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  • Review Article
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Treatment of IgA nephropathy and Henoch–Schönlein nephritis

Nature Reviews Nephrology volume 9, pages 320–327 (2013)Cite this article

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Abstract

Treatment options for primary IgA nephropathy (IgAN) and Henoch–Schönlein nephritis are still largely based on opinion or weak evidence. Consequently, the recent KDIGO Clinical Practice Guidelines for Glomerulonephritis have assigned low levels of evidence for almost all recommendations and suggestions related to these two diseases. In this Review, we describe an algorithm for structuring the treatment of IgAN depending on the clinical scenario. Key to therapeutic decision making is assessment of the individual's prognosis. Clinical parameters (such as proteinuria, hypertension, and impaired glomerular filtration rate [GFR]) are used to estimate risk, but the clinical value of the novel histological Oxford-MEST classification remains to be determined. If these parameters indicate a risk of progressive GFR loss, comprehensive supportive care remains the mainstay of therapy. Two large trials, STOP-IgAN and TESTING, are underway to evaluate the value of adding corticosteroids after initiating such supportive care. At present, little evidence exists to suggest that any other immunosuppressive therapy beyond corticosteroids is effective in either IgAN or Henoch–Schönlein nephritis.

Key Points

  • Only a fraction of patients with IgA nephropathy require treatment in order to prevent or reduce progressive loss of glomerular filtration rate (GFR)

  • Proteinuria, hypertension and any evidence of established renal damage enable a relatively reliable estimation of patient risk

  • The 'low-risk' patient with minor urinary abnormalities, normal GFR and normotension requires regular follow-up only

  • The 'intermediate-risk' patient with 'significant' proteinuria, hypertension and/or a slow reduction in GFR (including those with an estimated GFR below 30 ml/min/1.73 m2) will benefit from comprehensive supportive care

  • Several ongoing studies will re-evaluate the role of systemic or enteric corticosteroids in 'intermediate-risk' patients

  • The 'high-risk' patient with a rapid loss of GFR may require more aggressive immunosuppression

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Figure 1: Suggested treatment algorithm for patients with primary IgAN depending on their initial presentation.

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References

  1. McGrogan, A., Franssen, C. F. & de Vries, C. S. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol. Dial. Transplant. 26, 414–430 (2011).

    Article  PubMed  Google Scholar 

  2. Kiryluk, K., Novak, J. & Gharavi, A. G. Pathogenesis of immunoglobulin A nephropathy: recent insight from genetic studies. Annu. Rev. Med. 64, 339–356 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Feehally, J. & Cameron, J. S. IgA nephropathy: progress before and since Berger. Am. J. Kidney Dis. 58, 310–319 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. Pouria, S. & Barratt, J. Secondary IgA nephropathy. Semin. Nephrol. 28, 27–37 (2008).

    Article  PubMed  Google Scholar 

  5. Rivera, F., Lopez-Gomez, J. M. & Perez-Garcia, R. Clinicopathologic correlations of renal pathology in Spain. Kidney Int. 66, 898–904 (2004).

    Article  PubMed  Google Scholar 

  6. Waldherr, R., Rambausek, M., Duncker, W. D. & Ritz, E. Frequency of mesangial IgA deposits in a non-selected autopsy series. Nephrol. Dial. Transplant. 4, 943–946 (1989).

    Article  CAS  PubMed  Google Scholar 

  7. Suzuki, K. et al. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 63, 2286–2294 (2003).

    Article  PubMed  Google Scholar 

  8. Yoshikawa, N. et al. Repeat renal biopsy in children with IgA nephropathy. Clin. Nephrol. 33, 160–167 (1990).

    CAS  PubMed  Google Scholar 

  9. Cuevas, X., Lloveras, J., Mir, M., Aubia, J. & Masramon, J. Disappearance of mesangial IgA deposits from the kidneys of two donors after transplantation. Transplant. Proc. 19, 2208–2209 (1987).

    CAS  PubMed  Google Scholar 

  10. Gutierrez, E. et al. Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J. Am. Soc. Nephrol. 23, 1753–1760 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Szeto, C. C. et al. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am. J. Med. 110, 434–437 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Hotta, O., Furuta, T., Chiba, S., Tomioka, S. & Taguma, Y. Regression of IgA nephropathy: a repeat biopsy study. Am. J. Kidney Dis. 39, 493–502 (2002).

    Article  PubMed  Google Scholar 

  13. Radford, M. G. Jr, Donadio, J. V. Jr, Bergstralh, E. J. & Grande, J. P. Predicting renal outcome in IgA nephropathy. J. Am. Soc. Nephrol. 8, 199–207 (1997).

    PubMed  Google Scholar 

  14. D'Amico, G. et al. Prognostic indicators in idiopathic IgA mesangial nephropathy. Q. J. Med. 59, 363–378 (1986).

    CAS  PubMed  Google Scholar 

  15. Berthoux, F. et al. Predicting the risk for dialysis or death in IgA nephropathy. J. Am. Soc. Nephrol. 22, 752–761 (2011).

    Article  PubMed  Google Scholar 

  16. Reich, H. N., Troyanov, S., Scholey, J. W. & Cattran, D. C. Remission of proteinuria improves prognosis in IgA nephropathy. J. Am. Soc. Nephrol. 18, 3177–3183 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Le, W. et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol. Dial. Transplant. 27, 1479–1485 (2012).

    Article  CAS  PubMed  Google Scholar 

  18. Bonnet, F. et al. Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. Am. J. Kidney Dis. 37, 720–727 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Yamamoto, R. et al. Cigarette smoking and progression of IgA nephropathy. Am. J. Kidney Dis. 56, 313–324 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Cattran, D. C. et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 76, 534–545 (2009).

    Article  PubMed  Google Scholar 

  21. Herzenberg, A. M. et al. Validation of the Oxford classification of IgA nephropathy. Kidney Int. 80, 310–317 (2011).

    Article  PubMed  Google Scholar 

  22. Zeng, C. H. et al. A multicenter application and evaluation of the Oxford classification of IgA nephropathy in adult chinese patients. Am. J. Kidney Dis. 60, 812–820 (2012).

    Article  PubMed  Google Scholar 

  23. Edstrom Halling, S., Soderberg, M. P. & Berg, U. B. Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification). Nephrol. Dial. Transplant. 27, 715–722 (2012).

    Article  PubMed  Google Scholar 

  24. Yau, T., Korbet, S. M., Schwartz, M. M. & Cimbaluk, D. J. The Oxford classification of IgA nephropathy: a retrospective analysis. Am. J. Nephrol. 34, 435–444 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. Shima, Y. et al. Validity of the Oxford classification of IgA nephropathy in children. Pediatr. Nephrol. 27, 783–792 (2012).

    Article  PubMed  Google Scholar 

  26. Kang, S. H. et al. The Oxford classification as a predictor of prognosis in patients with IgA nephropathy. Nephrol. Dial. Transplant. 27, 252–258 (2012).

    Article  PubMed  Google Scholar 

  27. ERA-EDTA. Advances in the European Validation Study of the Oxford Classification of IgA Nephropathy (VALIGA) [online], (2011).

  28. Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. Suppl. 2, 139–274 (2012).

  29. Vleming, L. J. et al. Histomorphometric correlates of renal failure in IgA nephropathy. Clin. Nephrol. 49, 337–344 (1998).

    CAS  PubMed  Google Scholar 

  30. Alamartine, E. et al. The use of the Oxford classification of IgA nephropathy to predict renal survival. Clin. J. Am. Soc. Nephrol. 6, 2384–2388 (2011).

    Article  PubMed  Google Scholar 

  31. Lundberg, S., Lundahl, J., Gunnarsson, I., Sundelin, B. & Jacobson, S. H. Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy. Nephrol. Dial. Transplant. 27, 1916–1923 (2012).

    Article  CAS  PubMed  Google Scholar 

  32. Lundberg, S. et al. FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. Clin. J. Am. Soc. Nephrol. 7, 727–734 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Vuong, M. T. et al. Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney Int. 78, 1281–1287 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Ranieri, E., Gesualdo, L., Petrarulo, F. & Schena, F. P. Urinary IL-6/EGF ratio: a useful prognostic marker for the progression of renal damage in IgA nephropathy. Kidney Int. 50, 1990–2001 (1996).

    Article  CAS  PubMed  Google Scholar 

  35. Torres, D. D. et al. The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy. Kidney Int. 73, 327–333 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Zwirner, J. et al. Activated complement C3: a potentially novel predictor of progressive IgA nephropathy. Kidney Int. 51, 1257–1264 (1997).

    Article  CAS  PubMed  Google Scholar 

  37. Janssen, U. et al. Activation of the acute phase response and complement C3 in patients with IgA nephropathy. Am. J. Kidney Dis. 35, 21–28 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Liu, L. L., Jiang, Y., Wang, L. N. & Liu, N. Urinary mannose-binding lectin is a biomarker for predicting the progression of immunoglobulin (Ig)A nephropathy. Clin. Exp. Immunol. 169, 148–155 (2012).

    Article  CAS  PubMed  Google Scholar 

  39. Rocchetti, M. T. et al. Urine protein profile of IgA nephropathy patients may predict the response to ACE-inhibitor therapy. Proteomics 8, 206–216 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Haubitz, M. et al. Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy. Kidney Int. 67, 2313–2320 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. El Karoui, K. et al. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. J. Am. Soc. Nephrol. 23, 137–148 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Roos, A. et al. 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 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Kataoka, H., Ohara, M., Honda, K., Mochizuki, T. & Nitta, K. Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy. Nephrol. Dial. Transplant. 26, 3937–3943 (2011).

    Article  PubMed  Google Scholar 

  44. Coppo, R. & D'Amico, G. Factors predicting progression of IgA nephropathies. J. Nephrol. 18, 503–512 (2005).

    PubMed  Google Scholar 

  45. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. Suppl. 2, 340–414 (2012).

  46. Floege, J. & Eitner, F. Current therapy for IgA nephropathy. J. Am. Soc. Nephrol. 22, 1785–1794 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Wilmer, W. A. et al. Management of glomerular proteinuria: a commentary. J. Am. Soc. Nephrol. 14, 3217–3232 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Abboud, H. & Henrich, W. L. Clinical practice. Stage IV chronic kidney disease. N. Engl. J. Med. 362, 56–65 (2010).

    Article  PubMed  Google Scholar 

  49. Praga, M., Gutierrez, E., Gonzalez, E., Morales, E. & Hernandez, E. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J. Am. Soc. Nephrol. 14, 1578–1583 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Coppo, R. et al. IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J. Am. Soc. Nephrol. 18, 1880–1888 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Li, P. K. et al. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am. J. Kidney Dis. 47, 751–760 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Tanaka, H. et al. Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy. Pediatr. Int. 46, 576–579 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Russo, D. et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am. J. Kidney Dis. 38, 18–25 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Eitner, F., Ackermann, D., Hilgers, R. D. & Floege, J. Supportive Versus Immunosuppressive Therapy of Progressive IgA nephropathy (STOP) IgAN trial: rationale and study protocol. J. Nephrol. 21, 284–289 (2008).

    CAS  PubMed  Google Scholar 

  55. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  56. Scholl, U. et al. The “point of no return” and the rate of progression in the natural history of IgA nephritis. Clin. Nephrol. 52, 285–292 (1999).

    CAS  PubMed  Google Scholar 

  57. D'Amico, G., Ragni, A., Gandini, E. & Fellin, G. Typical and atypical natural history of IgA nephropathy in adult patients. Contrib. Nephrol. 104, 6–13 (1993).

    Article  CAS  PubMed  Google Scholar 

  58. Ota, F., Ueki, K., Naruse, T. & Nojima, Y. Patients with IgA nephropathy whose renal function remains stable for a long time even after exceeding the “point of no return”. Clin. Nephrol. 54, 175–176 (2000).

    CAS  PubMed  Google Scholar 

  59. Hou, F. F. et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N. Engl. J. Med. 354, 131–140 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Ballardie, F. W. & Roberts, I. S. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J. Am. Soc. Nephrol. 13, 142–148 (2002).

    CAS  PubMed  Google Scholar 

  61. Uhlig, K. et al. Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 70, 2058–2065 (2006).

    Article  CAS  PubMed  Google Scholar 

  62. Katafuchi, R. et al. Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy. Am. J. Kidney Dis. 41, 972–983 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Hogg, R. J. et al. Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. Clin. J. Am. Soc. Nephrol. 1, 467–474 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Pozzi, C. et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J. Am. Soc. Nephrol. 15, 157–163 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Pozzi, C. et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353, 883–887 (1999).

    Article  CAS  PubMed  Google Scholar 

  66. Manno, C., Torres, D. D., Rossini, M., Pesce, F. & Schena, F. P. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol. Dial. Transplant. 24, 3694–3701 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Lv, J. et al. Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am. J. Kidney Dis. 53, 26–32 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Eitner, F. & Floege, J. Glomerular disease: ACEIs with or without corticosteroids in IgA nephropathy? Nat. Rev. Nephrol. 6, 252–254 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Drescher, W., Schlieper, G., Floege, J. & Eitner, F. Steroid-related osteonecrosis—an update. Nephrol. Dial. Transplant. 26, 2728–2731 (2011).

    Article  CAS  PubMed  Google Scholar 

  70. Pozzi, C. et al. Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J. Am. Soc. Nephrol. 21, 1783–1790 (2010).

    Article  CAS  PubMed  Google Scholar 

  71. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  72. Frisch, G. et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol. Dial. Transplant. 20, 2139–2145 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Maes, B. D. et al. Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int. 65, 1842–1849 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Tang, S. C. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 77, 543–549 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  76. Lv, J. et al. Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy. Nephrol. Dial. Transplant. 23, 2868–2872 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Tang, Z. et al. Idiopathic IgA nephropathy with diffuse crescent formation. Am. J. Nephrol. 22, 480–486 (2002).

    Article  PubMed  Google Scholar 

  78. Tumlin, J. A., Lohavichan, V. & Hennigar, R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol. Dial. Transplant. 18, 1321–1329 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Pankhurst, T. et al. Vasculitic IgA nephropathy: prognosis and outcome. Nephron Clin. Pract. 112, c16–c24 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Kim, S. M. et al. Clinicopathologic characteristics of IgA nephropathy with steroid-responsive nephrotic syndrome. J. Korean Med. Sci. 24 (Suppl.) S44–S49 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Lai, K. N., Lai, F. M., Ho, C. P. & Chan, K. W. Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin. Nephrol. 26, 174–180 (1986).

    CAS  PubMed  Google Scholar 

  82. Oh, H. J. et al. Clinical outcomes, when matched at presentation, do not vary between adult-onset Henoch-Schönlein purpura nephritis and IgA nephropathy. Kidney Int. 82, 1304–1312 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Chartapisak, W., Opastirakul, S., Hodson, E. M., Willis, N. S. & Craig, J. C. Interventions for preventing and treating kidney disease in Henoch-Schonlein Purpura (HSP). Cochrane Database of Systematic Reviews, Issue 3. Art No.: CD005128. http://dx.doi.org/10.1002/14651858.CD005128.pub2.

  84. Pillebout, E., Alberti, C., Guillevin, L., Ouslimani, A. & Thervet, E. Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients with severe Henoch Schonlein Purpura. Kidney Int. 78, 495–502 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Floege, J. & Gröne, H. J. Recurrent IgA-nephropathy in the renal allograft: not a benign condition. Nephrol. Dial. Transplant. (in press).

  86. Moroni, G. et al. The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival. Nephrol. Dial. Transplant. http://dx.doi.org/10.1093/ndt/gfs472.

  87. Pham, P. T. & Pham, P. C. The impact of mycophenolate mofetil versus azathioprine as adjunctive therapy to cyclosporine on the rates of renal allograft loss due to glomerular disease recurrence. Nephrol. Dial. Transplant. 27, 2965–2971 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Berthoux, F. et al. Antithymocyte globulin (ATG) induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy. Transplantation 85, 1505–1507 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Clayton, P., McDonald, S. & Chadban, S. Steroids and recurrent IgA nephropathy after kidney transplantation. Am. J. Transplant. 11, 1645–1649 (2011).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Divisions of Nephrology and Immunology, RWTH University of Aachen, Pauwelstrasse 30, Aachen, D-52057, Germany

    Jürgen Floege

  2. The John Walls Renal Unit, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK

    John Feehally

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Correspondence to Jürgen Floege.

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J. Floege declares an association with the following company: Pharmalink (consultant). J. Feehally declares no competing interests.

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Floege, J., Feehally, J. Treatment of IgA nephropathy and Henoch–Schönlein nephritis. Nat Rev Nephrol 9, 320–327 (2013). https://doi.org/10.1038/nrneph.2013.59

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