1. Glomerulopathies –IgA nephropathy IgA nephropathy - Pathogenesis

2. Glomerulopathies –IgA nephropathy IgA nephropathy - Pathogenesis Mesangial IgA  promotes glomerular inflammation  a series of events  …….  can cause end stage renal disease

3. Glomerulopathies –IgA nephropathy

4. IgA nephropathy - Pathogenesis What specific mechanisms influence the deposition of IgA and its initiation of inflammation?

5. Glomerulopathies –IgA nephropathy

6. IgA nephropathy - Pathogenesis tightly T cell controlled processes in health most polymeric IgA is produced in the mucosal immune system is involved in mucosal defense the bone marrow produces monomeric IgA, which reaches the circulation

7. Glomerulopathies –IgA nephropathy

8. IgA nephropathy - Pathogenesis in IgA nephropathy synthesis of polymeric IgA is increased in the bone marrow and decreased in the mucosa

9. Glomerulopathies –IgA nephropathy

11. IgA nephropathy - Pathogenesis Yes it is

12. Glomerulopathies –IgA nephropathy IgA nephropathy - Pathogenesis Why might this happen? This process is very tightly T cell regulated In response to a mucosal antigen, T cells reach the circulation, but will return to the mucosa to synthesize polymeric IgA if they express alpha 4 beta 7, the mucosal homing receptor If on the other hand, a systemic antigen is confronted, T cells will home to the marrow if they express the alpha 4 beta 1 systemic homing receptor

13. Glomerulopathies –IgA nephropathy

15. IgA nephropathy - Pathogenesis in IgA nephropathy - these processes is abnormal there is an exaggeration of systemic homing receptor expression, which would drive T cells not back to the mucosa but towards the marrow  the abnormal site of IgA1 production, which is one of the features of IgA nephropathy

16. Glomerulopathies –IgA nephropathy

17. IgA nephropathy - Pathogenesis in IgA nephropathy - these processes is abnormal but not only there is an exaggeration of systemic homing receptor expression, which would drive T cells not back to the mucosa but towards the marrow  the abnormal site of IgA1 production, which is one of the features of IgA nephropathy structural abnormalities of the IgA molecule itself

18. Glomerulopathies –IgA nephropathy

20. IgA nephropathy - Pathogenesis Abnormal IgA1 molecule promote IgA1 self-aggregation  production of macromolecular IgA1 act as an antigen  production of IgA1-IgG complexes, which could be deposited influence interaction directly with matrix components and particularly with mesangial cells

21. Glomerulopathies –IgA nephropathy

24. IgA nephropathy - a great clinical heterogeneity

25. Glomerulopathies –IgA nephropathy

26. IgA nephropathy is often presenting as recurrent visible hematuria coinciding with mucosal infection which is almost never seen over the age of 40

27. Glomerulopathies –IgA nephropathy

28. IgA nephropathy a few patients will present nephrotic proteinuria

29. Glomerulopathies –IgA nephropathy

30. IgA nephropathy other patients will be picked up because they have an asymptomatic urine abnormality

31. Glomerulopathies –IgA nephropathy

32. IgA nephropathy others will already have advanced kidney disease when they’re first picked up

33. Glomerulopathies –IgA nephropathy

34. “Is this one disease? Is this the same disease we’re picking up at different stages?” Prof J. Feehally Dept of Nephrology Leicester General Hospital Leicester, United Kingdom

35. Glomerulopathies –IgA nephropathy IgA nephropathy in a global view of this disease it’s extremely different in its prevalence

36. Glomerulopathies –IgA nephropathy

37. IgA nephropathy also a very variable prognosis

38. Glomerulopathies –IgA nephropathy

39. IgA nephropathy - prognosis proteinuria, hypertension and GFR at the time of diagnosis predict outcome that’s true for any glomerular disease

40. Glomerulopathies –IgA nephropathy

41. IgA nephropathy – prognosis glomerulosclerosis, interstitial fibrosis, tubular atrophy predict outcome that’s true for any glomerular disease

42. Glomerulopathies –IgA nephropathy

43. IgA nephropathy – prognosis proteinuria you have not just at presentation but during prolonged follow up is a very powerful predictor of outcome !!

44. Glomerulopathies –IgA nephropathy IgA nephropathy – prognosis how much proteinuria you have during follow up combined with mean arterial pressure during follow up are the most powerful predictor of outcome

45. Glomerulopathies –IgA nephropathy

46. IgA nephropathy and Henoch Schonlein Purpura

47. Glomerulopathies –IgA nephropathy

48. IgA nephropathy and Henoch Schonlein Purpura What is IgA nephropathy? characterised by predominant mesangial IgA deposits by immunofluorescence on the renal biopsy there is no clinical nor serological features, which are specific for IgA nephropathies to make the diagnosis, you really need a renal biopsy with appropriate immunofluorescence What is Henoch Schonlein Purpura? a true clinical syndrome characterised by palpable purpura, arthritis, and abdominal pain, and of course, a glomerulonephritis characterised by predominant IgA deposits

49. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura a more accurate definition of H.S.Purpura a small vessel vasculitis with IgA dominant deposits involving skin, gut, and glomeruli associated with arthritis

50. Glomerulopathies –IgA nephropathy

51. IgA nephropathy and Henoch Schonlein Purpura IgA deposits in the mesangium –for sure it is a primary IgA nephropathy or a H.S.Purpura rule out a systemic disease associated with IgA deposits

52. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

53. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

54. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

55. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura a typical picture of IgA deposits characterized by granular mesangial deposits of IgA

56. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura A more aggressive type of IgA nephropathy associated with much more massive immunoglobulin deposits of IgA there is thorough extension of IgA deposits along the capillary walls is usually associated with proliferative lesion and endocapillary proliferation

57. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura C3 is also found in the mesangium generally with a more or less identical pattern than for IgA – generally the intensity is a little bit weaker

58. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura A more aggressive case - massive deposits of C3 in mesangial area, and also extension along the capillary walls

59. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

60. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

61. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura H.S.Purpura is generally a more aggressive type of glomerulonephritis than IgA nephropathy

62. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

63. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

64. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

65. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

66. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

67. Glomerulopathies –IgA nephropathy IgA nephropathy and Henoch Schonlein Purpura

68. Glomerulopathies –IgA nephropathy management recommendations

69. Glomerulopathies –IgA nephropathy management recommendations

70. Glomerulopathies –IgA nephropathy management recommendations There is no specific treatments for this condition

71. Glomerulopathies –IgA nephropathy management recommendations

72. Glomerulopathies –IgA nephropathy management recommendations

73. Glomerulopathies –IgA nephropathy management recommendations

74. Glomerulopathies –IgA nephropathy management recommendations

75. Glomerulopathies –IgA nephropathy management recommendations

76. Glomerulopathies –IgA nephropathy management recommendations

77. Glomerulopathies –IgA nephropathy management recommendations

78. Glomerulopathies –IgA nephropathy

83. Glomerulopathies