IgA nephropathy - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

About 50% of patients with IgA nephropathy present with recurrent episodes of visible hematuria after an upper respiratory tract infection or gastroenteritis; approximately one third of patients have invisible hematuria and mild proteinuria.
Less than 10% present with either nephrotic syndrome or rapidly progressive glomerulonephritis.
Acute or chronic kidney failure may develop.
Kidney biopsy is required for definitive diagnosis.
Light microscopy shows focal or diffuse mesangial proliferation and extracellular matrix expansion.

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Definition

Epidemiology

Etiology

Pathophysiology

Images

Mesangial hypercellularity in IgA nephropathy (Periodic acid-Schiff stain, x600)
Endocapillary hypercellularity in IgA nephropathy (Periodic acid-Schiff stain, x400)
Segmental glomerulosclerosis in IgA nephropathy (Periodic acid-Schiff stain, x400)
Tubular atrophy and interstitial fibrosis in IgA nephropathy (the atrophied tubules are seen on the left of the field, and normal tubules are seen on the right) (Periodic acid-Schiff stain, x400)
Immunofluorescence staining for IgA showing strong granular staining in the mesangium globally (anti-IgA immunofluorescence, x200)
Electron dense deposits in mesangial and paramesangial regions (electron micrograph, x1000)

Citations

Key Articles

Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013 Jun 20;368(25):2402-14.[Abstract]
Trimarchi H, Barratt J, Cattran DC, et al; 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 May;91(5):1014-21.[Abstract]
Barratt J, Feehally J. Primary IgA nephropathy: new insights into pathogenesis. Semin Nephrol. 2011 Jul;31(4):349-60.[Abstract]
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-S276.[Abstract][Full Text]
Lv J, Zhang H, Wong MG, et al; TESTING Study Group. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA. 2017 Aug 1;318(5):432-42.[Abstract]
Rauen T, Eitner F, Fitzner C, et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36.[Abstract][Full Text]
Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol. 2004 May;24(3):256-68.[Abstract]
Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol. 2004 May;24(3):256-68.[Abstract]

Referenced Articles

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33. Barratt J, Feehally J. Primary IgA nephropathy: new insights into pathogenesis. Semin Nephrol. 2011 Jul;31(4):349-60.[Abstract]
34. Lafayette RA, Kelepouris E. Immunoglobulin A nephropathy: advances in understanding of pathogenesis and treatment. Am J Nephrol. 2018;47 Suppl 1:43-52.[Abstract][Full Text]
35. Yeo SC, Cheung CK, Barratt J. New insights into the pathogenesis of IgA nephropathy. Pediatr Nephrol. 2018 May;33(5):763-77.[Abstract][Full Text]
36. D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. 2000 Aug;36(2):227-37.[Abstract]
37. Galla JH. IgA nephropathy. Kidney Int. 1995 Feb;47(2):377-87.[Abstract]
38. Murugapandian S, Mansour I, Hudeeb M, et al. Epidemiology of glomerular disease in southern Arizona: review of 10-year renal biopsy data. Medicine (Baltimore). 2016 May;95(18):e3633.[Abstract][Full Text]
39. Narva AS. The spectrum of kidney disease in American Indians. Kidney Int Suppl. 2003 Feb;(83):S3-7.[Abstract][Full Text]
40. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-S276.[Abstract][Full Text]
41. Coppo R, D'Amico G. Factors predicting progression of IgA nephropathies. J Nephrol. 2005 Sep-Oct;18(5):503-12.[Abstract]
42. Szeto CC, Lai FM, To KF, et al. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med. 2001 Apr 15;110(6):434-7.[Abstract]
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51. Floege J, Feehally J. Treatment of IgA nephropathy and Henoch-Schönlein nephritis. Nat Rev Nephrol. 2013 Jun;9(6):320-27.[Abstract]
52. Rosselli JL, Thacker SM, Karpinski JP, et al. Treatment of IgA nephropathy: an update. Ann Pharmacother. 2011 Oct;45(10):1284-96.[Abstract]
53. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. 2006 Jun;69(11):1939-44.[Abstract]
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55. Praga M, Gutiérrez E, González E, et al. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol. 2003 Jun;14(6):1578-83.[Abstract]
56. Russo D, Minutolo R, Pisani A, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. 2001 Jul;38(1):18-25.[Abstract]
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59. Pozzi C, Andrulli S, Del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. 2004 Jan;15(1):157-63.[Abstract]
60. Lv J, X, Wang H. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012 Jun;23(6):1108-16.[Abstract]
61. Natale P, Palmer SC, Ruospo M, et al. Immunosuppressive agents for treating IgA nephropathy. Cochrane Database Syst Rev. 2020 Mar 12;3:CD003965.[Abstract][Full Text]
62. Lv J, Zhang H, Wong MG, et al; TESTING Study Group. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA. 2017 Aug 1;318(5):432-42.[Abstract]
63. Hou JH, Le WB, Chen N, et al. Mycophenolate mofetil combined with prednisone versus full-dose prednisone in IgA nephropathy with active proliferative lesions: a randomized controlled trial. Am J Kidney Dis. 2017 Jun;69(6):788-95.[Abstract][Full Text]
64. Xie Y, Chen X, Nishi S, et al. Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy. Kidney Int. 2004 Apr;65(4):1135-44.[Abstract]
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66. Chen Y, Tang Z, Wang Q, et al. Long-term efficacy of tonsillectomy in Chinese patients with IgA nephropathy. Am J Nephrol. 2007;27(2):170-75.[Abstract]
67. Hotta O, Miyazaki M, Furuta T, et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis. 2001 Oct;38(4):736-43.[Abstract]
68. Rauen T, Eitner F, Fitzner C, et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36.[Abstract][Full Text]
69. Liu LL, Wang LN, Liu LL, et al. Omega-3 fatty acids therapy for IgA nephropathy: a meta-analysis of randomized controlled trials. Clin Nephrol. 2012 Feb;77(2):119-25.[Abstract]
70. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. 2006 Jun;69(11):1939-44.[Abstract]
71. Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol. 2004 May;24(3):256-68.[Abstract]
72. Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol. 2002 Jan;13(1):142-8.[Abstract]
73. Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol. 2004 May;24(3):256-68.[Abstract]
74. Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol. 2002 Jan;13(1):142-8.[Abstract]
75. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020 Oct 8;383(15):1436-46.[Abstract][Full Text]
76. Wheeler DC, Toto RD, Stefánsson BV, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021 Jul;100(1):215-24.[Abstract][Full Text]
77. US National Library of Medicine. ClinicalTrials.gov. A multicentre international randomized parallel group double-blind placebo-controlled clinical trial of EMPAgliflozin once daily to assess cardio-renal outcomes in patients with chronic kidney disease. Jan 2022 [internet publication]. [Full Text]
78. Smerud HK, Bárány P, Lindström K, et al. New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant. 2011 Oct;26(10):3237-42.[Abstract][Full Text]
79. Selvaskandan H, Cheung CK, Muto M, et al. New strategies and perspectives on managing IgA nephropathy. Clin Exp Nephrol. 2019 May;23(5):577-88.[Abstract][Full Text]
80. Fellström BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017 May 27;389(10084):2117-27.[Abstract]
81. US National Library of Medicine. ClinicalTrials.gov. A randomized, multicenter, double-blind, parallel-group, active-control study of the efficacy and safety of sparsentan for the treatment of Immunoglobulin A nephropathy. June 2021 [internet publication]. [Full Text]
82. US National Library of Medicine. ClinicalTrials.gov. A phase 3, randomized, double-blind, placebo-controlled study of atrasentan in patients with IgA nephropathy at risk of progressive loss of renal function. Oct 2021 [internet publication].[Full Text]
83. US National Library of Medicine. ClinicalTrials.gov. A randomized, double-blind, placebo-controlled, phase 3 study of the safety and efficacy of OMS721 in patients with Immunoglobulin A (IgA) nephropathy (ARTEMIS - IGAN). May 2019 [internet publication].[Full Text]
84. US National Library of Medicine. ClinicalTrials.gov. A phase 2, randomized, double-blind, placebo-controlled study of cemdisiran in adult patients with IgA nephropathy. Dec 2021 [internet publication].[Full Text]
85. US National Library of Medicine. ClinicalTrials.gov. An open-label phase 2a clinical study to evaluate the effectiveness and safety of IONIS-FB-LRx, an antisense inhibitor of complement factor B, in adult subjects with primary IgA nephropathy. Oct 2021 [internet publication].[Full Text]
86. Gutiérrez E, Carvaca-Fontán F, Luzardo L, et al. A personalized update on IgA nephropathy: a new vision and new future challenges. Nephron. 2020;144(11):555-71.[Abstract][Full Text]
87. US National Library of Medicine. ClinicalTrials.gov. An adaptive seamless randomized, double-blind, placebo-controlled, dose ranging study to investigate the efficacy and safety of LNP023 in primary IgA nephropathy patients. July 2021 [internet publication].[Full Text]
88. US National Library of Medicine. ClinicalTrials.gov. A multi-center, randomized, double-blind, placebo-controlled, parallel group, phase III study to evaluate the efficacy and safety of LNP023 in primary IgA nephropathy patients. Dec 2021 [internet publication]. [Full Text]
89. Harris CL, Pouw RB, Kavanagh D, et al. Developments in anti-complement therapy; from disease to clinical trial. Mol Immunol. 2018 Oct;102:89-119.[Abstract][Full Text]
90. US National Library of Medicine. ClinicalTrials.gov. A phase 1/2, multicenter trial to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BION-1301 in healthy volunteers and adults with IgA nephropathy. Dec 2021 [internet publication].[Full Text]
91. US National Library of Medicine. ClinicalTrials.gov. A multicenter, randomized, double-blind, placebo-controlled, multiple dose study to evaluate the efficacy and safety of VIS649 in participants with Immunoglobulin A (IgA) nephropathy. Sept 2021 [internet publication].[Full Text]
92. Galla JH. IgA nephropathy. Kidney Int. 1995 Feb;47(2):377-87.[Abstract]
93. D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. 2000 Aug;36(2):227-37.[Abstract]
94. Barbour SJ, Coppo R, Zhang H, et al. Evaluating a new international risk-prediction tool in IgA nephropathy. JAMA Intern Med. 2019 Jul 1;179(7):942-52.[Abstract][Full Text]
95. Beerman I, Novak J, Wyatt RJ, et al. The genetics of IgA nephropathy. Nat Clin Pract Nephrol. 2007 Jun;3(6):325-38.[Abstract]
96. Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. 2005 Jul;16(7):2088-97.[Abstract]