Advertisement

The Differences in Etiology and Treatment of IgA Nephropathy in Korea

  • Dong-Wan ChaeEmail author
Chapter

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulonephritis affecting young persons, the incidence of which has increased recently in Korea. Many studies related to the etiology and the pathogenesis such as various biomarkers, gene polymorphism, and intrarenal expression of various cytokines and chemokines and proteomic studies have been performed in serum, urine, and renal tissues obtained from Korean patients with IgA nephropathy. The activation of alternative pathway of complements in systemic circulation as well as local mesangial area and the activation of lectin and classic pathway of complement in some subset of patients have been shown to contribute to renal damage in IgAN. Clinical utility of Oxford classification have been verified in Korean patients, but the significance of crescent in therapeutic response and prognosis remains to be defined especially in patients with low basal estimated glomerular filtration rate (eGFR) and/or patients on the immunosuppressive therapy at the time of renal biopsy. The maintenance of proteinuria <1 g/day as recommended by KDIGO was a reasonable therapeutic target in renal protection, but the attainment of proteinuria <0.3 g/day might provide additional renal protection especially in young and otherwise healthy patients in whom a long life span is expected. Renin-angiotensin system (RAS) blockades reduced proteinuria and improved the survival of patients as well as the kidney. Various regimens of corticosteroid treatments effectively reduced proteinuria and hematuria and induced the improvement or stabilization of renal function even in patients with already decreased eGFR before treatment. Treatments by calcineurin inhibitors and sulodexide in IgAN were also reported with some positive results.

Keywords

IgA nephropathy Korea Pathogenesis Treatment 

Notes

Conflict of Interest

The author declares that he has no conflict of interest.

References

  1. 1.
    Jae Hyun Chang, Dong Ki Kim, Hyun Wook Kim, Sun Young Park, Tae-Hyun Yoo, Beom Seok Kim, et al. Changing prevalence of glomerular diseases in Korean adults: a review of 20 years of experience. Nephrol Dial Transplant. 2009;31:2406. doi: 10.1093/ndt/gfp091.
  2. 2.
    Park JS, Song JH, Yang WS, Kim SB, Kim YK, Hong CD. Cytomegalovirus is not specifically associated with immunoglobulin A nephropathy. J Am Soc Nephrol. 1994;4:1623.PubMedGoogle Scholar
  3. 3.
    Gyung Geun Han, Jeong Ha Pack, Sung Jin Bae, Sam Ryong Ji, Jeong Hyun Lim, Goang Yul Jang, et al. A clinical study of IgA nephropathy with serum Hepatitis B surface antigen. Korean J Nephrol. 2000;19:437.Google Scholar
  4. 4.
    Jwa Kyung Kim, Jeong Ho Kim, Sang Choel Lee, Ea Wha Kang, Tae Ik Chang, Sung Jin Moon, et al. Clinical features and outcomes of IgA nephropathy with nephrotic syndrome. Clin J Am Soc Nephrol. 2012;7:427. doi: 10.2215/CJN.04820511.
  5. 5.
    In O Sun, Yu Ah Hong, Hoon Suk Park, Sun Ryoung Choi, Byung Ha Chung, Cheol Whee Park, et al. Clinical characteristics and treatment of patients with IgA nephropathy and hepatitis B surface antigen. Ren Fail. 2013;35:446. doi: 10.3109/0886022X.
  6. 6.
    Seung Hyeok Han, Ea Wha Kang, Jeong Hae Kie, Tae Hyun Yoo, Kyu Hun Choi, Dae-Suk Han, et al. Spontaneous remission of IgA nephropathy associated with resolution of Hepatitis A. Am J Kidney Dis. 2010;56:1163. doi: 10.1053/j.ajkd.2010.08.018.
  7. 7.
    Chun Soo Lim, Shouhuan Zheng, Yon Su Kim, Curie Ahn, Jin Suk Han, Suhnggwon Kim, et al. Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy. Nephrol Dial Transplant. 2001;16:269. doi: 10.1093/ndt/16.2.269.
  8. 8.
    Chun Soo Lim, Hyung Jin Yoon, Yon Su Kim, Curie Ahn, Jin Suk Han, Suhnggwon Kim, et al. Clinicopathological correlation of intrarenal cytokines and chemokines in IgA nephropathy. Nephrology (Carlton). 2003;8:21. doi: 10.1046/j.1440-1797.2003.00128.x.
  9. 9.
    Mi Ra Park, Eun Hui Wang, Dong Chan Jin, Jung Ho Cha, Kweon Heang Lee, Chul Woo Yang, et al. Establishment of a 2-D human urinary proteomic map in IgA nephropathy. Proteomics. 2006;6:1066. doi: 10.1002/pmic.200500023.
  10. 10.
    Pyong-Gon Moon, Jeong-Eun Lee, Sungyong You, Taek-Kyun Kim, Ji-Hoon Cho, In-San Kim, et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. Proteomics. 2011;11:2459. doi: 10.1002/pmic.201000443.
  11. 11.
    Noh Jin Kwak, Eun Hui Wang, Il-Young Heo, Dong-Chan Jin, Jung-Ho Cha, Kweon-Haeng Lee, et al. Proteomic analysis of alpha-1-antitrypsin in immunoglobulin A nephropathy. Proteomics Clin Appl. 2007;1:420. doi: 10.1002/prca.200600288.
  12. 12.
    Soon Hyo Kwon, Moo Yong Park, Jin Seok Jeon, Hyunjin Noh, Soo Jeong Choi, Jin Kuk Kim, et al. KIM-1 expression predicts renal outcomes in IgA nephropathy. Clin Exp Nephrol. 2013;17:359. doi: 10.1007/s10157-012-0707-2.
  13. 13.
    Ji Hye Lee, Mee Hye Oh, Jae Seok Park, Gyoung Jae Na, Hye Wook Gil, Jong Oh Yang, et al. Urokinase, urokinase receptor, and plasminogen activator inhibitor-1 expression on podocytes in immunoglobulin A glomerulonephritis. Korean J Intern Med. 2014;29:176. doi: 10.3904/kjim.2014.29.2.176.
  14. 14.
    Jae Ryung Shin, Seung Min Kim, Jung Sun Yoo, Ji Yoon Park, Seul Ki Kim, Joo Hee Cho, et al. Urinary excretion of β2-microglobulin as a prognostic marker in immunoglobulin A nephropathy. Korean J Intern Med. 2011;29:334–40. doi: 10.3904/kjim.2014.29.3.334
  15. 15.
    Ho Jun Chin, Hyun Jin Cho, Tae Woo Lee, Ki Young Na, Hyung Jin Yoon, Dong-Wan Chae, et al. The Heme Oxygenase-1 Genotype is a risk factor to renal impairment of IgA nephropathy at diagnosis, which is a strong predictor of mortality. J Korean Med Sci. 2009;24 Suppl:S30. doi: 10.3346/jkms.2009.24.S1.S30.
  16. 16.
    Ho Jun Chin, Hyun Jin Cho, Tae Woo Lee, Ki Young Na, Kook Hwan Oh, Kwon Wook Joo, et al. The mildly elevated serum bilirubin level is negatively associated with the incidence of end stage renal disease in patients with IgA nephropathy. J Korean Med Sci. 2009;24 Suppl:S22. doi: 10.3346/jkms.2009.24.S1.S22.
  17. 17.
    Hye Ryoun Jang, Soo Min Park, Yu ji Lee, Jung Eun Lee, Woo Seong Huh, Dae Joong Kim, et al. The origin and the clinical significance of urinary angiotensinogen in proteinuric IgA nephropathy patients. Ann Med. 2012;44:448. doi: 10.3109/07853890.2011.558518.
  18. 18.
    Sun Moon Kim, Ho Jun Chin, Yun Kyu Oh, Yon Su Kim, Suhnggwon Kim, Chun Soo Lim. Blood pressure-related genes and the progression of IgA nephropathy. Nephron Clin Pract 2009;113:c301. doi: 10.1159/000235948.
  19. 19.
    HJ Yoon, H Kim, HL Kim, SG Lee, S H Zheng, JH Shi, et al. Interdependent effect of angiotensin-converting enzyme and platelet-activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy. Clin Genet. 2002;62:128. doi: 10.1034/j.1399-0004.2002.620205.x.
  20. 20.
    Eun Sook Jung, Sun Moon Kim, Ho Jun Chin, Ran Hui Cha, Yun Kyu Oh, Yon Su Kim, et al. Impact of polymorphisms of the genes encoding angiotensin II-forming enzymes on the progression of IgA nephropathy. Nephron Clin Pract 2011;118:c122. doi: 10.1159/000321140.
  21. 21.
    Hyung Jin Yoon, Ho Jun Chin, Ki Young Na, Dong Wan Chae, Suhnggwon Kim, Un Sil Jeon, et al. Association of angiotensin II Type 2 receptor gene A1818T polymorphism with progression of Immunoglobulin A nephropathy in Korean Patients. J Korean Med Sci. 2009;24 Suppl:S38. doi: 10.3346/jkms.2009.24.S1.S38.
  22. 22.
    CS Lim, SM Kim, YK Oh, YS Kim, DW Chae, JS Han, et al. Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy. Clin Nephrol. 2007; 67:73.Google Scholar
  23. 23.
    Yoon HJ, Shin JH, Yang SH, Chae DW, Kim H, Lee DS, et al. Association of the CD14 gene-159C polymorphism with progression of IgA nephropathy. J Med Genet. 2003;40:104. doi: 10.1136/jmg.40.2.104.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lim CS, Kim SM, Oh YK, Joo KW, Kim YS, Han JS, et al. Megsin 2093T-2180C haplotype at the 3′ untranslated region in associated with poor renal survival in Korean IgA nephropathy patients. Clin Nephrol. 2008;70:101.CrossRefPubMedGoogle Scholar
  25. 25.
    Lim CS, Kim YS, Chae DW, Ann C, Han JS, Kim S. Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with susceptibility to and progression of IgA nephropathy. Clin Nephrol. 2005;63:61.CrossRefPubMedGoogle Scholar
  26. 26.
    Jung Pyo Lee, Seung Hee Yang, Dong Ki Kim, Hajeong Lee, Bora Kim, Joo Youn Cho, et al. In vivo activity of epoxide hydrolase according to sequence variation affects the progression of human IgA nephropathy. Am J Physiol Renal Physiol. 2011;300:F1283. doi: 10.1152/ajprenal.00733.2010.
  27. 27.
    Gang Jae Ko, Eun Ah Lee, Un Sil Jeon, Heui Jung Pyo, Ho Jun Chin, Dong Wan Chae, et al. The association of Klotho Polymorphism with disease progression and mortality in IgA nephropathy. Kidney Blood Press Res. 2012;36:191. doi: 10.1159/000343408.
  28. 28.
    Lee HS, Koh HI, Lee HB, Park HC. IgA nephropathy in Korea: a morphological and clinical study. Clin Nephrol. 1987;27:131.PubMedGoogle Scholar
  29. 29.
    Seung Jun Kim, Hyang Mo Koo, Beom Jin Lim, Hyung Jung Oh, Dong Eun Yoo, Dong Ho Shin, et al. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS One. 2012;7:e40495. doi: 10.1371/journal.pone.0040495.
  30. 30.
    Young In Maeng, Min Kyung Kim, Jae Bok Park, Chang Ho Cho, Hoon Kyu Oh, Woo Jung Sung, et al. Glomerular and tubular C4d depositions in IgA nephropathy: relations with histopathology and with albuminuria. Int J Clin Exp Pathol. 2013;6:904.Google Scholar
  31. 31.
    Hong Joo Lee, So Young Choi, Kyung Hwan Jeong, Ji Youn Sung, Sung Kyoung Moon, Ju Young Moon, et al. Association of C1q deposition with renal outcomes in IgA nephropathy. Clin Nephrol. 2013;80:98. doi: 10.5414/CN107854.
  32. 32.
    Hyun Soon Lee, Myung Suk Lee, Sa Min Lee, Sang Yun Lee, Eun Sun Lee, Eun Young Lee, et al. Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee’s glomerular grading system. Nephrol Dial Transplant. 2005;20:342.Google Scholar
  33. 33.
    Shin Wook Kang, Kyu Hun Choi, Jong Hoon Park, Seung Woo Lee, Ho Yung Lee, Dae Suk Han, et al. Prognostic factors and renal survival rates in IgA nephropathy. Yonsei Med J. 1995;36:45.Google Scholar
  34. 34.
    Seok Hui Kang, Sun Ryoung Choi, Hoon Suk Park, Ja Young Lee, In O Sun, Hyeon Seok Hwang, et al. The Oxford classification as a predictor of prognosis in patients with IgA nephropathy. Nephrol Dial Transplant. 2012;27:252. doi: 10.1093/ndt/gfr295.
  35. 35.
    Ho young Lee, Sul Hee Yi, Mi Seon Seo, Jin Nam Hyun, Jin Seok Jeon, Hyunjin Noh, et al. Validation of the Oxford classification of IgA nephropathy: a single-center study in Korean adults. Korean J Intern Med. 2012;27:293.Google Scholar
  36. 36.
    Kyoung Sook Park, Seung Hyeok Han, Jeong Hae Kie, Ki Heon Nam, Mi Jung Lee, Beom Jin Lim, et al. Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy. Hum Pathol. 2014;45:236. doi: 10.1016/j.humpath.2013.08.019.
  37. 37.
    Beom Jin Lim, Dong Jin Joo, Myoung Soo Kim, Yu Seun Kim, Soon Il Kim, Yeon hee Kim, et al. Usefulness of Oxford classification in assessing immunoglobulin A nephropathy After Transplantation. Transplantation. 2013;95:1491. doi: 10.1097/TP.0b013e318291de65.
  38. 38.
    Mi Jung Lee, Seung Jun Kim, Hyung Jung Oh, Kwang Il Ko, Hyang Mo Koo, Chan Ho Kim, et al. Clinical implication of crescentic lesions in immunoglobulin A nephropathy. Nephrol Dial Transplant. 2014;29:356. doi: 10.1093/ndt/gft398.
  39. 39.
    Hyeon Joo Jeong, Yu Seun Kim, Ki Hwan Kwon, Soon Il Kim, Myoung Soo Kim, Kyu Hun Choi et al. Glomerular crescents are responsible for chronic graft dysfunction in post-transplant IgA nephropathy. Pathol Int. 2004;54:837.Google Scholar
  40. 40.
    Byung Soo Kim, Yong Kyun Kim, Young Shin Shin, Young Ok Kim, Ho Cheol Song, Yong Soo Kim, et al. Natural history and renal pathology in patients with isolated microscopic hematuria. Korean J Intern Med. 2009;24:356. doi: 10.3904/kjim.2009.24.4.356.
  41. 41.
    Hajeong Lee, Jin Ho Hwang, Jin Ho Paik, Hyun Jin Ryu, Dong Ki Kim, Ho Jun Chin, et al. Long-term prognosis of clinically early IgA nephropathy is not always favorable. BMC Nephrol. 2014;15:94. doi: 10.1186/1471-2369-15-94.
  42. 42.
    Sun Moon Kim, Kyung Chul Moon, Kook-Hwan Oh, Kwon Wook Joo, Yon Su Kim, Curie Ahn, et al. Clinicopathologic characteristics of IgA nephropathy with steroid-responsive nephrotic syndrome. J Korean Med Sci. 2009;24 Suppl:S44. doi: 10.3346/jkms.2009.24.S1.S44.
  43. 43.
    Ki Heon Nam, Jeong Hae Kie, Mi Jung Lee, Tae-Ik Chang, Ea Wha Kang, Dong Wook Kim, et al. Optimal proteinuria target for renoprotection in patients with IgA nephropathy. PLoS One. 2014;9(7):e101935. doi: 10.1371/journal.pone.0101935.
  44. 44.
    Hyeon Seok Hwang, Byung Soo Kim, Young Shin Shin, Hye Eun Yoon, Joon Chang Song, Bum Soon Choi, et al. Predictors for progression in immunoglobulin A nephropathy with significant proteinuria. Nephrology (Carlton). 2010;15:236. doi: 10.1111/j.1440-1797.2009.01196.x.
  45. 45.
    You Cheol Hwang, Tae Won Lee, Myung Jae Kim, Moon Ho Yang, Chun Gyoo Ihm. Clinical course of patients with IgA nephropathy between combined treatment of immunosuppressive agents and ACE Inhibitor and ACE Inhibitor alone. Korean J Intern Med. 2001;16:105.Google Scholar
  46. 46.
    Han SY, Kwon YJ, Jo SK, Shin JH, Cha DR, Cho WY, et al. ACE gene polymorphism and renal responsiveness to ACE inhibitors in IgA nephropathy patients. Korean J Intern Med. 2000;15:13.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hyeong Cheon Park, Zhong Gao Xu, Sorae Choi, Young Suck Goo, Shin Wook Kang, Kyu Hun Choi, et al. Effect of losartan and amlodipine on proteinuria and transforming growth factor‐β1 in patients with IgA nephropathy. Nephrol Dial Transplant. 2003;18:1115. doi: 10.1093/ndt/gfg090.
  48. 48.
    Moon Jae Kim, Joon Ho Song, Ju Hyun Suh, Seoung Woo Lee, Gyoung A Kim. Additive antiproteinuric effect of combination therapy with ACE inhibitor and angiotensin II receptor antagonist: differential short-term response between IgA nephropathy and diabetic nephropathy. Yonsei Med J. 2003;44:463.Google Scholar
  49. 49.
    Song JH, Lee SW, Suh JH, Kim ES, Hong SB, Kim KA, et al. The effects of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy. Clin Nephrol. 2003;60:318.CrossRefPubMedGoogle Scholar
  50. 50.
    Hyeon Joo Jeong, Yu Seun Kim, Kye Won Kwon, Myoung Soo Kim, Soon Kim, Kyu Hun Choi, et al. Segmental glomerulosclerosis in IgA nephropathy after renal transplantation: relationship with proteinuria and therapeutic response to enalapril. Clin Transplant. 2003;17:108. doi: 10.1034/j.1399-0012.2003.02067.x.
  51. 51.
    Choi S, Lee D, Jeong KH, Moon JY, Lee SH, Lee TW, et al. Prognostic relevance of clinical and histological features in IgA nephropathy treated with steroid and angiotensin receptor blockers. Clin Nephrol. 2009;72:353. doi: 10.5414/CNP72353.CrossRefPubMedGoogle Scholar
  52. 52.
    Ji Min Jeong, Dae Hun Lim, Hyung Chul Lee, Seul Hyun Oh, Joon Seok Choi, Pyung Kyun Park, et al. Renoprotective effect of deflazacort in IgA nephropathy with proteinuria. Korean J Med. 2009;7:593.Google Scholar
  53. 53.
    Tae Young Kim, Soon Bae Kim, Su-Kil Park. The efficacy of steroid pulse therapy in patients with IgA nephropathy. Clin Nephrol. 2012;78:100. doi: 10.5414/CN107418.
  54. 54.
    Hyung Jung Oh, Song Vogue Ahn, Dong Eun Yoo, Seung Jun Kim, Dong Ho Shin, Mi Jung Lee, et al. Clinical outcomes, when matched at presentation, do not vary between adult-onset Henöch-Schönlein purpura nephritis and IgA nephropathy. Kidney Int. 2012;82:1304. doi: 10.1038/ki.2012.302.
  55. 55.
    Yong Chul Kim, Ho Jun Chin, Ho Suk Koo, Suhnggwon Kim. Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy. PLoS One. 2013;8:e71545. doi: 10.1371/journal.pone.0071545.
  56. 56.
    Jae Il Shin, Beom Jin Lim, Pyung Kil Kim, Jae Seung Lee, Hyeon Joo Jeong, Ji Hong Kim. Effects of cyclosporin A therapy combined with steroids and angiotensin converting enzyme inhibitors on childhood IgA nephropathy. J Korean Med Sci. 2010;25:723. doi: 10.3346/jkms.2010.25.5.723.
  57. 57.
    Byeong Yun Yang, Hee Seon Lee, Sang Heon Song, Ihm Soo Kwak, Soo Bong Lee, Dong Won Lee, et al. Use of low-dose sulodexide in IgA nephropathy patients on renin–angiotensin system blockades. Kidney Res Clin Pract 2012;31:163.Google Scholar
  58. 58.
    Kitae Bang, Ho Jun Chin, Dong Wan Chae, Kwon Wook Joo, Yon Su Kim, Suhnggwon Kim, et al. Anti-proteinuric effect of sulodexide in immunoglobulin A nephropathy. Yonsei Med J. 2011;52:588. doi: 10.3349/ymj.2011.52.4.588.
  59. 59.
    Hajeong Lee, Dong Ki Kim, Kook-Hwan Oh, Kwon Wook Joo, Yon Su Kim, Dong-Wan Chae, et al. Mortality of IgA nephropathy patients: a single center experience over 30 years. PLoS One. 2012;7:e51225. doi: 10.1371/journal.pone.0051225.
  60. 60.
    Hajeong Lee, Dong Ki Kim, Kook-Hwan Oh, Kwon Wook Joo, Yon Su Kim, Dong-Wan Chae, et al. Mortality and renal outcome of primary glomerulonephritis in Korea: observation in 1,943 biopsied cases. Am J Nephrol 2013;37:74. doi: 10.1159/000345960.

Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Division of NephrologySeoul National University Bundang Hospital, Department of Internal Medicine, Seoul National College of MedicineSeongnam-siSouth Korea

Personalised recommendations