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
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Only a fraction of patients with IgA nephropathy require treatment in order to prevent or reduce progressive loss of glomerular filtration rate (GFR)
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Proteinuria, hypertension and any evidence of established renal damage enable a relatively reliable estimation of patient risk
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The 'low-risk' patient with minor urinary abnormalities, normal GFR and normotension requires regular follow-up only
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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
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Several ongoing studies will re-evaluate the role of systemic or enteric corticosteroids in 'intermediate-risk' patients
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The 'high-risk' patient with a rapid loss of GFR may require more aggressive immunosuppression
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References
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).
Kiryluk, K., Novak, J. & Gharavi, A. G. Pathogenesis of immunoglobulin A nephropathy: recent insight from genetic studies. Annu. Rev. Med. 64, 339–356 (2013).
Feehally, J. & Cameron, J. S. IgA nephropathy: progress before and since Berger. Am. J. Kidney Dis. 58, 310–319 (2011).
Pouria, S. & Barratt, J. Secondary IgA nephropathy. Semin. Nephrol. 28, 27–37 (2008).
Rivera, F., Lopez-Gomez, J. M. & Perez-Garcia, R. Clinicopathologic correlations of renal pathology in Spain. Kidney Int. 66, 898–904 (2004).
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).
Suzuki, K. et al. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 63, 2286–2294 (2003).
Yoshikawa, N. et al. Repeat renal biopsy in children with IgA nephropathy. Clin. Nephrol. 33, 160–167 (1990).
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).
Gutierrez, E. et al. Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J. Am. Soc. Nephrol. 23, 1753–1760 (2012).
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).
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).
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).
D'Amico, G. et al. Prognostic indicators in idiopathic IgA mesangial nephropathy. Q. J. Med. 59, 363–378 (1986).
Berthoux, F. et al. Predicting the risk for dialysis or death in IgA nephropathy. J. Am. Soc. Nephrol. 22, 752–761 (2011).
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).
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).
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).
Yamamoto, R. et al. Cigarette smoking and progression of IgA nephropathy. Am. J. Kidney Dis. 56, 313–324 (2010).
Cattran, D. C. et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 76, 534–545 (2009).
Herzenberg, A. M. et al. Validation of the Oxford classification of IgA nephropathy. Kidney Int. 80, 310–317 (2011).
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).
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).
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).
Shima, Y. et al. Validity of the Oxford classification of IgA nephropathy in children. Pediatr. Nephrol. 27, 783–792 (2012).
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).
ERA-EDTA. Advances in the European Validation Study of the Oxford Classification of IgA Nephropathy (VALIGA) [online], (2011).
Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. Suppl. 2, 139–274 (2012).
Vleming, L. J. et al. Histomorphometric correlates of renal failure in IgA nephropathy. Clin. Nephrol. 49, 337–344 (1998).
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).
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).
Lundberg, S. et al. FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. Clin. J. Am. Soc. Nephrol. 7, 727–734 (2012).
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).
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).
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).
Zwirner, J. et al. Activated complement C3: a potentially novel predictor of progressive IgA nephropathy. Kidney Int. 51, 1257–1264 (1997).
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).
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).
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).
Haubitz, M. et al. Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy. Kidney Int. 67, 2313–2320 (2005).
El Karoui, K. et al. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. J. Am. Soc. Nephrol. 23, 137–148 (2012).
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).
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).
Coppo, R. & D'Amico, G. Factors predicting progression of IgA nephropathies. J. Nephrol. 18, 503–512 (2005).
KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. Suppl. 2, 340–414 (2012).
Floege, J. & Eitner, F. Current therapy for IgA nephropathy. J. Am. Soc. Nephrol. 22, 1785–1794 (2011).
Wilmer, W. A. et al. Management of glomerular proteinuria: a commentary. J. Am. Soc. Nephrol. 14, 3217–3232 (2003).
Abboud, H. & Henrich, W. L. Clinical practice. Stage IV chronic kidney disease. N. Engl. J. Med. 362, 56–65 (2010).
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).
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).
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).
Tanaka, H. et al. Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy. Pediatr. Int. 46, 576–579 (2004).
Russo, D. et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am. J. Kidney Dis. 38, 18–25 (2001).
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).
US National Library of Medicine. ClinicalTrials.gov [online], (2012).
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).
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).
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).
Hou, F. F. et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N. Engl. J. Med. 354, 131–140 (2006).
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).
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).
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).
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).
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).
Pozzi, C. et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353, 883–887 (1999).
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).
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).
Eitner, F. & Floege, J. Glomerular disease: ACEIs with or without corticosteroids in IgA nephropathy? Nat. Rev. Nephrol. 6, 252–254 (2010).
Drescher, W., Schlieper, G., Floege, J. & Eitner, F. Steroid-related osteonecrosis—an update. Nephrol. Dial. Transplant. 26, 2728–2731 (2011).
Pozzi, C. et al. Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy. J. Am. Soc. Nephrol. 21, 1783–1790 (2010).
US National Library of Medicine. ClinicalTrials.gov [online], (2012).
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).
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).
Tang, S. C. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 77, 543–549 (2010).
US National Library of Medicine. ClinicalTrials.gov [online], (2012).
Lv, J. et al. Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy. Nephrol. Dial. Transplant. 23, 2868–2872 (2008).
Tang, Z. et al. Idiopathic IgA nephropathy with diffuse crescent formation. Am. J. Nephrol. 22, 480–486 (2002).
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).
Pankhurst, T. et al. Vasculitic IgA nephropathy: prognosis and outcome. Nephron Clin. Pract. 112, c16–c24 (2009).
Kim, S. M. et al. Clinicopathologic characteristics of IgA nephropathy with steroid-responsive nephrotic syndrome. J. Korean Med. Sci. 24 (Suppl.) S44–S49 (2009).
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).
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).
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.
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).
Floege, J. & Gröne, H. J. Recurrent IgA-nephropathy in the renal allograft: not a benign condition. Nephrol. Dial. Transplant. (in press).
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.
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).
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).
Clayton, P., McDonald, S. & Chadban, S. Steroids and recurrent IgA nephropathy after kidney transplantation. Am. J. Transplant. 11, 1645–1649 (2011).
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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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DOI: https://doi.org/10.1038/nrneph.2013.59
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