IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treatment options for patients with IgA nephropathy including the drugs currently under evaluation in randomized control trials. An early initiation of immunosupressive regimens in patients with IgA nephropathy at risk of progression should result in the slowing down of the progression of renal function to end stage renal disease.

1st Faculty of Medicine General University Hospital Department of Nephrology Charles University 128 08 Prague Czech Republic

Zobrazit více v PubMed

Moriyama T., Tanaka K., Iwasaki C., Oshima Y., Ochi A., Kataoka H., Itabashi M., Takei T., Uchida K., Nitta K. Prognosis in IgA nephropathy: 30-year analysis of 1012 patients at a single center in Japan. PLoS ONE. 2014;9:e91756. doi: 10.1371/journal.pone.0091756. PubMed DOI PMC

Wyatt R.J., Julian B.A. IgA nephropathy. N. Engl. J. Med. 2013;368:2402–2414. doi: 10.1056/NEJMra1206793. PubMed DOI

Cattran D.C., Coppo R., Cook H.T., Feehally J., Roberts I.S., Troyanov S., Alpers C.E., Amore A., Barratt J., Berthoux F., et al. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, The Oxford classification of IgA nephropathy: Rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76:534–545. doi: 10.1038/ki.2009.243. PubMed DOI

Coppo R., Troyanov S., Camilla R., Hogg R.J., Cattran D.C., Cook T.H., Feehally J., Roberts I.S.D., Amore A., Alpers C.E., et al. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. 2010;77:921–927. doi: 10.1038/ki.2010.43. PubMed DOI

Reich H.N., Troyanov S., Scholey J.W., Cattran D.C., Toronto Glomerulonephritis Registry Remission of proteinuria improves prognosis in IgA nephropathy. J. Am. Soc. Nephrol. 2007;18:3177–3183. doi: 10.1681/ASN.2007050526. PubMed DOI

Barbour S.J., Espino-Hernandez G., Reich H.N., Coppo R., Roberts I.S.D., Feehally J., Herzenberg A.M., Cattran D.C. Oxford Derivation, North American Validation and VALIGA Consortia, The MEST score provides earlier risk prediction in lgA nephropathy. Kidney Int. 2016;89:167–175. doi: 10.1038/ki.2015.322. PubMed DOI

Barbour S.J., Espino-Hernandez G., Reich H., Coppo R., Roberts I.S.D., Feehally J., Herzenberg A.M., Cattran D., Bavbek N., Cook T.M., et al. A multicenter study of the predictive value of crescents in IgA nephropathy. J. Am. Soc. Nephrol. 2017;28:691–701. PubMed PMC

Haas M., Verhave J.C., Liu Z.-H., Alpers C.E., Barratt J., Becker J.U., Cattran D., Cook H.T., Coppo R., Feehally J., et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 2012;8:e1002765. PubMed PMC

Kiryluk K., Li Y., Sanna-Cherchi S., Rohanizadegan M., Suzuki H., Eitner F., Snyder H.J., Choi M., Hou P., Scolari F., et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 2014;46:1187–1196. doi: 10.1038/ng.3118. PubMed DOI PMC

Tomana M., Matousovic K., Julian B.A., Radl J., Konecny K., Mestecky J. Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int. 1997;52:509–516. doi: 10.1038/ki.1997.361. PubMed DOI

Tomana M., Novak J., Julian B.A., Matousovic K., Konecny K., Mestecky J. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J. Clin. Investig. 1999;104:73–81. doi: 10.1172/JCI5535. PubMed DOI PMC

Novak J., Kafkova L.R., Suzuki H., Tomana M., Matousovic K., Brown R., Hall S., Sanders J.T., Eison T.M., Moldoveanu Z., et al. IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol. Dial Transpl. 2011;26:3451–3457. doi: 10.1093/ndt/gfr448. PubMed DOI PMC

Maillard N., Wyatt R.J., Julian B.A., Kiryluk K., Gharavi A., Fremeaux-Bacchi V., Novak J. Current understanding of the role of complement in IgA nephropathy. J. Am. Soc. Nephrol. 2015;26:1503–1512. doi: 10.1681/ASN.2014101000. PubMed DOI PMC

Schmitt R., Stahl A.L., Olin A., Kristoffersson A.Ch., Rebetz J., Novak J., Lindahl G., Karpman D. The combined role of galactose-deficient IgA1 and streptococcal IgA-binding M protein in inducing IL-6 and C3 secretion from human mesangial cells: Implications for IgA nephropathy. J. Immunol. 2014;193:317–326. doi: 10.4049/jimmunol.1302249. PubMed DOI PMC

Lai K.N., Leung J.C.K., Chan L.Y.Y., Saleem M.A., Mathieson P.W., Lai F.M., Tang S.C.W. Activation of podocytes by mesangial-derived TNF-alpha: Glomerulo-podocytic communication in IgA nephropathy. Am. J. Physiol. Renal Physiol. 2008;294:F945–F955. doi: 10.1152/ajprenal.00423.2007. PubMed DOI

KDIGO KDIGO clinical practice guideline for glomerulonephritis. Kidney Int. 2012;2:139–274.

Coppo R. The gut-kidney axis in IgA nephropathy: Role of microbiota and diet on genetic predisposition. Pediatr. Nephrol. 2018;33:53–61. doi: 10.1007/s00467-017-3652-1. PubMed DOI

Monteiro R.C. Recent advances in the physiopathology of IgA nephropathy. Nephrol. Ther. 2018;14(Suppl. 1):S1–S8. doi: 10.1016/j.nephro.2018.02.004. PubMed DOI

Papista C., Lechner S., Mkaddem S.B., LeStang M.B., Abbad L., Bex-Coudrat J., Pillebout E., Chemouny J.M., Jablonski M., Flamant M., et al. Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction. Kidney Int. 2015;88:276–285. doi: 10.1038/ki.2015.94. PubMed DOI

Koulouridis E., Koulouridis I. Is the dietary protein restriction achievable in chronic kidney disease? The impact upon quality of life and the dialysis delay. Hippokratia. 2011;15(Suppl. 1):3–7. PubMed PMC

Konishi Y., Okada N., Okamura M., Morikawa T., Okumura M., Yoshioka K., Imanishi M. Sodium sensitivity of blood pressure appearing before hypertension and related to histological damage in immunoglobulin a nephropathy. Hypertension. 2001;38:81–85. doi: 10.1161/01.HYP.38.1.81. PubMed DOI

Suzuki T., Miyazaki Y., Shimizu A., Ito Y., Okonogi H., Ogura M. Sodium-sensitive variability of the antiproteinuric efficacy of RAS inhibitors in outpatients with IgA nephropathy. Clin. Nephrol. 2009;72:274–285. doi: 10.5414/CNP72274. PubMed DOI

Ouyang Y., Xie J., Yang M., Zhang X., Ren H., Wang W., Chen N. Underweight is an independent risk factor for renal function deterioration in patients with IgA nephropathy. PLoS ONE. 2016;11:e0162044. doi: 10.1371/journal.pone.0162044. PubMed DOI PMC

Shimamoto M., Ohsawa I., Suzuki H., Hisada A., Nagamachi S., Honda D., Inoshita H., Shimizu Y. Impact of Body Mass Index on progression of IgA nephropathy among Japanese patients. J. Clin. Lab. Anal. 2015;29:353–360. doi: 10.1002/jcla.21778. PubMed DOI PMC

Kittiskulnam P., Kanjanabuch T., Tangmanjitjaroen K., Chancharoenthana W., Praditpornsilpa K., Eiam-Ong S. The beneficial effects of weight reduction in overweight patients with chronic proteinuric immunoglobulin a nephropathy: A randomized controlled trial. J. Ren. Nutr. 2014;24:200–207. doi: 10.1053/j.jrn.2014.01.016. PubMed DOI

Cha Y.J., Lim B.J., Kim B.S., Kim Y., Yoo T.H., Han S.H., Kang S.W., Choi K.H. Smoking-related renal histologic injury in IgA nephropathy patients. Yonsei Med. J. 2016;57:209–216. doi: 10.3349/ymj.2016.57.1.209. PubMed DOI PMC

Ponticelli C., Glassock R.J. IgA Nephritis with Declining Renal Function: Treatment with Corticosteroids May Be Worthwhile. J. Am. Soc. Nephrol. 2015;26:2071–2073. doi: 10.1681/ASN.2015010030. PubMed DOI PMC

Sharma P., Blackburn R.C., Parke C.L., McCullough K., Marks A., Black C. Angiotension-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3)non-diabetic chronic kidney disease. Cochrane Database Syst. Rev. 2011;10:CD007751. PubMed

Jarrick S., Lundberg S., Welander A., Carrero J.J., Höijer J., Bottai M., Ludvigsson J.F. Mortality in IgA nephropathy: A nationwide population-based cohort study. J. Am. Soc. Nephrol. 2019;30:866–876. doi: 10.1681/ASN.2018101017. PubMed DOI PMC

Pozzi C., Andrulli S., Del Vecchio L., Melis P., Fogazzi G.B., Altieri P., Ponticelli C., Locatelli F. Corticosteroid effectiveness in IgA nephropathy: Long-term results of a randomized, controlled trial. J. Am. Soc. Nephrol. 2004;15:157–163. doi: 10.1097/01.ASN.0000103869.08096.4F. PubMed DOI

Lv J., Xu D., Perkovic V., Ma X., Johnson D.W., Woodward M., Levin A., Zhang H. TESTING Study Group. Corticosteroid therapy in IgA nephropathy. J. Am. Soc. Nephrol. 2012;23:1108–1116. doi: 10.1681/ASN.2011111112. PubMed DOI PMC

Tesar V., Troyanov S., Bellur S., Verhave J.C., Cook H.T., Feehally J., Roberts I.S.D., Cattran D. VALIGA study of the ERA-EDTA Immunonephrology Working Group. Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study. J. Am. Soc. Nephrol. 2015;26:2248–2258. doi: 10.1681/ASN.2014070697. PubMed DOI PMC

Lv J., Zhang H., Wong M.G., Jardine M.J., Hladunewich M., Jha V., Monaghan H., Zhao M. TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017;318:432–442. doi: 10.1001/jama.2017.9362. PubMed DOI PMC

Floege J., Barbour S.J., Cattran D.C., Hogan J.J., Nachman P.H., Tang S.C.W., Wetzels J.F.M. Management and treatment of glomerular diseases (part 1): Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019;95:268–280. doi: 10.1016/j.kint.2018.10.018. PubMed DOI

Rauen T., Eitner F., Fitzner C., Sommerer C., Zeier M., Otte B., Panzer U., Peters H. STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N. Engl. J. Med. 2015;373:2225–2236. doi: 10.1056/NEJMoa1415463. PubMed DOI

Rauen T., Wied S., Fitzner C., Eitner F., Sommerer C., Zeier M., Otte B., Panzer U. After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy. Kidney Int. 2020;98:1044–1052. doi: 10.1016/j.kint.2020.04.046. PubMed DOI

Fellström B.C., Barratt J., Cook H., Coppo R., Feehally J., de Fijter J.W., Floege J., Hetzel G. NEFIGAN Trial Investigators. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): A double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017;389:2117–2127. doi: 10.1016/S0140-6736(17)30550-0. PubMed DOI

Lechner S.M., Abbad L., Boedec E., Papista C., LeStang M.B., Moal C., Maillard J., Jamin A., Bex-Coudrat J., Wang Y., et al. IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA Nephropathy. J. Am. Soc. Nephrol. 2016;27:2622–2629. doi: 10.1681/ASN.2015080856. PubMed DOI PMC

Berthelot L., Papista C., Maciel T.T., Biarnes-Pelicot M., Tissandie E., Wang P.H.M., Tamouza H., Jamin A., Bex-Coudrat J., Gestin A., et al. Transglutaminase is essential for IgA nephropathy development acting through IgA receptors. J. Exp. Med. 2012;209:793–806. doi: 10.1084/jem.20112005. PubMed DOI PMC

Heerspink H.J.L., Stefánsson B.V., Correa-Rotter R., Chertow G.M., Greene T., Hou F.F., Mann J.F.E., McMurray J.J.V., Lindberg M., Rossing P., et al. Dapagliflozin in Patients with Chronic Kidney Disease. N. Engl. J. Med. 2020;383:1436–1446. doi: 10.1056/NEJMoa2024816. PubMed DOI

Roberts I.S., Cook H.T., Troyanov S., Alpers C.E., Amore A., Barratt J., Berthoux F., Bonsib S., Bruijn J.A., Cattran D.C., et al. The Oxford classification of IgA nephropathy: Pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–556. doi: 10.1038/ki.2009.168. PubMed DOI

Trimarchi H., Barratt J., Cattran D.C., Cook H.T., Coppo R., Haas M., Liu Z.H., Roberts I.S., Yuzawa Y., Zhank H., et al. Oxford classification of IgA nephropathy 2016: An update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91:1014–1021. doi: 10.1016/j.kint.2017.02.003. PubMed DOI

Coppo R. Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis. Nephrol. Dial Transpl. 2019;34:1832–1838. doi: 10.1093/ndt/gfy338. PubMed DOI

Barbour S.J., Coppo R., Zhang H., Liu Z.H., Suzuki Y., Matsuzaki K., Katafuchi R., Er L., Espino-Hernandez G., Kim S.J., et al. Evaluating a new international risk-prediction tool in IgA nephropathy. JAMA Int. Med. 2019;179:942–952. doi: 10.1001/jamainternmed.2019.0600. PubMed DOI PMC

Barbour S.J., Canney M., Coppo R., Zhang H., Liu Z.H., Suzuki Y., Matsuzaki K., Katafuchi R., Induruwage D., Er L., et al. Improving treatment decisions using personalized risk assessment from the international IgA nephropathy prediction tool. Kidney Int. 2020;98:1009–1019. doi: 10.1016/j.kint.2020.04.042. PubMed DOI

Sarcina C., Tinelli C., Ferrario F., Pani A., De Silvestri A., Scaini P., De Silvestri A., Scaini P., Del Vecchio L., Alberghini E., et al. Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy. Clin. J. Am. Soc. Nephrol. 2016;11:973–981. doi: 10.2215/CJN.02300215. PubMed DOI PMC

Pozzi C., Andrulli S., Pani A., Scaini P., Del Vecchio L., Fogazzi G., Vogt B., Cristofaro V.D., Allegri L., Cirami L., et al. Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J. Am. Soc. Nephrol. 2010;21:1783–1790. doi: 10.1681/ASN.2010010117. PubMed DOI PMC

Liu H., Xu X., Fang Y., Ji J., Zhang X., Yuan M., Liu C., Ding X. Comparison of glucocorticoids alone and combined with cyclosporine a in patients with IgA nephropathy: A prospective randomized controlled trial. Intern Med. 2014;53:675–681. doi: 10.2169/internalmedicine.53.1136. PubMed DOI

Xu L., Liu Z.C., Guan G.J., Lv X.A., Luo Q. Cyclosporine A combined with medium/low dose prednisone in progressive IgA nephropathy. Kaohsiung J. Med. Sci. 2014;30:390–395. doi: 10.1016/j.kjms.2014.04.002. PubMed DOI

Hou J.H., Le W.B., Chen N., Wang W.M., Liu Z.S., Liu D., Chen J.H., Tian J., Fu P., Hu Z.X., 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;69:788–795. doi: 10.1053/j.ajkd.2016.11.027. PubMed DOI

Tang S.C., Tang A.W., Wong S.S., Leung J.C., Ho Y.W., Lai K.N. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 2010;77:543–549. doi: 10.1038/ki.2009.499. PubMed DOI

Hogg R.J., Bay R.C., Jennette J.C., Sibley R., Kumar S., Fervenza F.C., Appel G., Cattran D., Fischer D., Hurley R.M., et al. Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy. Am. J. Kidney Dis. 2015;66:783–791. doi: 10.1053/j.ajkd.2015.06.013. PubMed DOI

Beckwith H., Medjeral-Thomas N., Galliford J., Griffith M., Levy J., Lightstone L., Palmer A., Roufosse C., Pusey C., Cook H.T., et al. Mycophenolate mofetil therapy in immunoglobulin a nephropathy: Histological changes after treatment. Nephrol. Dial Transpl. 2017;32:123–128. doi: 10.1093/ndt/gfw326. PubMed DOI

Liu D., Liu Y., Chen G., He L., Tang C., Wang C., Yang D., Li H., Dong Z., Liu H. Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy. Am. J. Nephrol. 2017;45:293–300. doi: 10.1159/000456039. PubMed DOI

Liu L.J., Yang Y.Z., Shi S.F., Bao Y.F., Yang C., Zhu S.N., Sui G.L., Chen Y.Q., Lv J.C., Zhang H. Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. Am. J. Kidney Dis. 2019;74:15–22. doi: 10.1053/j.ajkd.2019.01.026. PubMed DOI

Donadio J.V., Jr. Use of fish oil to treat patients with immunoglobulin a nephropathy. Am. J. Clin. Nutr. 2000;71:373S–375S. doi: 10.1093/ajcn/71.1.373s. PubMed DOI

Bomback A.S., Canetta P.A., Beck L.H., Jr., Ayalon R., Radhakrhisnan J., Appel G.B. Treatment of resistant glomerular diseases with adrenocorticotropic hormon gel: A prospective trial. Am. J. Nephrol. 2012;36:58–67. doi: 10.1159/000339287. PubMed DOI

Zand L., Canetta P., Lafayette R., Aslam N., Novak J., Sethi S., Fervenza C.F. An open-label pilot study of adrenocorticotrophic hormone in the treatment of IgA nephropathy at high risk of progression. KI Rep. 2020;5:58–65. doi: 10.1016/j.ekir.2019.10.007. PubMed DOI PMC

Zand L., Canetta P., Lafayette R., Aslam N., Jan N., Sethi S., Fervenza F.C. Tonsillectomy for IgA nephropathy: A meta-analysis. Am. J. Kidney Dis. 2015;65:80–87. PubMed

Kawamura T., Yoshimura M., Miyazaki Y., Okamoto H., Kimura K., Hirano K., Matsushima M., Utsunomiya Y., Ogura M., Yokoo T., et al. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin a nephropathy. Nephrol. Dial Transpl. 2014;29:1546–1553. doi: 10.1093/ndt/gfu020. PubMed DOI PMC

Feehally J., Coppo R., Troyanov S., Bellur S.S., Cattran D., Cook T., Roberts I.S.D., Verhave J.C., Camilla R., Vergano L., et al. VALIGA study of ERA-EDTA Immunonephrology Working Group. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron. 2016;132:15–24. doi: 10.1159/000441852. PubMed DOI

Lafayette R.A., Canetta P.A., Rovin B.H., Appel G.B., Novak J., Nath K.A., Sethi S., Tumlin J.A., Mehta K., Hogan M., et al. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J. Am. Soc. Nephrol. 2017;28:1306–1313. doi: 10.1681/ASN.2016060640. PubMed DOI PMC

Sugiura H., Takei T., Itabashi M., Tsukada M., Moriyama T., Kojima C., Shiohira T., Shimizu A., Tsuruta Y., Amemiya N., et al. Effect of single-dose rituximab on primary glomerular diseases. Nephron Clin. Pract. 2011;117:98–105. doi: 10.1159/000319656. PubMed DOI

Coppo R., Peruzzi L., Loiacono E., Bergallo M., Krutova A., Russo M.L., Cocchi E., Amore A., Lundberg S., Maixnerova D., et al. Defective gene expression of the membrane complement inhibitor CD46 in patients with progressive immunoglobulin A nephropathy. Nephrol. Dial Transpl. 2018;34:587–596. doi: 10.1093/ndt/gfy064. PubMed DOI

Espinosa M., Ortega R., Sánchez M., Segarra A., Salcedo M.T., González F., Camacho R., Valdivia M.A., Cabrera R., López K., et al. Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin. J. Am. Soc. Nephrol. 2014;9:897–904. doi: 10.2215/CJN.09710913. PubMed DOI PMC

Zhu L., Zhai Y.L., Wang F.M., Hou P., Lv J.Ch., Xu D.M., Shi S.F., Liu L.J., Yu F., Zhao M.H., et al. Variants in complement factor H and complement factor H-related protein genes, CFHR 3 and CFHR1, affect complement activation in IgA nephropathy. J. Am. Soc. Nephrol. 2015;26:1195–1204. doi: 10.1681/ASN.2014010096. PubMed DOI PMC

Xie J., Kiryluk K., Li Y., Mladkova N., Zhu L., Hou P., Ren H., Wang W., Zhang H., Chen N., et al. Fine mapping implicates a deletion of CFHR1 nad CFHR3 in protection from IgA nephropathy in Han Chinese. J. Am. Soc. Nephrol. 2016;27:3187–3194. doi: 10.1681/ASN.2015111210. PubMed DOI PMC

Jullien P., Laurent B., Claisse G., Masson I., Dinic M., Thibaudin D., Berthoux F., Alamartine E., Mariat C., Maillard N., et al. Deletion variants of CFHR1 and CFHR3 associate with mesangial immune deposits but not with progression of IgA nephropathy. J. Am. Soc. Nephrol. 2018;29:661–669. doi: 10.1681/ASN.2017010019. PubMed DOI PMC

Daha M.R., van Kooten C. Role of complement in IgA nephropathy. J. Nephrol. 2016;29:1–4. doi: 10.1007/s40620-015-0245-6. PubMed DOI PMC

Block G.A., Whitaker S. Maintenance of remission following completion of OMS721 treatment in patients with IgA nephropathy (IGAN). Abstract SA-PO278. J. Am. Soc. Nephrol. 2017;28:749–750.

Liu L., Zhan Y., Duan X., Peng Q., Liu Q., Zhou Y., Quan S., Xing G. C3a, C5a renal expression and their receptors are correlated to severity of IgA nephropathy. J. Clin. Immunol. 2014;34:224–232. doi: 10.1007/s10875-013-9970-6. PubMed DOI

ChemoCentryx . ClinicalTrials.gov [Internet] National library of Medicine; Bethesda, MD, USA: 2015. [(accessed on 20 December 2016)]. Open-Label Study to Evaluate Safety and Efficacy of CCX168 in Subjects With Immunoglobulin A Nephropathy on Stable RAAS Blockade. Available online: https://www.clinicaltrials.gov/ct2/show/NCT02384317.

Jayne D.R.W., Bruchfeld A.N., Harper L., Schaier M., Venning M.C., Hamilton P., Burst V., Grundmann F., Jadoul M., Szombati I., et al. Randomized trial of C5a receptor inhibitor Avacopan in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 2017;28:2756–2767. doi: 10.1681/ASN.2016111179. PubMed DOI PMC

Selvaskandan H., Cheung C.K., Muto M., Barratt J. New strategies and perspectives on managing IgA nephropathy. Clin. Exp. Nephrol. 2019;23:577–588. doi: 10.1007/s10157-019-01700-1. PubMed DOI PMC

Nakayamada S., Tanaka Y. BAFF- and APRIL targeted therapy in systemic autoimmune diseases. Inflamm Regen. 2016;36:1–6. doi: 10.1186/s41232-016-0015-4. PubMed DOI PMC

Lafayette R.A., Kelepouris E. Immunoglobulin A nephropathy: Advances in understanding of pathogenesis and treatment. Am. J. Nephrol. 2018;47:43–53. doi: 10.1159/000481636. PubMed DOI

Coppo R. Biomarkers and targeted new therapies for IgA nephropathy. Pediatr. Nephrol. 2017;32:725–731. doi: 10.1007/s00467-016-3390-9. PubMed DOI

Coppo R. Proteasome inhibitors in progressive renal diseases. Nephrol. Dial Transpl. 2014;29:i25–i30. doi: 10.1093/ndt/gft271. PubMed DOI

Xin G., Shi W., Xu L.X., Su Y., Yan L.J., Li K.S. Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J. Nephrol. 2013;26:683–690. doi: 10.5301/jn.5000218. PubMed DOI

Kim M.J., McDaid J.P., McAdoo S.P., Barratt J., Molyneux K., Masuda E.S., Pusey C.D., Tam F.W. Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients. J. Immunol. 2012;189:3751–3758. doi: 10.4049/jimmunol.1102603. PubMed DOI

McAdoo S., Tam F.W.K. Role of the Spleen Tyrosine Kinase Pathway in Driving Inflammation in IgA Nephropathy. Semin. Nephrol. 2018;38:496–503. doi: 10.1016/j.semnephrol.2018.05.019. PubMed DOI PMC

Liu X.W., Li D.M., Xu G.S., Sun S.R. Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin a nephropathy manifesting with nephrotic syndrome. Int. J. Clin. Pharmacol. Ther. 2010;48:509–513. doi: 10.5414/CPP48509. PubMed DOI

Cheng G., Liu D., Margetts P., Liu L., Zhao Z., Liu Z., Tang L., Fang Y., Li H., Guo Y., et al. Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy. Nephrology. 2015;20:77–84. doi: 10.1111/nep.12359. PubMed DOI

Samy E., Wax S., Huard B., Hess H., Schneider P. Targeting BAFF and APRIL in systemic lupus erythematosus and oTher. antibody-associated diseases. Int. Rev. Immunol. 2017;36:3–19. doi: 10.1080/08830185.2016.1276903. PubMed DOI

Zhai Y., Zhu L., Shi S., Liu L., Lv J., Zhang H. Increased APRIL expression induces IgA1 aberrant glycosylation in IgA nephropathy. Medicine. 2016;95:e3099. doi: 10.1097/MD.0000000000003099. PubMed DOI PMC

Isenberg D., Gordon C., Licu D., Copt S., Rossi C.P., Wofsy D. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE):52-week data (APRIL-SLE randomised trial) Ann. Rheum. Dis. 2015;74:2006–2015. doi: 10.1136/annrheumdis-2013-205067. PubMed DOI PMC

Lenert A., Niewold T.B., Lenert P. Spotlight on blisibimod and its potential in the treatment of systemic lupus erythematosus:evidenc to date. Drug Des. Devel Ther. 2017;11:747–757. doi: 10.2147/DDDT.S114552. PubMed DOI PMC

Richardson P.G., Barlogie B., Berenson J., Singhal S., Jagannath S., Irwin D., Rajkumar S.V., Srkalovic G., Alsina M., Alexanian R., et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med. 2003;26:2609–2617. doi: 10.1056/NEJMoa030288. PubMed DOI

Coppo R., Camilla R., Alfarano A., Balegno S., Mancuso D., Peruzzi L., Amore A., Canton A.D., Sepe V., Tovo P., et al. Upregulation of the immunoproteasome in peripheral blood mononuclear cells of patients with IgA nephropathy. Kidney Int. 2009;75:536–541. doi: 10.1038/ki.2008.579. PubMed DOI

Bahleda R., Le Deley M., Bernard A., Chaturvedi S., Hanley M., Poterie A., Gazzah A., Varga A., Touat M., Deutsch E., et al. Phase I trial of bortezomib daily dose: Safety, pharmacokinetic profile, biological effects and early clinical evaluation in patients with advanced solid tumors. Investig. New Drugs. 2017;5:66. PubMed

Ma T.K., McAdoo S.P., Tam F.W.K. Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: From bench to bedside and beyond. Nephrol. Dial Transpl. 2017;32:i138. doi: 10.1093/ndt/gfw336. PubMed DOI PMC

McAdoo S.P., Bhangal G., Page T., Cook H.T., Pusey C.D., Tam F.W.K. Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression. Kidney Int. 2015;88:52–60. doi: 10.1038/ki.2015.29. PubMed DOI PMC

Taylor P.C., Genovese M.C., Greenwood M., Ho M., Nasonov E., Oemar B., Stoilov R., Vencovsky J., Weinblatt M. OSKIRA-4: A phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy. Ann. Rheum. Dis. 2015;74:2123–2129. doi: 10.1136/annrheumdis-2014-205361. PubMed DOI

Simonson M.S., Wann S., Mene P., Dubyak G.R., Kester M., Nakazato Y., Sedor J.R., Dunn M.J. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-Fos expression, and mitogenesis in rat mesangial cells. J. Clin. Investig. 1989;83:708–712. doi: 10.1172/JCI113935. PubMed DOI PMC

Ohta K., Hirata Y., Shichiri M., Kanno K., Emori T., Tomita K., Marumo F. Urinary excretion of endothelin-1 in normal subjects and patients with renal disease. Kidney Int. 1991;39:307–311. doi: 10.1038/ki.1991.38. PubMed DOI

Lehrke I., Waldherr R., Ritz E., Wagner J. Renal endothelin-1 and endothelin receptor type B expression in glomerular diseases with proteinuria. J. Am. Soc. Nephrol. 2001;12:2321–2329. PubMed

Maixnerova D., Merta M., Reiterova J., Stekrova J., Rysava R., Obeidova H., Viklicky O., Potmesil P., Tesar V. The influence of three endothelin-1 polymorphisms on the progression of IgA nephropathy. Folia Biol. 2007;53:27–32. PubMed

Tycova I., Hruba P., Maixnerova D., Girmanova E., Mrazova P., Straňavova L., Zachoval R., Merta M., Slatinska J., Kollar M., et al. Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis. Physiol. Res. 2018;67:93–105. doi: 10.33549/physiolres.933670. PubMed DOI

Nakamura T., Ebihara I., Fukui M., Tomino Y., Koide H. Effect of a specific endothelin receptor a antagonist on glomerulonephritis of ddY mice with IgA nephropathy. Nephron. 1996;72:454–460. doi: 10.1159/000188912. PubMed DOI

Trachtman H., Nelson P., Adler S., Campbell K.N., Chaudhuri A., Derebail V.K., Gambaro G., Gesualdo L., Gipson D.S., Hogan J., et al. DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS. J. Am. Soc. Nephrol. 2018;29:2745–2754. doi: 10.1681/ASN.2018010091. PubMed DOI PMC

Komers R., Diva U., Inrig J.K., Loewen A., Trachtman H., Rote W.E. Study design of the phase 3 sparsentan versus irbesartan (DUPLEX) study in patients with focal segmental glomerulosclerosis. Kidney Int. Rep. 2020;5:494–502. doi: 10.1016/j.ekir.2019.12.017. PubMed DOI PMC

Shelton L.M., Park B.K., Copple I.M. Role of Nrf2 in protection against acute Kidney injury. Kidney Int. 2013;84:1090–1095. doi: 10.1038/ki.2013.248. PubMed DOI

Pergola P.E., Raskin P., Toto R.D., Meyer C.J., Huff J.W., Grossman E.B., Krauth M., Ruiz S., Audhya P., Christ-Schmidt H., et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N. Engl. J. Med. 2011;365:327–336. doi: 10.1056/NEJMoa1105351. PubMed DOI

Block G.A. Primary Efficacy Analyses from a Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients with IgA Nephropathy. ASN Kidney Week. 2018 doi: 10.1093/ndt/gfy104.FP110. poster TH-PO1039. DOI

Rossing P., Block G.A., Chin M.P., Goldsberry A., Heerspink H.J.L., McCullough P.A., Meyer C.J., Packham D., Pergola P.E., Spinowitz B., et al. Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease. Kidney Int. 2019;96:1030–1036. doi: 10.1016/j.kint.2019.04.027. PubMed DOI

Evaluation of the cytochrome P450 2C19 and 3A4 inhibition potential of the complement factor 5a receptor 1 antagonist ACT-1014-6470 in vitro and in vivo

New Treatment Strategies for IgA Nephropathy: Targeting Plasma Cells as the Main Source of Pathogenic Antibodies

Outcome of 313 Czech Patients With IgA Nephropathy After Renal Transplantation