IgA nephropathy


Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined, but current biochemical and genetic data implicate overproduction of aberrantly glycosylated IgA1. These aberrant immunoglobulins are characterized by galactose deficiency of some hinge-region O-linked glycans. However, aberrant glycosylation alone is insufficient to induce renal injury: the participation of glycan-specific IgA and IgG autoantibodies that recognize the undergalactosylated IgA1 molecule is required. Glomerular deposits of immune complexes containing undergalactosylated IgA1 activate mesangial cells, leading to the local overproduction of cytokines, chemokines and complement. Emerging data indicate that mesangial-derived mediators that are released following mesangial deposition of IgA1 lead to podocyte and tubulointerstitial injury via humoral crosstalk. Patients can present with a range of signs and symptoms, from asymptomatic microscopic haematuria to macroscopic haematuria. The clinical progression varies, with 30–40% of patients reaching end-stage renal disease 20–30 years after the first clinical presentation. Currently, no IgAN-specific therapies are available and patients are managed with the aim of controlling blood pressure and maintaining renal function. However, new therapeutic approaches are being developed, building upon our ever-improving understanding of disease pathogenesis.

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Figure 1: The glomerulus in IgA nephropathy.
Figure 2: Global distribution of patients with IgA nephropathy in some key regions of the world.
Figure 3: Pathogenetic model of IgA nephropathy.
Figure 4: Structure and synthesis of human IgA1 O-glycans.
Figure 5: Pathways leading to glomerular damage, podocyte dysfunction and tubulointerstitial injury in IgA nephropathy.
Figure 6: Renal biopsy findings in a patient with IgA nephropathy.
Figure 7: Different stages of pathology in IgA nephropathy.
Figure 8: An algorithm of proposed treatment options for IgA nephropathy.


  1. 1

    Chailimpamontree, W. et al. Probability, predictors, and prognosis of posttransplantation glomerulonephritis. J. Am. Soc. Nephrol. 20, 843–851 (2009).

  2. 2

    Tam, K. Y. et al. Macromolecular IgA1 taken from patients with familial IgA nephropathy or their asymptomatic relatives have higher reactivity to mesangial cells in vitro. Kidney Int. 75, 1330–1339 (2009).

  3. 3

    Bisceglia, L. et al. Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am. J. Hum. Genet. 79, 1130–1134 (2006).

  4. 4

    Gharavi, A. et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat. Genet. 43, 321–327 (2011).

  5. 5

    Kiryluk, K. et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 8, e1002765 (2012).

  6. 6

    Yu, X. Q. et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat. Genet. 44, 178–182 (2011).

  7. 7

    Woo, K. et al. The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades. Clin. Nephrol. 74, 372–383 (2010).

  8. 8

    Barsoum, R. S. Glomerulonephritis in disadvantaged populations. Clin. Nephrol. 74, S44–S50 (2010).

  9. 9

    Khalifa, E. H., Kaballo, B. G., Suleiman, S. M., Khalil, E. A. & El-Hassan, A. M. Pattern of glomerulonephritis in Sudan: histopathological and immunofluorescence study. Saudi J. Kidney Dis. Transpl. 15, 176–179 (2004).

  10. 10

    Wyatt, R. J. et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region Southeastern United States IgA Nephropathy DATABANK Project. J. Am. Soc. Nephrol. 9, 853–858 (1998).

  11. 11

    Imai, E. et al. Kidney disease screening program in Japan: history, outcome, and perspectives. Clin. J. Am. Soc. Nephrol. 2, 1360–1366 (2007).

  12. 12

    Cho, B. S. et al. A nationwide study of mass urine screening tests on Korean school children and implications for chronic kidney disease management. Clin. Exp. Nephrol. 17, 205–210 (2013).

  13. 13

    Sissons, J. G. et al. Isolated glomerulonephritis with mesangial IgA deposits. Br. Med. J. 3, 611–614 (1975).

  14. 14

    Power, D. A. et al. IgA nephropathy is not a rare disease in the United Kingdom. Nephron 40, 180–184 (1985).

  15. 15

    Manno, C. et al. Desmopressin acetate in percutaneous ultrasound-guided kidney biopsy: a randomized controlled trial. Am. J. Kidney Dis. 57, 850–855 (2011).

  16. 16

    Liu, H. et al. Renal biopsy findings of patients presenting with isolated hematuria: disease associations. Am. J. Nephrol. 36, 377–385 (2012).

  17. 17

    Das, U., Dakshinamurty, K. V. & Prayaga, A. Pattern of biopsy-proven renal disease in a single center of south India: 19 years experience. Indian J. Nephrol. 21, 250–257 (2011).

  18. 18

    McQuarrie, E. P., Mackinnon, B., McNeice, V., Fox, J. G. & Geddes, C. C. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int. 85, 198–203 (2014). This paper highlights the failure to detect IgAN early in regions deprived of good primary health care.

  19. 19

    Kiryluk, K. et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 46, 1187–1196 (2014).

  20. 20

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

  21. 21

    Yokoyama, H. et al. Renal disease in the elderly and the very elderly Japanese: analysis of the Japan Renal Biopsy Registry (J-RBR). Clin. Exp. Nephrol. 16, 903–920 (2012).

  22. 22

    Pontier, P. J. & Patel, T. G. Racial differences in the prevalence and presentation of glomerular disease in adults. Clin. Nephrol. 42, 79–84 (1994).

  23. 23

    Schena, F. P. A retrospective analysis of the natural history of primary IgA nephropathy worldwide. Am. J. Med. 89, 209–215 (1990).

  24. 24

    Shen, P. et al. Clinicopathological characteristics and outcome of adult patients with hematuria and/or proteinuria found during routine examination. Nephron Clin. Pract. 103, c149–c156 (2006).

  25. 25

    Suzuki, H. et al. The pathophysiology of IgA nephropathy. J. Am. Soc. Nephrol. 22, 1795–1803 (2011).

  26. 26

    Glassock, R. J. The pathogenesis of IgA nephropathy. Curr. Opin. Nephrol. Hypertens. 20, 153–160 (2011).

  27. 27

    Mestecky, J. et al. IgA nephropathy: molecular mechanisms of the disease. Annu. Rev. Pathol. 8, 217–240 (2013).

  28. 28

    Lai, K. N. et al. Activation of podocytes by mesangial-derived TNF-α: glomerulo–podocytic communication in IgA nephropathy. Am. J. Physiol. Renal Physiol. 294, F945– F955 (2008). This study explores podocytes in IgAN.

  29. 29

    Kiryluk, K. & Novak, J. The genetics and immunobiology of IgA nephropathy. J. Clin. Invest. 124, 2325–2332 (2014). An in-depth review of the genetics and immunobiology of IgAN.

  30. 30

    Suzuki, H. et al. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J. Clin. Invest. 118, 629–639 (2008).

  31. 31

    Suzuki, H. et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J. Clin. Invest. 119, 1668–1677 (2009). This study revealed the importance of antiglycan IgA immune complexes in the pathogenesis of IgAN.

  32. 32

    Novak, J. et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells. Kidney Int. 67, 504–513 (2005).

  33. 33

    Tomana, M. et al. Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int. 52, 509–516 (1997).

  34. 34

    Allen, A. C., Harper, S. J. & Feehally, J. Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin. Exp. Immunol. 100, 470–474 (1995).

  35. 35

    Mestecky, J. et al. Defective galactosylation and clearance of IgA1 molecules as a possible etiopathogenic factor in IgA nephropathy. Contrib. Nephrol. 104, 172–182 (1993).

  36. 36

    Suzuki, H. et al. Cytokines alter IgA1 O-glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes. J. Biol. Chem. 289, 5330–5339 (2014).

  37. 37

    Ju, T. & Cummings, R. D. A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase. Proc. Natl Acad. Sci. USA 99, 16613–16618 (2002).

  38. 38

    Aryal, R. P., Ju, T. & Cummings, R. D. The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. J. Biol. Chem. 285, 2456–2462 (2010).

  39. 39

    Qin, W. et al. External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol. Dial. Transplant. 23, 1608–1614 (2008).

  40. 40

    Szeto, C. C. & Li, P. K. MicroRNAs in IgA nephropathy. Nat. Rev. Nephrol. 10, 249–256 (2014).

  41. 41

    Tomana, M. et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J. Clin. Invest. 104, 73–81 (1999).

  42. 42

    Berthoux, F. et al. Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy. J. Am. Soc. Nephrol. 23, 1579–1587 (2012).

  43. 43

    Maillard, N. et al. Current understanding of the role of complement in IgA nephropathy. J. Am. Soc. Nephrol. 26, 1503–1512 (2015). This is an excellent review of complement biology in IgAN.

  44. 44

    Leung, J. C., Tsang, A. W., Chan, D. T. & Lai, K. N. Absence of CD89, polymeric immunoglobulin receptor, and asialoglycoprotein receptor on human mesangial cells. J. Am. Soc. Nephrol. 11, 241–249 (2000). This is the first study to conclusively exclude the known IgA receptor as being involved in mesangial binding of IgA in IgAN.

  45. 45

    Moura, I. C. et al. Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. J. Am. Soc. Nephrol. 15, 622–634 (2004).

  46. 46

    Moura, I. C. et al. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J. Exp. Med. 194, 417–425 (2001).

  47. 47

    Launay, P. et al. Fcα receptor (CD89) mediates the development of immunoglobulin A (IgA) nephropathy (Berger's disease). Evidence for pathogenic soluble receptor-Iga complexes in patients and CD89 transgenic mice. J. Exp. Med. 191, 1999–2009 (2000).

  48. 48

    Berthelot, L. et al. Transglutaminase is essential for IgA nephropathy development acting through IgA receptors. J. Exp. Med. 209, 793–806 (2012).

  49. 49

    Vuong, M. T. et al. Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney Int. 78, 12871–12877 (2010).

  50. 50

    Berthelot, L. et al. Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes. Kidney Int. 88, 815–822 (2015).

  51. 51

    Lai, K. N. et al. Polymeric IgA1 from patients with IgA nephropathy upregulates transforming growth factor-β synthesis and signal transduction in human mesangial cells via the renin-angiotensin system. J. Am. Soc. Nephrol. 14, 3127–3137 (2003). This is the first study examining the glomerulo–tubular crosstalk in IgAN.

  52. 52

    Hishiki, T. et al. Podocyte injury predicts prognosis in patients with IgA nephropathy using a small amount of renal biopsy tissue. Kidney Blood Press. Res. 24, 99–104 (2001).

  53. 53

    Lemley, K. V. et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 61, 1475–1485 (2002).

  54. 54

    Asao, R. et al. Relationships between levels of urinary podocalyxin, number of urinary podocytes, and histologic injury in adult patients with IgA nephropathy. Clin. J. Am. Soc. Nephrol. 7, 1385–1393 (2012).

  55. 55

    Kodama, F. et al. Translocation of dendrin to the podocyte nucleus in acute glomerular injury in patients with IgA nephropathy. Nephrol. Dial. Transplant. 28, 1762–1772 (2013).

  56. 56

    Lai, K. N. et al. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol. Dial. Transplant. 24, 62–72 (2009).

  57. 57

    Chan, L. Y., Leung, J. C., Tang, S. C., Choy, C. B. & Lai, K. N. Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy. J. Am. Soc. Nephrol. 16, 2306–2317 (2005).

  58. 58

    Wagner, J., Gehlen, F., Ciechanowicz, A. & Ritz, E. Angiotensin II receptor type 1 gene expression in human glomerulonephritis and diabetes mellitus. J. Am. Soc. Nephrol. 10, 545–551 (1999).

  59. 59

    Julian, B. A. et al. Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N. Engl. J. Med. 312, 202–208 (1985).

  60. 60

    Li, M. et al. Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nat. Commun. 6, 7270 (2015). This is a comprehensive genome-wide association study reporting risk alleles for IgAN in Chinese people.

  61. 61

    Liu, R. et al. Novel genes and variants associated with IgA nephropathy by co-segregating with the disease phenotypes in 10 IgAN families. Gene 571, 43–51 (2015).

  62. 62

    Xu, R. et al. Polymorphism of DEFA in Chinese Han population with IgA nephropathy. Hum. Genet. 133, 1299–1309 (2014).

  63. 63

    Gharavi, A. G. et al. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy. J. Am. Soc. Nephrol. 19, 1008–1014 (2008). This study reports the inherited glycosylation defect in familial and sporadic IgAN.

  64. 64

    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).

  65. 65

    Lai, K. N. et al. An overlapping syndrome of IgA nephropathy and lipoid nephrosis. Am. J. Clin. Pathol. 86, 716–723 (1986).

  66. 66

    Working Group of the International IgA Nephropathy Network and the Renal Pathology Society et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 76, 534–545 (2009).

  67. 67

    Coppo, R. et al. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 86, 828–836 (2014).

  68. 68

    Moldoveanu, Z. et al. Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int. 71, 1148–1154 (2007).

  69. 69

    Stangou, M. et al. Urinary levels of epidermal growth factor, interleukin-6 and monocyte chemoattractant protein-1 may act as predictor markers of renal function outcome in immunoglobulin A nephropathy. Nephrology 14, 613–620 (2009).

  70. 70

    Nishiyama, A. et al. Urinary angiotensinogen reflects the activity of intrarenal renin–angiotensin system in patients with IgA nephropathy. Nephrol. Dial. Transplant. 26, 170–177 (2011).

  71. 71

    Zhang, J. J. et al. Levels of urinary complement factor H in patients with IgA nephropathy are closely associated with disease activity. Scand. J. Immunol. 69, 457–464 (2009).

  72. 72

    Bazzi, C. et al. In crescentic IgA nephropathy, fractional excretion of IgG in combination with nephron loss is the best predictor of progression and responsiveness to immunosuppression. Clin. J. Am. Soc. Nephrol. 4, 929–935 (2009).

  73. 73

    Working Group of the International IgA Nephropathy Network and the Renal Pathology Society et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 76, 546–556 (2009). This paper reports the new Oxford classification on the pathology of IgAN.

  74. 74

    Tumlin, J. A. & Hennigar, R. A. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin. Nephrol. 24, 256–268 (2004).

  75. 75

    Lv, J. et al. Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study. J. Am. Soc. Nephrol. 24, 2118–2125 (2013).

  76. 76

    Roberts, I. S. Pathology of IgA nephropathy. Nat. Rev. Nephrol. 10, 445–454 (2014).

  77. 77

    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).

  78. 78

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

  79. 79

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

  80. 80

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

  81. 81

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

  82. 82

    Cheng, J. et al. ACEI/ARB therapy for IgA nephropathy: a meta analysis of randomised controlled trials. Int. J. Clin. Pract. 63, 880–888 (2009). This meta-analysis examines the therapeutic benefit of RAS blockade in IgAN.

  83. 83

    Reid, S. et al. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst. Rev. 3, CD003962 (2011).

  84. 84

    Radhakrishnan, J. & Cattran, D. C. The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines — application to the individual patient. Kidney Int. 82, 840–856 (2012). This is the KDIGO practice guideline recommended for IgAN.

  85. 85

    Tang, S. C. et al. Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study. Nephrol. Dial. Transplant. 27, 613–618 (2012).

  86. 86

    Szeto, C. C., Kwan, B. C., Chow, K. M., Leung, C. B. & Li, P. K. The safety and short-term efficacy of aliskiren in the treatment of immunoglobulin a nephropathy — a randomized cross-over study. PLoS ONE 8, e62736 (2013).

  87. 87

    De Caterina, R., Endres, S., Kristensen, S. D. & Schmidt, E. B. n-3 fatty acids and renal diseases. Am. J. Kidney Dis. 24, 397–415 (1994).

  88. 88

    Donadio, J. V. et al. A controlled trial of fish oil in IgA nephropathy. N. Engl. J. Med. 331, 1194–1199 (1994).

  89. 89

    Dillon, J. J. Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. J. Am. Soc. Nephrol. 8, 1739–1744 (1997).

  90. 90

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

  91. 91

    Donadio, J. V., Larson, T. S., Bergstralh, E. J. & Grande, J. P. A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. Am. J. Soc. Nephrol. 12, 791–799 (2001).

  92. 92

    Ferraro, P. M., Ferraccioli, G. F., Gambaro, G., Fulignati, P. & Costanzi, S. Combined treatment with renin–angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: a randomized controlled trial. Nephrol. Dial. Transplant. 24, 156–160 (2009).

  93. 93

    Lv, J. et al. Corticosteroid therapy in IgA nephropathy. J. Am. Soc. Nephrol. 23, 1108–1116 (2012).

  94. 94

    Tesar, V. et al. Corticosteroids in IgA nephropathy: a retrospective analysis from the VALIGA study. J. Am. Soc. Nephrol. 26, 2248–2258 (2015).

  95. 95

    Rauen, T. et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N. Engl. J. Med. 373, 2225–2236 (2015). This is the latest clinical trial examining the value of corticosteroid therapy in IgAN.

  96. 96

    de Zeeuw, D. et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 65, 2309–2320 (2004).

  97. 97

    Ruggenenti, P. et al. Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. Am. J. Kidney Dis. 35, 1155–1165 (2000).

  98. 98

    US National Library of Science. Therapeutic Evaluation of Steroids in IgA Nephropathy Global study (TESTING study). ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT01560052 (2012).

  99. 99

    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).

  100. 100

    Mitsuiki, K., Harada, A., Okura, T. & Higaki, J. Histologically advanced IgA nephropathy treated successfully with prednisolone and cyclophosphamide. Clin. Exp. Nephrol. 11, 297–303 (2007).

  101. 101

    Inoue, T. et al. Abnormalities of glycogenes in tonsillar lymphocytes in IgA nephropathy. Adv. Otorhinolaryngol. 72, 71–74 (2011).

  102. 102

    Wang, Y. et al. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol. Dial. Transplant. 26, 1923–1931 (2011).

  103. 103

    Kawamura, T. et al. A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy. Nephrol. Dial. Transplant. 29, 1546–1553 (2014).

  104. 104

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

  105. 105

    Chen, X. et al. A randomized control trial of mycophenolate mofeil treatment in severe IgA nephropathy. Zhonghua Yi Xue Za Zhi 82, 796–801 (2002).

  106. 106

    Tang, S. et al. Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int. 68, 802–812 (2005).

  107. 107

    Liu, X. et al. Treatment of severe IgA nephropathy: mycophenolate mofetil/prednisone compared to cyclophosphamide/prednisone. Int. J. Clin. Pharmacol. Ther. 52, 95–102 (2014).

  108. 108

    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).

  109. 109

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

  110. 110

    Roccatello, D. et al. Long-term effects of methylprednisolone pulses and mycophenolate mofetil in IgA nephropathy patients at risk of progression. J. Nephrol. 25, 198–203 (2012).

  111. 111

    Hogg, R. J. et al. Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy. Am. J. Kidney Dis. 66, 783–791 (2015).

  112. 112

    RAND Health. Medical Outcomes Study: 36-Item Short Form Survey instrument. RAND [online], http://www.rand.org/health/surveys_tools/mos/mos_core_36item_survey.html (2009).

  113. 113

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

  114. 114

    Moriyama, T. et al. Prognosis in IgA Nephropathy: a 30 year analysis of 1,012 patients at a single center. PLoS ONE 9, e91756 (2014).

  115. 115

    Lee, H. et al. Long-term prognosis of clinically early IgA nephropathy is not always favorable. BMC Nephrol. 15, 94–103 (2014).

  116. 116

    Lee, M. J. et al. Clinical implication of crescentic lesions in immunoglobulin A nephropathy. Nephrol. Dial. Transplant. 29, 356–364 (2014).

  117. 117

    Schreiner, G. E. & Maher, J. F. Uremia: Biochemistry, Pathogenesis & Treatment (Thomas, 1961).

  118. 118

    Hampers, C. L., Schupak, E., Lowrie, E. G. & Lazarus, J. M. (eds) Long-term Hemodialysis 2nd edn (Grune and Stratton, 1973).

  119. 119

    Hastings, M. C. et al. Biomarkers in IgA nephropathy: relationship to pathogenetic hits. Expert Opin. Med. Diagn. 7, 615–627 (2013).

  120. 120

    Kiryluk, K. et al. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch–Schonlein purpura nephritis. Kidney Int. 80, 79–87 (2011).

  121. 121

    Serino, G., Sallustio, F., Cox, S. N., Pesce, F. & Schena, F. P. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J. Am. Soc. Nephrol. 23, 814–824 (2012).

  122. 122

    Serino, G. et al. Role of let-7b in the regulation of N-acetylgalactosaminyltransferase 2 in IgA nephropathy. Nephrol. Dial. Transplant. 30, 1132–1139 (2015).

  123. 123

    Serino, G. et al. In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy. Kidney Int. http://dx.doi.org/10.1038/ki.2015.333 (2015). This paper reports an international study validating the use of selective miRNAs as biomarkers in diagnosing IgAN.

  124. 124

    Julian, B. A. et al. Application of proteomic analysis to renal disease in the clinic. Proteomics Clin. Appl. 3, 1023–1028 (2009).

  125. 125

    Mischak, H. et al. Implementation of proteomic biomarkers: making it work. Eur. J. Clin. Invest. 42, 1027–1036 (2012).

  126. 126

    Suzuki, H., Suzuki, Y., Novak, J. & Tomino, Y. Development of animal models of human IgA nephropathy. Drug Discov. Today Dis. Models 11, 5–11 (2014).

  127. 127

    Haghpanah, V. et al. Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer. Tumour Biol. http://dx.doi.org/10.1007/s13277-015-3923-z (2015).

  128. 128

    Isaacs, K. L. & Miller, F. Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran–anti-dextran immune complexes. Am. J. Pathol. 111, 298–306 (1983).

  129. 129

    Leung, J. C., Tang, S. C., Lam, M. F., Chan, T. M. & Lai, K. N. Charge-dependent binding of polymeric IgA1 to human mesangial cells in IgA nephropathy. Kidney Int. 59, 277–285 (2001).

  130. 130

    Leung, J. C., Poon, P. Y. & Lai, K. N. Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy? J. Lab. Clin. Med. 133, 152–160 (1999).

  131. 131

    Smith, A., Molyneux, K., Feehally, J. & Barratt, J. Is sialylation of IgA the agent provocateur of IgA nephropathy? Nephrol. Dial. Transplant. 23, 2176–2178 (2008).

  132. 132

    Smerud, H. K. et al. New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol. Dial. Transplant. 26, 3237–3242 (2011).

  133. 133

    Sugiura, H. et al. Effect of single-dose rituximab on primary glomerular diseases. Nephron Clin. Pract. 117, c98–c105 (2011).

  134. 134

    US National Library of Science. Rituximab in progressive IgA nephropathy. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT00498368?term=NCT00498368&rank=1 (2007).

  135. 135

    Navarra, S. V. et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, Phase 3 trial. Lancet 377, 721–731 (2011).

  136. 136

    US National Library of Science. BRIGHT-SC: blisibimod response in IgA nephropathy following at-home treatment by subcutaneous administration. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02062684?term=NCT02062684&rank=1(2014).

  137. 137

    Kim, M. J. et al. Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients. J. Immunol. 189, 3751–3758 (2012).

  138. 138

    US National Library of Science. Safety and efficacy study of fostamatinib to treat immunoglobin A (IgA) nephropathy. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02112838?term=%22Fostamatinib%22+%22IgA+Nephropathy%22&rank=2 (2014).

  139. 139

    Tang, S. C. & Lai, K. N. The ubiquitin-proteasome pathway and IgA nephropathy: a novel link? Kidney Int. 75, 457–459 (2009).

  140. 140

    US National Library of Science. Pilot study of Velcade® in IgA nephropathy. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT01103778?term=NCT01103778&rank=1 (2010).

  141. 141

    Moura, I. C. et al. The glomerular response to IgA deposition in IgA nephropathy. Semin. Nephrol. 28, 88–95 (2008).

  142. 142

    Diven, S. C. et al. IgA induced activation of human mesangial cells: independent of FcαR1 (CD 89). Kidney Int. 54, 837–847 (1998).

  143. 143

    D'Amico, G. et al. Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients. Medicine (Baltimore) 64, 49–60 (1985). A good review of the clinicopathological features of 374 Italian patients with IgAN.

  144. 144

    Cattran, D. C. et al. The impact of sex in primary glomerulonephritis. Nephrol. Dial. Transplant. 23, 2247–2253 (2008).

  145. 145

    Stratta, P. et al. Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an Italian population. Am. J. Kidney Dis. 33, 1071–1079 (1999).

  146. 146

    Knoop, T. et al. Addition of eGFR and age improves the prognostic absolute renal risk-model in 1,134 Norwegian patients with IgA nephropathy. Am. J. Nephrol. 41, 210–219 (2015).

  147. 147

    Kataoka, H. et al. Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters. Clin. Exp. Nephrol. 16, 706–712 (2012).

  148. 148

    D'Amico, G. Clinical features and natural history in adults with IgA nephropathy. Am. J. Kidney Dis. 12, 353–357 (1988).

  149. 149

    Ibels, L. S. & Györy, A. Z. IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (Baltimore) 73, 79–102 (1994).

  150. 150

    Rafalska, A. et al. Stratifying risk for progression in IgA nephropathy: how to predict the future? Pol. Arch. Med. Wewn. 124, 365–372 (2014).

  151. 151

    Lv, J. et al. Natural history of immunoglobulin A nephropathy and predictive factors of prognosis: a long-term follow up of 204 cases in China. Nephrology (Carlton) 13, 242–246 (2008).

  152. 152

    Fofi, C. et al. IgA nephropathy: multivariate statistical analysis aimed at predicting outcome. J. Nephrol. 14, 280–285 (2001).

  153. 153

    Rekola, S., Bergstrand, A. & Bucht, H. IgA nephropathy: a retrospective evaluation of prognostic indices in 176 patients. Scand. J. Urol. Nephrol. 23, 37–50 (1989).

  154. 154

    To, K. F. et al. Outcome of IgA nephropathy in adults graded by chronic histological lesions. Am. J. Kidney Dis. 35, 392–400 (2000).

  155. 155

    Shi, Y. et al. Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial. Kidney Blood Press. Res. 35, 153–160 (2012).

  156. 156

    Cheng, G. Y. et al. Clinical and prognostic implications of serum uric acid levels on IgA nephropathy: a cohort study of 348 cases with a mean 5-year follow-up. Clin. Nephrol. 80, 40–46 (2013).

  157. 157

    Myllymäki, J. M. et al. Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy. Kidney Int. 71, 343–348 (2007).

  158. 158

    Katafuchi, R. et al. Validation study of Oxford classification of IgA nephropathy: the significance of extracapillary proliferation. Clin. J. Am. Soc. Nephrol. 6, 2806–2813 (2011).

  159. 159

    Ferrario, F., Napodano, P., Rastaldi, M. P. & D'Amico, G. Capillaritis in IgA nephropathy. Contrib. Nephrol. 111, 8–12 (1995).

  160. 160

    Mera, J., Uchida, S. & Nagase, M. Clinicopathologic study on prognostic markers in IgA nephropathy. Nephron 84, 148–157 (2000).

  161. 161

    Shen, P., He, L. & Huang, D. Clinical course and prognostic factors of clinical early IgA nephropathy. Neth. J. Med. 66, 242–247 (2008).

  162. 162

    Sevillano, Á. M. et al. Malignant hypertension: a type of IgA nephropathy manifestation with poor prognosis. Nefrologia 35, 42–49 (2015).

  163. 163

    Xu, L. et al. Podocyte number predicts progression of proteinuria in IgA nephropathy. Mod. Pathol. 23, 1241–1250 (2010).

  164. 164

    Edström Halling, S., Sö derberg, 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).

  165. 165

    Nieuwhof, C., Kruytzer, M., Frederiks, P. & van Breda Vriesman, P. J. Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy. Am. J. Kidney Dis. 31, 962–970 (1998).

  166. 166

    Arroyo, A. H. et al. Predictors of outcome for severe IgA nephropathy in a multi-ethnic U. S. cohort. Clin. Nephrol. 84, 145–155 (2015).

  167. 167

    Yamagat, K. et al. Chronic kidney perspectives in Japan and the importance of urinalysis screening. Clin. Exp. Nephrol. 12, 1–8 (2008).

  168. 168

    Barbour, S. J. et al. Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease. Kidney Int. 84, 2017–2024 (2013).

  169. 169

    Delclaux, C., Jacquot, C., Callard, P. & Kleinknecht, D. Acute reversible renal failure with macroscopic haematuria in IgA nephropathy. Nephrol. Dial. Transplant. 8, 195–199 (1993).

  170. 170

    Bennett, W. M. & Kincaid-Smith, P. Macroscopic hematuria in mesangial IgA nephropathy: correlation with glomerular crescents and renal dysfunction. Kidney Int. 23, 393–400 (1983).

  171. 171

    Boyce, N. W., Holdsworth, S. R., Thomson, N. M. & Atkins, R. C. Clinicopathological associations in mesangial IgA nephropathy. Am. J. Nephrol. 6, 246–252 (1986).

  172. 172

    Feng, C. Y. et al. Persistent asymptomatic isolated hematuria in children: clinical and histopathological features and prognosis. World J. Pediatr. 9, 163–168 (2013).

  173. 173

    Berg, U. B. Long-term follow up of renal function in IgA nephropathy. Arch. Dis. Child 66, 588–592 (1991).

  174. 174

    Yoshikawa, N. et al. Macroscopic hematuria in childhood IgA nephropathy. Clin. Nephrol. 28, 217–221 (1987).

  175. 175

    Bulut, I. K. et al. Outcome results in children with IgA nephropathy: a single center experience. Int. J. Nephrol. Renovasc. Dis. 5, 23–28 (2012).

  176. 176

    Kim, B. S. et al. Natural history and renal pathology in patients with isolated microscopic hematuria. orean J. Intern. Med. 24, 356–361 (2009).

  177. 177

    Ng, W. L. et al. Clinical and histopathological predictors of progressive disease in IgA nephropathy. Pathology 18, 29–34 (1986).

  178. 178

    Le, W. et al. Long-term outcome of IgA nephropathy patients with recurrent macroscopic hematuria. Am. J. Nephrol. 40, 43–50 (2014).

  179. 179

    Frimat, L. et al. IgA nephropathy: prognostic classification of end-stage renal failure. L'Association des Néphrologues de l'Est. Nephrol. Dial. Transplant. 12, 2569–2575 (1997).

  180. 180

    Mustonen, J., Pasternack, A., Helin, H., & Nikkilä, M. Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis. Am. J. Nephrol. 5, 150–157 (1985).

  181. 181

    Lai, K. N. Pathogenesis of IgA nephropathy. Nat. Rev. Nephrol. 8, 275–283 (2012).

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Author information

Introduction (K.N.L.); Epidemiology (F.P.S.); Mechanisms/pathophysiology (J.N., Y.T. and K.N.L.); Diagnosis, screening and prevention (A.B.F., K.N.L. and S.C.W.T.); Management (K.N.L. and S.C.W.T.); Quality of life (R.J.G.); Outlook (K.N.L. and S.C.W.T.); Overview of the Primer (K.N.L.).

Correspondence to Kar Neng Lai.

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Competing interests

S.C.W.T. is the recipient of the ‘Yu Professorship in Nephrology’ at the University of Hong Kong. F.P.S. has been supported by the grant QLG-1CT-2000-00464 from the European Framework Programme and the Schena Foundation, Bari, Italy. J.N. reports his current funding from the NIH, Bethesda, Maryland, USA, a gift from the IgA Nephropathy Foundation of America, and sponsored-research agreements with Pfizer and Anthera. J.N. is also a co-inventor on the US patent application 14/318,082 (assigned to UAB Research Foundation), and is a co-founder of Reliant Glycosciences, LLC. R.J.G. is a consultant for Abbvie, Astellas, Bristol-Myers Squibb, Chemocentryx, Eli Lilly, Mitsubishi, Sanofi-Genzyme, Wolters-Kluwer (UpToDate), Karger (American Journal of Nephrology and Karger Blog) and American Society of Nephrology (NephSAP). R.J.G. holds stock ownership in REATA, Inc. All other authors declare no competing interests.

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Lai, K., Tang, S., Schena, F. et al. IgA nephropathy. Nat Rev Dis Primers 2, 16001 (2016). https://doi.org/10.1038/nrdp.2016.1

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