Advertisement

Clinical and histological features and therapeutic strategies for IgA nephropathy

  • Takahito MoriyamaEmail author
Invited review article
  • 97 Downloads

Abstract

Chronic glomerulonephritis is the second most common reason, after diabetic nephropathy, for initiation of dialysis in Japan and IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis. In the half century since IgAN was initially reported, our understanding of the long-term prognosis, clinical and histological features, pathogenesis of onset and progression, risk factors for progression, and appropriate treatment under different clinical and histological conditions, has steadily increased. Strong experimental and clinical evidence, the Clinical Practice Guidelines for IgA Nephropathy in Japan, the Oxford Classification, and the Kidney Disease Improving Global Outcomes guidelines have all contributed to the appropriate treatment of IgAN. Several intensive therapies, such as tonsillectomy, steroid therapy, and their combinations, can result in clinical remission, and prevent the progression to end stage renal disease (ESRD). However, some IgAN patients still progress to ESRD even when treated with intensive therapies. In this review, we discuss the clinical and histological features of IgAN, focusing primarily on our previous reports, and our opinions on therapeutic strategies for IgAN.

Keywords

IgA nephropathy Prognosis Risk factors Guidelines Treatments 

Notes

Acknowledgements

I am grateful to the Japanese Society of Nephrology for this clinical scientific award. I would like to thank Dr. Kazuho Honda, Dr. Kosaku Nitta and Dr. Hiroshi Nihei for special mentorship and Dr. Noriko Mori (Shizuoka general hospital) for giving me strong motivation to treat and study IgA nephropathy. I thank Richard Robins, PhD, and Cathel Kerr, BSc, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Compliance with ethical standards

Conflicts of interest

The author declares there is no conflict of interest.

References

  1. 1.
    Berger J, Hinglais N. Les dépôts intercapillaries d’IgA-IgG. J Urol Nephrol. 1968;74:694–5.Google Scholar
  2. 2.
    D’Amico G. Clinical features and natural history in adults with IgA nephropathy. Am J Kidney Dis. 1988;12:353–7.CrossRefGoogle Scholar
  3. 3.
    Alamartine E, Sabatier JC, Guerin C, Berliet JM, Berthoux F. Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analysis. Am J Kidney Dis. 1991;18:12–9.CrossRefGoogle Scholar
  4. 4.
    Koyama A, Igarashi M, Kobayashi M. Coworkers of the research group on progressive renal disease: natural history and risk factors for immunoglobulin A nephropathy in Japan. Am J Kidney Dis. 1997;29:526–32.CrossRefGoogle Scholar
  5. 5.
    Sakai H, Abe K, Kobayashi Y, Koyama A, Shigematsu H, Harada T, Yoshikawa N, Arakawa M, Itoh H, Osawa K, Sakai O, Dohi K, Yamanaka N, Nagasawa T, Kurokawa K. Clinical guidelines of IgA nephropathy. Jpn J Nephrol. 1995;37:417–21.Google Scholar
  6. 6.
    Tomino Y, Sakai H. Special study group (IgA nephropathy) on progressive glomerular disease clinical guidelines for immunoglobulin A(IgA) nephropathy in Japan, second version. Clin Exp Nephrol. 2003;7:93–7.CrossRefGoogle Scholar
  7. 7.
    Matsuo S, Kawamura T, Joh K, Utsunomiya Y, Okonogi H, Miyazaki Y, Koike K, Yokoo T, Matsushima M, Komura H, Ogura M, Horikoshi T, Suzuki Y, Furusu A, Kimura K, Yasuda T, Shirai S, Endo M, Hattori M, Akioka Y, Hirano K, Katafuchi R, Hisano S, Shimizu A, Hashiguchi A, Furukawa T, Tomino Y. Clinical guidelines for immunoglobulin A (IgA) nephropathy in Japan third version. Nippon Jinzo Gakkai Shi. 2001;53:123–35.Google Scholar
  8. 8.
    Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, Kitamura H, Goto M, Yasuda T, Sato M, Urushihara M, Kondo S, Kagami S, Yasuda Y, Komatsu H, Takahara M, Haraguchi Y, Kimura K, Matsuo S. Evidence-based clinical practice guidelines for IgA nephropathy 2014. Clin Exp Nephrol. 2016;20:511–35.CrossRefGoogle Scholar
  9. 9.
    A 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;76:534–45.CrossRefGoogle Scholar
  10. 10.
    A Working Group of the International IgA Nephropathy Network and the Renal Pathology Society. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56.CrossRefGoogle Scholar
  11. 11.
    Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J, IgAN Classification Working Group of the International IgA Nephropathy Network and the Renal Pathology Society; Conference Participants. Oxford classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91:1014–21.CrossRefGoogle Scholar
  12. 12.
    Kobayashi Y, Fujii K, Hiki Y, Tateno S. Steroid therapy in IgA nephropathy: prospective pilot study in moderate proteinuric cases. Q J Med. 1986;61:935–43.Google Scholar
  13. 13.
    Kobayashi Y, Hiki Y, Kokubo T, Horii A, Tateno S. Steroid therapy during the early stage of progressive IgA nephropaty. Nephron. 1996;72:237–42.CrossRefGoogle Scholar
  14. 14.
    Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, Locatelli F. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 1999;13(353):883–7.CrossRefGoogle Scholar
  15. 15.
    Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, Ponticelli C, Locatelli F. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. Am J Soc Nephrol. 2004;15:157–63.CrossRefGoogle Scholar
  16. 16.
    Hotta O, Miyazaki M, Furuta T, Tomioka S, Chiba S, Horigome I, Abe K, Taguma Y. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis. 2001;38:736–43.CrossRefGoogle Scholar
  17. 17.
    Miura N, Imai H, Kikuchi S, Hayashi S, Endoh M, Kawamura T, Tomino Y, Moriwaki K, Kiyomoto H, Kohagura K, Nakazawa E, Kusano E, Mochizuki T, Nomura S, Sasaki T, Kashihara N, Soma J, Tomo T, Nakabayashi I, Yoshida M, Watanabe T. Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy. Clin Exp Nephrol. 2009;13:460–6.CrossRefGoogle Scholar
  18. 18.
    Matsuzaki K, Suzuki Y, Nakata J, Sakamoto N, Horikoshi S, Kawamura T, Matsuo S, Tomino Y. Nationwide survey on current treatments for IgA nephropathy in Japan. Clin Exp Nephrol. 2013;17:827–33.CrossRefGoogle Scholar
  19. 19.
    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, Special IgA Nephropathy Study Group. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol Dial Transpl. 2014;29:1546–53.CrossRefGoogle Scholar
  20. 20.
    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 1,012 patients at a single center in Japan. PLoS One. 2014;9:e91756.CrossRefGoogle Scholar
  21. 21.
    Lee H, Kim DK, Oh KH, Joo KW, Kim YS, Chae DW, Kim S, Chin HJ. Mortality of IgA nephropathy patients: a single center experience over 30 years. PLoS ONE. 2012;7:e51225.CrossRefGoogle Scholar
  22. 22.
    Komatsu H, Fujimoto S, Hara S, Fukuda A, Fukudome K, Yamada K, Sato Y, Kitamura K. Recent therapeutic strategies improve renal outcome in patients with IgA nephropathy. Am J Nephrol. 2009;30:19–25.CrossRefGoogle Scholar
  23. 23.
    Okonogi H, Kawamura T, Joh K, Koike K, Miyazaki Y, Ogura M, Tsuboi N, Hirano K, Matsushima M, Yokoo T, Horikoshi S, Suzuki Y, Yasuda T, Shirai S, Shibata T, Hattori M, Akioka Y, Katafuchi R, Hashiguchi A, Hisano S, Shimizu A, Kimura K, Maruyama S, Matsuo S, Tomino Y, Special IgA Nephropathy Study Group. A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity. Clin Exp Nephrol. 2018.  https://doi.org/10.1007/s10157-018-1657-0 [Epub ahead of print].Google Scholar
  24. 24.
    Wakai K, Kawamura T, Endoh M, Kojima M, Tomino Y, Tamakoshi A, Ohno Y, Inaba Y, Sakai H. A scoring system to predict renal outcome in IgA nephropathy: from a nationwide prospective study. Nephrol Dial Transplant. 2006;21:2800–8.CrossRefGoogle Scholar
  25. 25.
    Goto M, Wakai K, Kawamura T, Ando M, Endoh M, Tomino Y. A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10 year prospective cohort study. Nephrol Dial Transplant. 2009;24:3068–74.CrossRefGoogle Scholar
  26. 26.
    Bjørneklett R, Vikse BE, Bostad L, Leivestad T, Iversen BM. Long-term risk of ESRD in IgAN; validation of Japanese prognostic model in a Norwegian cohort. Nephrol Dial Transpl. 2012;27:1485–91.CrossRefGoogle Scholar
  27. 27.
    Moriyama T, Honda K, Nitta K, Yumura W, Nihei H. The effectiveness of steroid therapy for patients with advanced IgA nephropathy and deteriorated renal function. Clin Exp Nephrol. 2004;8:237–42.CrossRefGoogle Scholar
  28. 28.
    Moriyama T, Amamiya N, Ochi A, Tsuruta Y, Shimizu A, Kojima C, Itabashi M, Takei T, Uchida K, Nitta K. Long-term beneficial effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for patients with advanced immunoglobulin A nephropathy and impaired renal function. Clin Exp Nephrol. 2011;15:700–7.CrossRefGoogle Scholar
  29. 29.
    Moriyama T, Amemiya N, Ochi A, Tsuruta Y, Shimizu A, Itabashi M, Takei T, Uchida K, Nitta K. Comparison of steroids and angiotensin receptor blockers for patients with advanced IgA nephropathy and impaired renal function. Am J Nephrol. 2011;34:233–40.CrossRefGoogle Scholar
  30. 30.
    Moriyama T, Nakayama K, Ochi A, Amemiya N, Tsuruta Y, Kojima C, Itabashi M, Takei T, Uchida K, Nitta K. Comparison of inhibitors of renin-angiotensin-aldosterone system (RAS) and combination therapy of steroids plus RAS inhibitors for patients with advanced immunoglobulin A nephropathy and impaired renal function. Clin Exp Nephrol. 2012;16:231–7.CrossRefGoogle Scholar
  31. 31.
    Hoshino J, Fujii T, Usui J, Fujii T, Ohashi K, Takaichi K, Suzuki S, Ubara Y, Yamagata K. Renal outcome after tonsillectomy plus corticosteroid pulse therapy in patients with immunoglobulin A nephropathy: results of a multicenter cohort study. Clin Exp Nephrol. 2016;20:618–27.CrossRefGoogle Scholar
  32. 32.
    Reich HN, Troyanov S, Scholey JW, Cattran DC. Toronto glomerulonephritis registry. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007;18:3177–83.CrossRefGoogle Scholar
  33. 33.
    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. Corticosteroid treatment influences TA-proteinuria and renal survival in IgA nephropathy. PLoS One. 2016;14:e0158584.CrossRefGoogle Scholar
  34. 34.
    Suzuki Y, Matsuzaki K, Suzuki H, Sakamoto N, Joh K, Kawamura T, Tomino Y, Matsuo S. Proposal of remission criteria for IgA nephropathy. Clin Exp Nephrol. 2014;18:481–6.CrossRefGoogle Scholar
  35. 35.
    Moriyama T, Nakayama K, Iwasaki C, Ochi A, Tsuruta Y, Itabashi M, Tsukada M, Takei T, Uchida K, Nitta K. Severity of nephrotic IgA nephropathy according to the Oxford classification. Int Urol Nephrol. 2012;44:1177–84.CrossRefGoogle Scholar
  36. 36.
    Kim JK, Kim JH, Lee SC, Kang EW, Chang TI, Moon SJ, Yoon SY, Yoo TH, Kang SW, Choi KH, Han DS, Kie JH, Lim BJ, Jeong HJ, Han SH. Clinical features and outcomes of IgA nephropathy with nephrotic syndrome. Clin J Am Soc Nephrol. 2012;7:427–36.CrossRefGoogle Scholar
  37. 37.
    Szeto CC, Lai FM, To KF, Wong TY, Chow KM, Choi PC, Lui SF, Li PK. The natural history of immunoglobulin A nephropathy among patients with hematuria and minimal proteinuria. Am J Med. 2001;110:434–7.CrossRefGoogle Scholar
  38. 38.
    Shen P, He L, Li Y, Wang Y, Chan M. Natural history and prognostic factors of IgA nephropathy presented with isolated microscopic hematuria in Chinese patients. Nephron Clin Pract. 2007;106:157–61.CrossRefGoogle Scholar
  39. 39.
    Shen P, He L, Huang D. Clinical course and prognostic factors of clinically early IgA nephropathy. Neth J Med. 2008;66:242–7.Google Scholar
  40. 40.
    Gutiérrez E, Zamora I, Balları´n JA, Arce Y, Jime´nez S, Quereda C, Olea T, Martı´nez-Ara J, Segarra A, Bernis C, Garcı´a A, Goicoechea M, de Garcı´a-Vinuesa S, Rojas-Rivera J, Praga M, Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Espan˜ola de Nefrologı´a (GLOSEN). Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol. 2012;23:1753–60.CrossRefGoogle Scholar
  41. 41.
    Sevillano AM, Gutiérrez E, Yuste C, Cavero T, Mérida E, Rodríguez P, García A, Morales E, Fernández C, Martínez MA, Moreno JA, Praga M. Remission of Hematuria Improves Renal Survival in IgA Nephropathy. J Am Soc Nephrol. 2017;28:3089–99.CrossRefGoogle Scholar
  42. 42.
    Goto M, Kawamura T, Wakai K, Ando M, Endoh M, Tomino Y. Risk stratification for progression of IgA nephropathy using a decision tree induction algorithm. Nephrol Dial Transpl. 2009;24:1242–57.CrossRefGoogle Scholar
  43. 43.
    Tanaka K, Moriyama T, Iwasaki C, Takashi T, Nitta K. Effect of hematuria on the outcome of IgA nephropathy with minimal or no proteinuria. Clin Exp Nephrol. 2016;26:107–12.Google Scholar
  44. 44.
    Iwasaki C, Moriyama T, Tanaka K, Takei T, Nitta K. Effect of hematuria on the outcome of IgA nephropathy with proteinuria. J Nephropathol. 2016;5:72–8.CrossRefGoogle Scholar
  45. 45.
    Masuda Y, Yamanaka N, Ishikawa A, Kataoka M, Arai T, Wakamatsu K, Kuwahara N, Nagahama K, Ichikawa K, Shimizu A. Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy. Clin Exp Nephrol. 2015;19:427–35.CrossRefGoogle Scholar
  46. 46.
    Rashidbeygi E, Safabakhsh M, Delshad Aghdam S, Mohammed SH, Alizadeh S. Metabolic syndrome and its components are related to a higher risk for albuminuria and proteinuria: evidence from a meta-analysis on 10,603,067 subjects from 57 studies. Diabetes Metab Syndr. 2019;13:830–43.CrossRefGoogle Scholar
  47. 47.
    Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic syndrome and kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2011;6:2364–73.CrossRefGoogle Scholar
  48. 48.
    Syrjänen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricemia are risk factors for progression of IgA nephropathy. Nephrol Dialysis Transplant. 2000;15:34–42.CrossRefGoogle Scholar
  49. 49.
    Shimamoto M, Ohsawa I, Suzuki H, Hisada A, Nagamachi S, Honda D, Inoshita H, Shimizu Y, Horikoshi S, Tomino Y. Impact of body mass index on progression of IgA nephropathy among japanese patients. J Clin Lab Anal. 2015;29:353–60.CrossRefGoogle Scholar
  50. 50.
    D’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol. 2004;24:179–96.CrossRefGoogle Scholar
  51. 51.
    Johnson RJ, Nakagawa T, Jalal D, Sánchez-Lozada LG, Kang DH, Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013;28:2221–8.CrossRefGoogle Scholar
  52. 52.
    Zhu B, Yu DR, Lv JC, Lin Y, Li Q, Yin JZ, Du YY, Tang XL, Mao LC, Li QF, Sun Y, Liu L, Li XF, Fei D, Wei XY, Zhu CF, Cheng XX, Chen HY, Wang YJ. Uric Acid as a Predictor of Immunoglobulin A nephropathy progression: a cohort study of 1965 cases. Am J Nephrol. 2018;48:127–36.CrossRefGoogle Scholar
  53. 53.
    Moriyama T, Itabashi M, Takei T, Kataoka H, Sato M, Shimizu A, Iwabuchi Y, Nishida M, Uchida K, Nitta K. High uric acid level is a risk factor for progression of IgA nephropathy with chronic kidney disease stage G3a. J Nephrol. 2015;28:451–6.CrossRefGoogle Scholar
  54. 54.
    Komatsu H, Fujimoto S, Yoshikawa N, Kitamura H, Sugiyama H, Yokoyama H. Clinical manifestations of Henoch-Schönlein purpura nephritis and IgA nephropathy: comparative analysis of data from the Japan Renal Biopsy Registry (J-RBR). Clin Exp Nephrol. 2016;20:552–60.CrossRefGoogle Scholar
  55. 55.
    Nitta K, Okada K, Yanai M, Takahashi S. Aging and chronic kidney disease. Kidney Blood Press Res. 2013;38:109–20.CrossRefGoogle Scholar
  56. 56.
    Oshima Y, Moriyama T, Itabashi M, Takei T, Nitta K. Characteristics of IgA nephropathy in advanced-age patients. Int Urol Nephrol. 2015;47:137–45.CrossRefGoogle Scholar
  57. 57.
    Okabayashi Y, Tsuboi N, Haruhara K, Kanzaki G, Koike K, Shimizu A, Miyazaki Y, Ohno I, Kawamura T, Ogura M, Yokoo T. Reduction of proteinuria by therapeutic intervention improves the renal outcome of elderly patients with IgA nephropathy. Clin Exp Nephrol. 2016;20:910–7.CrossRefGoogle Scholar
  58. 58.
    Lee SM, Rao VM, Franklin WA, Schiffer MS, Aronson AJ, Spargo BH, Katz AI. IgA nephropathy: morphological predictors of progressive renal disease. Hum Pathol. 1982;13:314–22.CrossRefGoogle Scholar
  59. 59.
    Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997;29:829–42.CrossRefGoogle Scholar
  60. 60.
    Shigematsu H. Histological grading and staging of IgA nephropathy. Pathorol Int. 1997;47:194–202.CrossRefGoogle Scholar
  61. 61.
    Suzuki H. Biomarkers fo rIgA nephropathy on the basis of multi-hit pathogenesis. Clin Exp Nephrol. 2018.  https://doi.org/10.1007/s10157-018-1582-2 [Epub ahead of print].Google Scholar
  62. 62.
    Moriyama T, Shimizu A, Takei T, Uchida K, Honda K, Nitta K. Characteristics of immunoglobulin A nephropathy with mesangial immunoglobulin G and immunoglobulin M deposition. Nephrol (Carlton). 2010;15:747–54.CrossRefGoogle Scholar
  63. 63.
    Wada Y, Ogata H, Takeshige Y, Takeshima A, Yoshida N, Yamamoto M, Ito H, Kinugasa E. Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy. Clin Exp Nephrol. 2013;17:73–82.CrossRefGoogle Scholar
  64. 64.
    Shin DH, Lim BJ, Han IM, Han SG, Kwon YE, Park KS, Lee MJ, Oh HJ, Park JT, Han SH, Kang SW, Yoo TH. Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy. Mod Pathol. 2016;29:743–52.CrossRefGoogle Scholar
  65. 65.
    Suzuki H, Yasutake J, Makita Y, Tanbo Y, Yamasaki K, Sofue T, Kano T, Suzuki Y. IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis. Kidney Int. 2018;93:700–5.CrossRefGoogle Scholar
  66. 66.
    KDIGO clinical practice guidelines for glomerulonephritis-chapter 10: immunoglobulin A nephropathy. Kindey Int Supple 2012;2:S209–17.Google Scholar
  67. 67.
    Manno C, Torres DD, Rossini M, Pesce F, Schena FP. Randomized controlled clinical trial of corticosteroids plus ACE inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transpl. 2009;24:3694–701.CrossRefGoogle Scholar
  68. 68.
    Lv J, Zhang H, Chen Y, Li G, Jiang L, Singh AK, Wang H. Combination therapy of prednisolone and ACE inhibitor versus ACE inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis. 2009;53:26–32.CrossRefGoogle Scholar
  69. 69.
    Komatsu H, Fujimoto S, Hara S, Sato Y, Yamada K, Kitamura K. Effect of tonsillectomy plus steroid pulse therapy on clinical remission of IgA nephropathy: a controlled study. Clin J Am Soc Nephrol. 2008;3:1301–7.CrossRefGoogle Scholar
  70. 70.
    Ochi A, Moriyama T, Takei T, Uchida K, Nitta K. Comparison between steroid pulse therapy alone and in combination with tonsillectomy for IgA nephropathy. Int Urol Nephrol. 2013;45:469–76.CrossRefGoogle Scholar
  71. 71.
    Hoshino Y, Moriyama T, Uchida K, Tsuchiya K, Nitta K. Comparison of oral steroids with tonsillectomy plus steroid pulse therapy in patients with IgA nephropathy. Clin Exp Nephrol. 2017;21:617–23.CrossRefGoogle Scholar
  72. 72.
    Zhai YL, Zhu L, Shi SF, Liu LJ, Lv JC, Zhang H. Increased APRIL expression induces IgA1 aberrant glycosylation in IgA nephropathy. Med (Baltim). 2016;95:e3099.CrossRefGoogle Scholar
  73. 73.
    Kim YG, Alvarez M, Suzuki H, Hirose S, Izui S, Tomino Y, Huard B, Suzuki Y. Pathogenic role of a proliferation-inducing ligand (APRIL) in murine IgA nephropathy. PLoS ONE. 2015;10:e0137044.CrossRefGoogle Scholar
  74. 74.
    Goto T, Bandoh N, Yoshizaki T, Nozawa H, Takahara M, Ueda S, Hayashi T, Harabuchi Y. Increase in B-cell-activation factor (BAFF) and IFN-gamma productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy. Clin Immunol. 2008;126:260–9.CrossRefGoogle Scholar
  75. 75.
    Muto M, Manfroi B, Suzuki H, Joh K, Nagai M, Wakai S, Righini C, Maiguma M, Izui S, Tomino Y, Huard B, Suzuki Y. 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;28:1227–38.CrossRefGoogle Scholar
  76. 76.
    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 Group. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron. 2016;132:15–24.CrossRefGoogle Scholar
  77. 77.
    Watanabe H, Goto S, Kondo D, Takata T, Yamazaki H, Hosojima M, Yamamoto S, Kaneko Y, Aoyagi R, Narita I. Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients. Clin Exp Nephrol. 2017;21:257–65.CrossRefGoogle Scholar
  78. 78.
    Ieiri N, Hotta O, Sato T, Taguma Y. Significance of the duration of nephropathy for achieving clinical remission in patients with IgA nephropathy treated by tonsillectomy and steroid pulse therapy. Clin Exp Nephrol. 2012;16:122–9.CrossRefGoogle Scholar
  79. 79.
    Imai H, Miura N. A treatment dilemma in adult immunoglobulin A nephropathy: what is the appropriate target, preservation of kidney function or induction of clinical remission? Clin Exp Nephrol. 2012;16:195–201.CrossRefGoogle Scholar
  80. 80.
    Diaz Encarnacion MM, Warner GM, Cheng J, Gray CE, Nath KA, Grande JP. N-3 fatty acids block TNF-α-stimulated MCP-1 expression in rat mesangial cells. Am J Physiol Renal Physiol. 2011;300:F1132–51.CrossRefGoogle Scholar
  81. 81.
    Jia Q, Zhou HR, Bennink M, Pestka JJ. Docosahexaenoic acid attenuates mycotoxin-induced Immunoglobulin A nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice. J Neutr. 2004;134:3343–9.CrossRefGoogle Scholar
  82. 82.
    Piante G, Musacchio E, valvason C, Clari G, Bordin L, Sartori L, Naggio B. Further insights about the beneficial effects of n-3 fatty acids in the early molecular events of renal fibrosis in vitro. J Nephrol. 2013;26:652–9.CrossRefGoogle Scholar
  83. 83.
    Piante G, Musacchio E, Valvason C, Baggio B. EPA and DHA suppress Ang II- and arachidonic acid-induced expression of profibrotic genes in human mesangial cells. J Nephrol. 2009;22:137.Google Scholar
  84. 84.
    Pestka JJ, Zhou HR, Jia Q, Timmer AM. Dietary fish oil suppresses experimental immunoglobulin A nephropathy in mice. J Nutr. 2002;132:261–9.CrossRefGoogle Scholar
  85. 85.
    Jia Q, Shi Y, Bennink M, Pestka JJ. Docosahexaenoic acid and eicosapentaenoic acid, but not α-linolenic acid, suppress deoxynivalenol-induced experimental IgA nephropathy in mice. J Nutr. 2004;134:1353–61.CrossRefGoogle Scholar
  86. 86.
    Hamazaki T, Tateno S, Shishido M. Eicosapentaenoic acid and IgA nephropathy. Lancet. 1984;1:1017–8.CrossRefGoogle Scholar
  87. 87.
    Chou HH, Chiou YY, Hung PH, Chiang PC, Wang ST. Omega-3 fatty acids amerilrate proteinuria but not renal function in IgA nephropathy: a meta analysis of randomized controlled trials. Nephron Clin Pract. 2012;121:c30–5.CrossRefGoogle Scholar
  88. 88.
    Moriyama T, Iwasaki C, Tanaka K, Ochi A, Shimizu A, Shiohira S, Itabashi M, Takei T, Uchida K, Tsuchiya K, Nitta K. Effects of combination therapy with renin-angiotensin system inhibitors and eicosapentaenoic acid on IgA nephropathy. Intern Med. 2013;52:193–9.CrossRefGoogle Scholar
  89. 89.
    Moriyama T, Kumon S, Kamiyama T, Karasawa K, Uchida K, Nitta K. The renoprotective effects of docosahexaenoic acid as add-on therapy in patients receiving eicosapentaenoic acid as treatment for IgA nephropathy: a pilot uncontrolled trial. Intern Med. 2018;57:173–9.CrossRefGoogle Scholar
  90. 90.
    Su X, Zhang L, Lv J, Wang J, Hou W, Xie X, Zhang H. Effect of statins on kidney disease outcomes: a systematic review and meta-analysis. Am J Kidney Dis. 2016;67:881–92.CrossRefGoogle Scholar
  91. 91.
    Moriyama T, Oshima Y, Tanaka K, Iwasaki C, Ochi A, Itabashi M, Takei T, Uchida K, Nitta K. Statins stabilize the renal function of IgA nephropathy. Ren Fail. 2014;36:356–60.CrossRefGoogle Scholar
  92. 92.
    Buemi M, Allegra A, Corica F, Aloisi C, Giacobbe M, Pettinato G, Corsonello A, Senatore M, Frisina N. Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy. Clin Pharmacol Ther. 2000;67:427–31.CrossRefGoogle Scholar
  93. 93.
    Kano K, Nishikura K, Yamada Y, Arisaka O. Effect of fluvastatin and dipyridamole on proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria. Clin Nephrol. 2003;60:85–9.CrossRefGoogle Scholar
  94. 94.
    Lundberg S, Lundahl J, Gunnarsson I, Jacobson SH. Atorvastatininduced modulation of monocyte respiratory burst in vivo patients with IgA nephropathy: a chronic inflammatory kidney disease. Clin Nephrol. 2010;73:221–8.CrossRefGoogle Scholar
  95. 95.
    Nakamura T, Ushiyama C, Hirokawa K, et al. Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis. Nephrol Dial Transpl. 2002;17:798–802.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  1. 1.Department of NephrologyTokyo Women’s Medical UniversityTokyoJapan

Personalised recommendations