. Steroid and cyclophosphamide therapy for IgA nephropathy associated with crescentic change: an effective treatment. Clin Nephrol. 2001;56:193-8.
- Tan L, Tang Y, Peng W, et al. Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in Chinese Patients with Advanced IgA Nephropathy. Kidney Blood Press Res. 2018;43:1333-43. doi: 10.1159/000492592
- Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy The TESTING Randomized Clinical Trial. JAMA. 2017;318:432-42. doi: 10.1001/jama.2017.9362
- Yang YZ, Chen P, Liu LJ, et al. Comparison of the effects of hydroxychloroquine and corticosteroid treatment on proteinuria in IgA nephropathy: a case-control study. BMC Nephrol. 2019;20:297. doi: 10.1186/s12882-019-1488-6
- Rauen T, Fitzner C, Eitner F, et al. Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy. J Am Soc Nephrol. 2018;29:317-25. doi: 10.1681/ASN.2017060713
- Hou JH, Le WB, Chen N, et al. Mycophenolate Mofetil Combined With Prednisone Versus Full-Dose Prednisone in IgA Nephropathy With Active Proliferative Lesions: A Randomized Controlled Trial. Am J Kidney Dis. 2017;69:788-95. doi: 10.1053/j.ajkd.2016.11.027
- Chen S, Qing Yin, Song Ren, et al. A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study. Sci Rep. 2018;8:13663. doi: 10.1038/s41598-018-31727-5
- Tatematsu M, Yasuda Y, Morita Y, et al. Complete remission within 2 years predicts a good prognosis after methylprednisolone pulse therapy in patients with IgA nephropathy. Clin Exp Nephrol. 2012;16:883-91. doi: 10.1007/s10157-012-0644-0
- Добронравов В.А., Мужецкая Т.О., Лин Д.И., Кочоян З.Ш. Иммуноглобулин А-нефропатия в российской популяции: клинико-морфологическая презентация и отдаленный прогноз. Нефрология. 2019;6:45-60 [Dobronravov VA, Muzhetskaya TO, Lin DI, Kochoyan ZSh. Immunoglobulin A-nephropathy in Russian population: clinical and morphological presentation and long-term prognosis. Nefrologija. 2019;6:45-60 (In Russ.)]. doi: 10.36485/1561-6274-2019-23-6-45-60
- Rosenbaum PR, Rubin DB. The Central Role of the Propensity Score in Observational Studies for Causal Effects. Biometrika. 1983;70(1):41-55. doi: 10.1093/biomet/70.1.41
- Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399-424. doi: 10.1080/00273171.2011.568786
- D’Agostino Jr RB. Propensity Score Methods for Bias Reduction in the Comparison of a Treatment to a Non-Randomized Control Group. Stat Med. 1998;17(19):2265-81. doi: 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>3.0.co;2-b
- Elze MC, Gregson J, Baber U, et al. Comparison of Propensity Score Methods and Covariate Adjustment: Evaluation in 4 Cardiovascular Studies. J Am Coll Cardiol. 2017;69(3):345-57. doi: 10.1016/j.jacc.2016.10.060
- Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25(1):1-21. doi: 10.1214/09-STS313
- Austin PC. Variance Estimation When Using Inverse Probability of Treatment Weighting (IPTW) With Survival Analysis. Stat Med. 2016;35(30):5642-55. doi: 10.1002/sim.7084
- Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242-58. doi: 10.1002/sim.5984
- Pozzi C, Andrulli S, Vecchio L, et al. Corticosteroid Effectiveness in IgA Nephropathy: Long-Term Results of a Randomized, Controlled Trial. J Am Soc Nephrol. 2004;15(1):157-63. doi: 10.1097/01.asn.0000103869.08096.4f
- Qian G, Zhang X, Xu W, et al. Efficacy and safety of glucocorticoids for patients with IgA nephropathy: A Meta-Analysis. Int Urol Nephrol. 2019;51(5):859-68. doi: 10.1007/s11255-019-02094-5
- Lin Y, Jia J, Guo Y, et al. Corticosteroid for IgA Nephropathy: Are They Really Therapeutic? Am J Nephrol. 2018;47(6):385-94. doi: 10.1159/000489580
- Cheng J, Zhang X, Zhang W, et al. Efficacy and Safety of Glucocorticoids Therapy for IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials. Am J Nephrol. 2009;30(4):315-22. doi: 10.1159/000226129
- Liu Y, Xiao J, Shi X, et al. Immunosuppressive Agents Versus Steroids in the Treatment of IgA Nephropathy-Induced Proteinuria: A Meta-Analysis. Exp Ther Med. 2016;11(1):49-56. doi: 10.3892/etm.2015.2860
- Tesar V, Troyanov S, Bellur S. Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study. J Am Soc Nephrol. 2015;26:1-11. doi: 10.1681/ASN.2014070697
- Duan J, Liu D, Duan G, Liu Z. Long term efficacy of tonsillectomy as a treatment in patients with IgA nephropathy: a meta-analysis. Int Urol Nephrol. 2017;49(1):103-12. doi: 10.1007/s11255-016-1432-7
- Wang Y, Chen J, Wang Y, et al. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant. 2011;26(6):1923-31. doi: 10.1093/ndt/gfq674
- Liu LL, Wang LN, Jiang Y, et al. Tonsillectomy for IgA Nephropathy: a meta-analysis. Am J Kidney Dis. 2015;65(1):80-7. doi: 10.1053/j.ajkd.2014.06.036
- Kovács T, Vas T, Kövesdy CP, et al. Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients. Int Urol Nephrol. 2014;46(11):2175-82. doi: 10.1007/s11255-014-0818-7
- Feehally J, Coppo R, Troyanov S. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron. 2015;132(1):15-24. doi: 10.1159/000441852
- Piccoli A, Codognotto M, Tabbi MG, et al. Influence of tonsillectomy on the progression of mesangioproliferative glomerulonephritis. Nephrol Dial Transplant. 2010;25(8):2583-9. doi: 10.1093/ndt/gfq107
- Hirano K, Matsuzaki K, Yasuda T, et al. Association Between Tonsillectomy and Outcomes in Patients With Immunoglobulin A Nephropathy. JAMA Netw Open. 2019;2(5):e194772. doi: 10.1001/jamanetworkopen.2019.4772
- Harabuchi Y, Takahara M. Recent advances in the immunological understanding of association between tonsil and immunoglobulin A nephropathy as a tonsil-induced autoimmune/inflammatory syndrome. Immun Inflamm Dis. 2019;7(2):86-93. doi: 10.1002/iid3.248
- Shen XH, Liang SS, Chen HM, et al. Reversal of Active Glomerular Lesions After Immunosuppressive Therapy in Patients With IgA Nephropathy: A Repeat-Biopsy Based Observation. J Nephrol. 2015;28(4):441-9. doi: 10.1007/s40620-014-0165-x
- Yang D, He L, Peng X, et al. The efficacy of tonsillectomy on clinical remission and relapse in patients with IgA nephropathy: a randomized controlled trial. Ren Fail. 2016;38(2):242-8. doi: 10.3109/0886022X.2015.1128251
- Kawamura T, Yoshimura M, Miyazaki Y. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol Dial Transplant. 2014;29(8):1546-53. doi: 10.1093/ndt/gfu020
- Song YH, Cai GY, Xiao YF, et al. Efficacy and safety of calcineurin inhibitor treatment for IgA nephropathy: a meta-analysis. BMC Nephrology. 2017;18:61. doi: 10.1186/s12882-017-0467-z
- Pozzi C, Andrulli S, Pani A, et al. Addition of Azathioprine to Corticosteroids Does Not Benefit Patients with IgA Nephropathy. J Am Soc Nephrol. 2010;21(10):1783-90. doi: 10.1681/ASN.20100101
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