Abstract
Immunoglobulin A nephropathy (IgAN) is the most frequently occurring primary glomerulonephritis in Caucasian and Asian populations. Nonetheless, therapeutic recommendations are based on weak evidence, large controlled trials are scarce and, in particular, the additional value of immunosuppression beyond comprehensive supportive measures is not well-established. The use of immunosuppressants is supported by experimental insights into IgAN pathogenesis that suggest an autoimmune component in disease development. The so-called “multi-hit” theory comprises multiple steps, starting with defective glycosylation of IgA subclass IgA1 that results in overproduction of galactose-deficient IgA1 (Gd-IgA1), occurrence of anti-Gd-IgA1 autoantibodies, and mesangial deposition of nephritogenic immune complexes. This eventually results in an increased mesangial cell proliferation, inflammatory responses, and complement activation. Recent genome-wide association studies have identified several susceptibility genes, many of which support the “multi-hit” concept. In light of these discoveries, it is astonishing that the vast majority of adult IgAN patients obviously do not need and/or benefit from immunosuppressive therapies in the first place. In fact, a number of supportive measures are highly effective in reducing the risk for disease progression in many patients. These measures need to be optimized before immunosuppression should be considered at all. In this review we focus on the underlying pathogenetic cornerstones and the central question of whether systemic inflammation in adult IgAN patients should be treated. Treatment options in children with IgAN are also discussed.
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References
Wyatt RJ, Julian BA (2013) IgA nephropathy. N Engl J Med 368:2402–2414
Floege J, Eitner F (2011) Current therapy for IgA nephropathy. J Am Soc Nephrol 22:1785–1794
Schena FP (1990) A retrospective analysis of the natural history of primary IgA nephropathy worldwide. Am J Med 89:209–215
Berger J, Hinglais N (1968) Intercapillary deposits of IgA-IgG. J Urol Nephrol (Paris) 74:694–695
McGrogan A, Franssen CF, de Vries CS (2011) The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 26:414–430
Berthoux F (1990) Annual incidence of glomerulonephritis in the extended Rhone-Alpes region in 1987–1988. Presse Med 19:1417
Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, Schena FP, Italian Immunopathology Group, Italian Society of Nephrology (2004) The Italian experience of the national registry of renal biopsies. Kidney Int 66:890–894
Hanko JB, Mullan RN, O’Rourke DM, McNamee PT, Maxwell AP, Courtney AE (2009) The changing pattern of adult primary glomerular disease. Nephrol Dial Transplant 24:3050–3054
Zhou FD, Zhao MH, Zou WZ, Liu G, Wang H (2009) The changing spectrum of primary glomerular diseases within 15 years: a survey of 3331 patients in a single Chinese centre. Nephrol Dial Transplant 24:870–876
Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, Tsuruya K, Kiyomoto H, Iida H, Sasaki T, Higuchi M, Hattori M, Oka K, Kagami S, Nagata M, Kawamura T, Honda M, Fukasawa Y, Fukatsu A, Morozumi K, Yoshikawa N, Yuzawa Y, Matsuo S, Kiyohara Y, Joh K, Taguchi T, Makino H, Committee for Standardization of Renal Pathological Diagnosis and Working Group for Renal Biopsy Database (2011) Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan. Clin Exp Nephrol 15:493–503
Magistroni R, D’Agati VD, Appel GB, Kiryluk K (2015) New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney Int 88:974–989
Levy M (1989) Familial cases of Berger’s disease and anaphylactoid purpura: more frequent than previously thought. Am J Med 87:246–248
Julian BA, Quiggins PA, Thompson JS, Woodford SY, Gleason K, Wyatt RJ (1985) Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N Engl J Med 312:202–208
Scolari F, Amoroso A, Savoldi S, Mazzola G, Prati E, Valzorio B, Viola BF, Nicola B, Movilli E, Sandrini M, Campanini M, Maiorca R (1999) Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis 33:857–865
Karnib HH, Sanna-Cherchi S, Zalloua PA, Medawar W, D’Agati VD, Lifton RP, Badr K, Gharavi AG (2007) Characterization of a large Lebanese family segregating IgA nephropathy. Nephrol Dial Transplant 22:772–777
Tsuboi N, Kawamura T, Okonogi H, Ishii T, Utsunomiya Y, Hosoya T (2011) Discordant clinicopathological features in monozygotic twins with IgA nephropathy. Nephrol Dial Transplant 26:4146–4148
Schena FP, Scivittaro V, Ranieri E, Sinico R, Benuzzi S, Di Cillo M, Aventaggiato L (1993) Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy. Clin Exp Immunol 92:139–144
Feehally J, Farrall M, Boland A, Gale DP, Gut I, Heath S, Kumar A, Peden JF, Maxwell PH, Morris DL, Padmanabhan S, Vyse TJ, Zawadzka A, Rees AJ, Lathrop M, Ratcliffe P (2015) HLA has strongest association with IgA nephropathy in genome-wide analysis. J Am Soc Nephrol 21:1791–1797
Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP (2011) Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 43:321–327
Yu XQ, Li M, Zhang H, Low HQ, Wei X, Wang JQ, Sun LD, Sim KS, Li Y, Foo JN, Wang W, Li ZJ, Yin XY, Tang XQ, Fan L, Chen J, Li RS, Wan JX, Liu ZS, Lou TQ, Zhu L, Huang XJ, Zhang XJ, Liu ZH, Liu JJ (2011) A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet 44:178–182
Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, Fasel D, Lata S, Prakash S, Shapiro S, Fischman C, Snyder HJ, Appel G, Izzi C, Viola BF, Dallera N, Del Vecchio L, Barlassina C, Salvi E, Bertinetto FE, Amoroso A, Savoldi, Rocchietti M, Amore A, Peruzzi L, Coppo R, Salvadori M, Ravani P, Magistroni R, Ghiggeri GM, Caridi G, Bodria M, Lugani F, Allegri L, Delsante M, Maiorana M, Magnano A, Frasca G, Boer E, Boscutti G, Ponticelli C, Mignani R, Marcantoni C, Di Landro D, Santoro D, Pani A, Polci R, Feriozzi S, Chicca S, Galliani M, Gigante M, Gesualdo L, Zamboli P, Battaglia GG, Garozzo M, Maixnerová D, Tesar V, Eitner F, Rauen T, Floege J, Kovacs T, Nagy J, Mucha K, Pączek L, Zaniew M, Mizerska-Wasiak M, Roszkowska-Blaim M, Pawlaczyk K, Gale D, Barratt J, Thibaudin L, Berthoux F, Canaud G, Boland A, Metzger M, Panzer U, Suzuki H, Goto S, Narita I, Caliskan Y, Xie J, Hou P, Chen N, Zhang H, Wyatt RJ, Novak J, Julian BA, Feehally J, Stengel B, Cusi D, Lifton RP, Gharavi AG (2014) Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46:1187–1196
Ambruzs JM, Walker PD, Larsen CP (2014) The histopathologic spectrum of kidney biopsies in patients with inflammatory bowel disease. Clin J Am Soc Nephrol 9:265–270
Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, Snyder HJ, Choi M, Hou P, Scolari F, Izzi C, Gigante M, Gesualdo L, Savoldi S, Amoroso A, Cusi D, Zamboli P, Julian BA, Novak J, Wyatt RJ, Mucha K, Perola M, Kristiansson K, Viktorin A, Magnusson PK, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Boland A, Metzger M, Thibaudin L, Wanner C, Jager KJ, Goto S, Maixnerova D, Karnib HH, Nagy J, Panzer U, Xie J, Chen N, Tesar V, Narita I, Berthoux F, Floege J, Stengel B, Zhang H, Lifton RP, Gharavi AG (2012) Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet 8:e1002765
Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA (2011) The pathophysiology of IgA nephropathy. J Am Soc Nephrol 22:17951–803
Conley ME, Cooper MD, Michael AF (1980) Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest 66:1432143–6
Scinicariello F, Attanasio R (2001) Intraspecies heterogeneity of immunoglobulin alpha-chain constant region genes in rhesus macaques. Immunology 103:441–448
Allen AC, Bailey EM, Brenchley PE, Buck KS, Barratt J, Feehally J (2001) Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: observations in three patients. Kidney Int 60:969–973
Novak J, Julian BA, Tomana M, Mestecky J (2008) IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy. Semin Nephrol 28:78–87
Zhao N, Hou P, Lv J, Moldoveanu Z, Li Y, Kiryluk K, Gharavi AG, Novak J, Zhang H (2012) The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. Kidney Int 82:790–796
Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J (1999) Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest 104:73–81
Suzuki H, Moldoveanu Z, Hall S, Brown R, Vu HL, Novak L, Julian BA, Tomana M, Wyatt RJ, Edberg JC, Alarcón GS, Kimberly RP, Tomino Y, Mestecky J, Novak J (2008) IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest 118:629–639
Stuchlova Horynova M, Vrablikova A, Stewart TJ, Takahashi K, Czernekova L, Yamada K, Suzuki H, Julian BA, Renfrow MB, Novak J, Raska M (2015) N-acetylgalactosaminide alpha2,6-sialyltransferase II is a candidate enzyme for sialylation of galactose-deficient IgA1, the key autoantigen in IgA nephropathy. Nephrol Dial Transplant 30:234–238
Suzuki H, Fan R, Zhang Z, Brown R, Hall S, Julian BA, Chatham WW, Suzuki Y, Wyatt RJ, Moldoveanu Z, Lee JY, Robinson J, Tomana M, Tomino Y, Mestecky J, Novak J (2009) Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119:1668–1677
Mestecky J, Tomana M, Moldoveanu Z, Julian BA, Suzuki H, Matousovic K, Renfrow MB, Novak L, Wyatt RJ, Novak J (2008) Role of aberrant glycosylation of IgA1 molecules in the pathogenesis of IgA nephropathy. Kidney Blood Press Res 31:29–37
Berthoux F, Suzuki H, Thibaudin L, Yanagawa H, Maillard N, Mariat C, Tomino Y, Julian BA, Novak J (2012) Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy. J Am Soc Nephrol 23:1579–1587
Lai KN, Tang SC, Guh JY, Chuang TD, Lam MF, Chan LY, Tsang AW, Leung JC (2003) Polymeric IgA1 from patients with IgA nephropathy upregulates transforming growth factor-beta synthesis and signal transduction in human mesangial cells via the renin- angiotensin system. J Am Soc Nephrol 14:3127–3137
Moura IC, Centelles MN, Arcos-Fajardo M, Malheiros DM, Collawn JF, Cooper MD, Monteiro RC (2001) Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J Exp Med 194:417–425
Launay P, Grossetête B, Arcos-Fajardo M, Gaudin E, Torres SP, Beaudoin L, Patey-Mariaud de Serre N, Lehuen A, Monteiro RC (2000) Fcalpha receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger’s disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice. J Exp Med 191:1999–2009
Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, Myers BD (2002) Podocytopenia and disease severity in IgA nephropathy. Kidney Int 61:1475–1485
Lai KN, Leung JC, Chan LY, Saleem MA, Mathieson PW, Tam KY, Xiao J, Lai FM, Tang SC (2009) Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol Dial Transplant 24:62–72
Daha MR, van Kooten C (2016) Role of complement in IgA nephropathy. J Neprol 29:1–4
Haas M (2005) Histology and immunohistology of IgA nephropathy. J Nephrol 18:676–680
Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ, Stahl GL, Matsushita M, Fujita T, van Kooten C, Daha MR (2006) Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol 17:1724–1734
Roos A, Bouwman LH, van Gijlswijk-Janssen DJ, Faber-Krol MC, Stahl GL, Daha MR (2001) Human IgA activates the complement system via the mannan-binding lectin pathway. J Immunol 167:2861–2868
Zhu L, Zhai YL, Wang FM, Hou P, Lv JC, Xu DM, Shi SF, Liu LJ, Yu F, Zhao MH, Novak J, Gharavi AG, Zhang H (2015) Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy. J Am Soc Nephrol 26:195–204
Kidney Disease/Improving Global Outcomes (2012) KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2(2). http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf
Cheng J, Zhang W, Zhang XH, He Q, Tao XJ, Chen JH (2009) ACEI/ARB therapy for IgA nephropathy: a meta analysis of randomised controlled trials. Int J Clin Pract 63:880–888
Floege J, Feehally J (2013) Treatment of IgA nephropathy and Henoch–Schonlein nephritis. Nat Rev Nephrol 9:320–327
Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Möller K, Wigger M, Peruzzi L, Mehls O, Schaefer F, Trial Group ESCAPE (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650
Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J, STOP–IgAN Investigators (2015) Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med 373:2225–2236
Manno C, Torres DD, Rossini M, Pesce F, Schena FP (2010) Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant 24:3694–3701
Ruggenenti P, Perticucci E, Cravedi P, Gambara V, Costantini M, Sharma SK, Perna A, Remuzzi G (2008) Role of remission clinics in the longitudinal treatment of CKD. J Am Soc Nephrol 19:1213–1224
J L, D X, Perkovic V, Ma X, Johnson DW, Woodward M, Levin A, Zhang H, Wang H, TESTING Study Group (2012) Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol 23:1108–1116
Vecchio M, Bonerba B, Palmer SC, Craig JC, Ruospo M, Samuels JA, Molony DA, Schena FP, Strippoli GF (2015) Immunosuppressive agents for treating IgA nephropathy. Cochrane Database Syst Rev 3:CD003965
Kawamura T, Yoshimura M, Miyazaki Y, Okamoto H, Kimura K, Hirano K, Matsushima M, Utsunomiya Y, Ogura M, Yokoo T, Okonogi H, Ishii T, Hamaguchi A, Ueda H, Furusu A, Horikoshi S, Suzuki Y, Shibata T, Yasuda T, Shirai S, Imasawa T, Kanozawa K, Wada A, Yamaji I, Miura N, Imai H, Kasai K, Soma J, Fujimoto S, Matsuo S, Tomino Y, Group SIANS (2014) A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol Dial Transplant 29:1546–1553
Feehally J, Coppo R, Troyanov S, Bellur SS, Cattran D, Cook T, Roberts IS, Verhave JC, Camilla R, Vergano L, Egido J, Wiecek A, Karkoszka H, Tesar V, Maixnerova D, Ots-Rosenberg M, Quaglia M, Rollino C, Magistroni R, Cusinato S, Cravero R, Peruzzi L, Lundberg S, Gesualdo L, Cancarini G, Feriozzi S, Ferrario F, VALIGA study of ERA-EDTA Immunonephrology Working G roup (2016) Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron 132:15–24
Tesar V, Troyanov S, Bellur S, Verhave JC, Cook HT, Feehally J, Roberts IS, Cattran D, Coppo R, VALIGA study of the ERA-EDTA Immunonephrology Working Group (2015) Corticosteroids in IgA nephropathy: a retrospective analysis from the VALIGA study. J Am Soc Nephrol 26:2248–2258
Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, Locatelli F (1999) Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353:883–887
Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, Ponticelli C, Locatelli F (2004) Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 15:157–163
Sarcina C, Tinelli C, Ferrario F, Visciano B, Pani A, De Silvestri A, De Simone I, Del Vecchio L, Terraneo V, Furiani S, Santagostino G, Corghi E, Pozzi C (2016) Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy. PLoS One 11:e0158584
Ballardie FW, Roberts IS (2002) Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 13:142–148
Pozzi C, Andrulli S, Pani A, Scaini P, Del Vecchio L, Fogazzi G, Vogt B, De Cristofaro V, Allegri L, Cirami L, Procaccini AD, Locatelli F (2010) Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J Am Soc Nephrol 2110:1783–1790
Sarcina C, Tinelli C, Ferrario F, Pani A, De Silvestri A, Scaini P, Del Vecchio L, Alberghini E, Buzzi L, Baragetti I, Pozzi C (2016) 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 11:973–981
Lv J, Yang Y, Zhang H, Chen W, Pan X, Guo Z, Wang C, Li S, Zhang J, Zhang J, Liu L, Shi S, Wang S, Chen M, Cui Z, Chen N, Yu X, Zhao M, Wang H (2013) Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study. J Am Soc Nephrol 24:2118–2125
Chen X, Chen P, Cai G, Wu J, Cui Y, Zhang Y, Liu S, Tang L (2002) A randomized control trial of mycophenolate mofeil treatment in severe IgA nephropathy. Zhonghua Yi Xue Za Zhi 82:796–801
Tang S, Leung JC, Chan LY, Lui YH, Tang CS, Kan CH, Ho YW, Lai KN (2005) Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int 68:802–812
Tang SC, Tang AW, Wong SS, Leung JC, Ho YW, Lai KN (2010) Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int 77:543–549
Liu X, Dewei D, Sun S, Xu G, Liu H, He L, Zhang P (2014) Treatment of severe IgA nephropathy: mycophenolate mofetil/prednisone compared to cyclophosphamide/prednisone. Int J Clin Pharmacol Ther 52:95–102
Maes BD, Oyen R, Claes K, Evenepoel P, Kuypers D, Vanwalleghem J, Van Damme B, Vanrenterghem YF (2004) Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int 65:1842–1849
Frisch G, Lin J, Rosenstock J, Markowitz G, D’Agati V, Radhakrishnan J, Preddie D, Crew J, Valeri A, Appel G (2005) Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 20:2139–2145
Hogg RJ, Bay RC, Jennette JC, Sibley R, Kumar S, Fervenza FC, Appel G, Cattran D, Fischer D, Hurley RM, Cerda J, Carter B, Jung B, Hernandez G, Gipson D, Wyatt RJ (2015) Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy. Am J Kidney Dis 66:783–791
Lv J, Zhang H, Cui Z, Su T, Zhang Y, Wang H (2008) Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy. Nephrol Dial Transplant 23:2868–2872
Lafayette RA, Canetta PA, Rovin BH, Appel GB, Novak J, Nath KA, Sethi S, Tumlin JA, Mehta K, Hogan M, Erickson S, Julian BA, Leung N, Enders FT, Brown R, Knoppova B, Hall S, Fervenza FC (2016) A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol. doi:10.1681/ASN.2016060640
Peng W, Tang Y, Jiang Z, Li Z, Mi X, Qin W (2016) The effect of calcineurin inhibitors in the treatment of IgA nephropathy: A systematic review and meta-analysis (PRISMA). Medicine 95:e4731
Masutani K, Tsuchimoto A, Yamada T, Hirakawa M, Mitsuiki K, Katafuchi R, Hirakata H, Kitazono T, Tsuruya K, West Japan Study Group for Therapy of IgA Nephropathy Investigators (2016) Comparison of steroid-pulse therapy and combined with mizoribine in IgA nephropathy: a randomized controlled trial. Clin Exp Nephrol 20:896–903
Kuppe C, van Roeyen C, Leuchtle K, Kabgani N, Vogt M, Van Zandvoort M, Smeets B, Floege J, Gröne H, Moeller MJ (2016) Investigations of glucocorticoid action in GN. J Am Soc Nephrol. doi:10.1681/ASN.2016010060
Ma TK, McAdoo SP, Tam FW (2016) Spleen tyrosine kinase: a crucial player and potential therapeutic target in renal disease. Nephron 133:261-9
Isenberg D, Gordon C, Licu D, Copt S, Rossi CP, Wofsy D (2006) 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 74:2006–2015
Ginzler EM, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer NG (2012) Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 14:R33
Rojas-Rivera J, Fernandez-Juarez G, Praga M (2015) Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease? Clin Kidney J 8:477–481
Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator SN, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo AB, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H, Working Group of the International IgA Nephropathy Network and the Renal Pathology Society (2010) The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 77:921–927
Ikezumi Y1, Suzuki T, Imai N, Ueno M, Narita I, Kawachi H, Shimizu F, Nikolic-Paterson DJ, Uchiyama M (2006) Histological differences in new-onset IgA nephropathy between children and adults. Nephrol Dial Transplant 21:3466–3474
D’Amico G (2004) Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 24:179–196
Nozawa R, Suzuki J, Takahashi A, Isome M, Kawasaki Y, Suzuki S, Suzuki H (2005) Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation. Clin Nephrol 64:171–179
Coppo R (2008) Pediatric IgA nephropathy: clinical and therapeutic perspectives. Semin Nephrol 28:18–26
Kamei K, Harada R, Hamada R, Sakai T, Hamasaki Y, Hataya H, Ito S, Ishikura K, Honda M (2016) Proteinuria during follow-up period and long-term renal survival of childhood IgA nephropathy. PLoS One 11:e0150885
Yoshikawa N, Ito H, Sakai T, Takekoshi Y, Honda M, Awazu M, Ito K, Iitaka K, Koitabashi Y, Yamaoka K, Nakagawa K, Nakamura H, Matsuyama S, Seino Y, Takeda N, Hattori S, Ninomiya M, The Japanese Pediatric IgA Nephropathy Treatment Study Group (1999) A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. J Am Soc Nephrol 10:101–109
Kamei K, Nakanishi K, Ito S, Saito M, Sako M, Ishikura K, Hataya H, Honda M, Iijima K, Yoshikawa N, Japanese Pediatric IgA Nephropathy Treatment Study Group (2011) Long-term results of a randomized controlled trial in childhood IgA nephropathy. Clin J Am Soc Nephrol 6:1301–1307
Yoshikawa N, Honda M, Iijima K, Awazu M, Hattori S, Nakanishi K, Ito H, Japanese Pediatric IgA Nephropathy Treatment Study Group (2006) Steroid treatment for severe childhood IgA nephropathy: a randomized, controlled trial. Clin J Am Soc Nephrol 1:511–517
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J. Floege has received consultancy honoraria from Pharmalink, Sweden. T. Rauen has no conflicts of interest to declare.
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Rauen, T., Floege, J. Inflammation in IgA nephropathy. Pediatr Nephrol 32, 2215–2224 (2017). https://doi.org/10.1007/s00467-017-3628-1
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DOI: https://doi.org/10.1007/s00467-017-3628-1