Acute glomerulonephritis by Dr.Fetiya.pptx

External anatomy ; kidney is bean like structure that lies in the retroperitoneal space slightly above the level of the umbilicus. It is protected by 3 layers of capsules- renal capsule, perinephric fat capsule and renal fascia.
Internal anatomy; Outer layer, the cortex, contains the glomeruli, proximal and distal convoluted tubules, and collecting ducts. Inner layer, the medulla, contains the straight portions of the tubules, the loops of Henle, the vasa recta, and the terminal collecting ducts .
Acute glomerulonephritis is an inflammatory process that involves glomerular tissue that can result in damage to the GBM, mesangium, epithelium or capillary endothelium.
GN generally present as a constellation of findings that includes hematuria (GLOMERULAR) ,HTN ,renal dysfunction ,proteinuria and edema.A clinical course of several forms of glomerulonephritis that have the unifying feature of a histopathologic finding of crescents in the majority of glomeruli .
A sub-group of patients with acute GN designated as “rapidly progressive GN” [RPGN] Which have
An aggressive clinical presentation,
progressive decline of renal function occurring over days to weeks and
presence of crescents around the glomerular tufts in renal biopsy.Patients with systemic vasculitis appear to be particularly prone to develop CGN.
Patients with Henoch-Schönlein purpura (HSP),
Anti neutrophil cytoplasmic antibody (ANCA-mediated GN (microscopic polyangiitis and granulomatosis with poly angiitis), and
systemic lupus erythematosus account for the majority of patients with CGN.Post infectious GN or endocarditis rarely progresses to CGN, but because it is the most common form of GN in childhood it accounts for a significant percentage of patients with CGN in most reports.
If no underlying cause is identified by systemic features, serologic testing, or histologic examination, the disease is classified as idiopathic CGN.Caused by auto antibodies against alveolar and glomurular basement membrane
When there is pulmonary hemorrhage, glomerulonephritis and anti GBM antibody it is referred to as Goodpasture's syndrome.
Causes RPGN.Good pasture disease is rare in childhood.
Hematuria, hypertension and rapid deterioration of RFT
Pulmonary manifestation- cough, SOB, hemoptysis
Iron deficiency anemia for those with prolonged bleeding
Less commonly, patients can have isolated anti-GBM nephritis.Plasmapheresis combined with  high-dose intravenous methylprednisolone  and  cyclophosphamide.
This should be followed by po prednisolone and cyclophosphamide until remission is achieved and then prednisolone/azathioprine for 6-9mos
Duration of therapy
Unknown and depends on remission.There are no randomized controlled trials to indicate the optimal treatment of lupus nephritis in children.
Current therapies are largely based on the histology, clinical severity, and lessons learned from clinical trials of adults with lupus nephritis.
Immunosuppression remains the cornerstone of therapy.

1. Acute Glomerulonephritis Apart From APSGN Presenter -Dr. F etiya M(year II resident) Moderator-Dr. Eyosiyat (assistant professor of pediatrics and child health) 11/12/2015 1

2. Outline Anatomy of kidney , glomerulus Definition and classification of glomerulonephritis Epidemiology of AGN . Presentation and management of specific types of glomerulonephritis Differential diagnostic algorithm of acute glomerulonephritis Summary Recommendation 11/12/2015 2

3. Objective Define , classify and differentiate among different types of glomerulonephritis Know how to approach to a patient with suspected glomerulonephritis Know how to manage acute glomerulonephritis 11/12/2015 3

4. Anatomy of the kidney , glomerulus External anatomy ; kidney is bean like structure that lies in the retroperitoneal space slightly above the level of the umbilicus. It is protected by 3 layers of capsules- renal capsule, perinephric fat capsule and renal fascia. Internal anatomy; Outer layer, the cortex, contains the glomeruli, proximal and distal convoluted tubules, and collecting ducts. Inner layer, the medulla, contains the straight portions of the tubules, the loops of Henle, the vasa recta, and the terminal collecting ducts . 11/12/2015 4

5. Cont.. 11/12/2015 5

6. Cont.. 11/12/2015 6

7. Definition Acute glomerulonephritis is an inflammatory process that involves glomerular tissue that can result in damage to the GBM, mesangium, epithelium or capillary endothelium . GN generally present as a constellation of findings that includes hematuria (GLOMERULAR) ,HTN ,renal dysfunction ,proteinuria and edema. 11/12/2015 7

8. Pathogenesis Glomerular injury may be a result of Genetic disorders, Immunologic disorders, Coagulation disorders or Perfusion disorders. 8 11/12/2015

9. Cont.. Genetic disorders Mutations of genes encoding proteins located within the Glomerulus, interstitium, or tubular epithelium. Most of these defects are within the podocytes . 9 11/12/2015

10. CONT.. Immunologic injury:- Immunologic injury to the glomerulus results in glomerulonephritis, which is a generic term for several diseases, but more precisely a histopathologic term defining inflammation of the glomerular capillaries . 11/12/2015 10

11. Cont.. Two major mechanisms: 1. Deposition of antigen-antibody immune complexes - in situ binding of antibodies to antigens localized within the glomeruli. The antigen can be structural glomeruli components,Alternatively , the antigens may be trapped or deposited within the glomerulus - deposition of circulating antigen antibody immune complexes 2 . Cellular mediated 11/12/2015 11

12. Cont.. Coagulation system Directly after endothelial cell injury or Indirectly after Complement activation Hypo perfusion renal h ypo perfusion causes ATN and collapse of glomerular tuft. 11/12/2015 12

13. Classification of glomerulonephritis Classification of glomerulonephritis is based on Clinical presentation Etiology Histopathology 11/12/2015 13

14. Clinical presentation Acute GN Rapidly progressive GN Recurrent macroscopic hematuria Chronic GN. 11/12/2015 14

15. Etiologic Classification Primary glomerulonephritis Membranoproliferative glomerulonephritis Membranous glomerulonephritis IgA nephropathy Idiopathic crescentic glomerulonephritis APSGN 11/12/2015 15

16. Cont.. Secondary glomerulonephritis Systemic lupus erythematosus nephritis Other post-infectious glomerulonephritis Henoch- Schönlein purpura nephritis Anti-glomerular basement membrane disease Microscopic polyangiitis Wegener granulomatosus 11/12/2015 16

17. Classification based on Histopathology 11/12/2015 17

18. Epidemiology The most common worldwide cause of glomerulonephritis is IGA nephropathy In developing countries ,it rankes 1 st or 2 nd cause of ckd in developed it is 3 rd cause ,over all GN is the second commonest cause of ckd world wide 25%. 11/12/2015 18

19. Cont.. Renal disease pattern among Niger children in 2 hospitals ,renal disease account for 1.6% of all admission ,acute GN Account 1.8%. Renal disease 3.3% admission in black lion ,among them 12.2 % acute glomerulonephritis . 11/12/2015 19

20. Presentation and management of specific types of glomerulonephritis 11/12/2015 20

21. Rapidly progressive GN A clinical course of several forms of glomerulonephritis that have the unifying feature of a histopathologic finding of crescents in the majority of glomeruli . A sub-group of patients with acute GN designated as “rapidly progressive GN” [RPGN] Which have A n aggressive clinical presentation , progressive decline of renal function occurring over days to weeks and presence of crescents around the glomerular tufts in renal biopsy 11/12/2015 21

22. Cont.. 11/12/2015 22

23. Cont.. Patients with systemic vasculitis appear to be particularly prone to develop CGN. Patients with Henoch- Schönlein purpura (HSP), Anti neutrophil cytoplasmic antibody (ANCA-mediated GN (microscopic polyangiitis and granulomatosis with poly angiitis ), and systemic lupus erythematosus account for the majority of patients with CGN 11/12/2015 23

24. Cont.. Post infectious GN or endocarditis rarely progresses to CGN, but because it is the most common form of GN in childhood it accounts for a significant percentage of patients with CGN in most reports. If no underlying cause is identified by systemic features, serologic testing, or histologic examination, the disease is classified as idiopathic CGN. 11/12/2015 24

25. Types of RPGN Based on histological classification Type I: Anti–glomerular basement membrane antibody disease Type II: Immune complex mediated Type III: Pauci -immune (usually antineutrophil cytoplasmic antibody–positive) 11/12/2015 25

26. Clinical Manifestations Most children present with acute nephritis (hematuria, various degrees of renal dysfunction, and hypertension) and usually have concomitant proteinuria, often with nephrotic syndrome. Occasional patients present late in the course of disease with oliguric renal failure 11/12/2015 26

27. Diagnosis The diagnosis of CGN is made by obtaining a kidney biopsy Delineation of the underlying etiology is reached by a combination of additional biopsy findings , extrarenal symptoms and signs, and serologic testing . 11/12/2015 27

28. Prognosis and Treatment progression to end-stage renal disease within weeks to months from the onset is common combination of high-dose corticosteroids and cyclophosphamide may be effective in preventing progressive renal failure in patients with systemic lupus erythematosus, HSP nephritis, granulomatosis with polyangiitis , and IgA nephropathy if given early in the course 11/12/2015 28

29. Cont.. combination with immunosuppression, plasmapheresis has been reported to benefit patients with Goodpasture disease. Plasmapheresis may also benefit patients with ANCA associated CGN, in particular those with the most severe renal dysfunction and pulmonary hemorrhage at presentation 11/12/2015 29

30. Membranoproliferative Glomerulonephritis ( MPGN) MPGN is sometimes called mesangiocapillary glomerulonephritis or lobar glomerulonephritis. most commonly occurs in older children or young adults. 30 11/12/2015

31. Etiologic Classification primary (idiopathic) Secondary forms of glomerular disease. Infection Rheumatologic disease Malignancy Inherited disorder 31 11/12/2015

32. Clinical Manifestations and Evaluation Most common in second decade of life Nephrotic syndrome Acute nephritic syndrome, RPGN Persistent asymptomatic microscopic hematuria and proteinuria Serum C3 complement levels are low in majority of cases 32 11/12/2015

33. Investigation U/A RFT, electrolyte Complement level Test for underlying secondary cause Renal biopsy 11/12/2015 33

34. Cont.. The diagnosis of MPGN is made by renal biopsy. Indications for biopsy include nephrotic syndrome in an older child , significant proteinuria with microscopic hematuria, and hypocomplementemia lasting > 2 mo in a child with acute nephritis 11/12/2015 34

35. Histlogical classification Immunoflourescence based classification Immune complex mediated Complement mediated 35 11/12/2015

36. CONT.. Electron microscope based classification  MPGN I- sub-endothelial deposit MPGN II- dense like deposit along GBM, tubules and bowmans capsule MPGN III- similar to MPGN I but has sub-epithelial deposit. 36 11/12/2015

37. 11/12/2015 37

38. Treatment No defintive therapy exists for MPGN Management has 3 components Treatment of underlying cause Assessing the prognosis of the patient Poor prognosis-Untreated primary MPGN(ESRD 50% by 10yr and 100% by 20yr), 38 11/12/2015

39. Cont.. Those with Nephrotic symptoms , increased creatinine , hypertension, presentation progress to renal failure more rapidly 3. Treatment of glomerulonephritis ACEI, ARB Glucocorticoid Eculizumab (anti–C5 antibody ) Renal transplant. 11/12/2015 39

40. IgA Nephropathy It is the most common chronic glomerulonephritis in children and adolescents with microscopic hematuria(35%) and non nephrotic proteinuria(30%) There is male preponderance commonly in the second and third decade of life 11/12/2015 40

41. Pathogenesis Excessive amount of poorly glycosylated IgA1 in the serum → production of IgG and IgA autoantibodies → immune complex → deposit in the mesangium → mesangeal proliferation The IgA deposit is also accompanied by C3 deposit 11/12/2015 41

42. Pathology Focal and segmental proliferation Epithelial cell crescent formation Glomerular fibrosis and sclerosis Tubulointerstitial fibrosis or sclerosis IgA and C3 complement deposition 11/12/2015 42

43. Clinical features Recurrent gross hematuria Occurs 1-2days after upper respiratory tract or gastrointestinal infections Asymptomatic microscopic hematuria and proteinuria Acute nephritic syndrome is very rare 11/12/2015 43

44. Investigations Serum IgA leve l Serum C3 is normal ASO titer Renal function test Serum protein 11/12/2015 44

45. Cont.. Urine protein to creatinine ratio( Upr:Ucr ) Renal biopsy 11/12/2015 45

46. 11/12/2015 46

47. 11/12/2015 47

48. Cont.. Other treatment modalities Tonsillectomy Long term antibiotics Gluten free diet Fish oil/omega 3 fatty acid preparation (we don't have in Ethiopia) 11/12/2015 48

49. Anti glomerular Basement Membrane Disease ( Anti-GBM Disease) Caused by auto antibodies against alveolar and glomurular basement membrane When there is pulmonary hemorrhage, glomerulonephritis and anti GBM antibody it is referred to as Goodpasture's syndrome. Causes RPGN. 49 11/12/2015

50. Clinical Manifestations Good pasture disease is rare in childhood. Hematuria , hypertension and rapid deterioration of RFT Pulmonary manifestation- cough, SOB, hemoptysis Iron deficiency anemia for those with prolonged bleeding Less commonly, patients can have isolated anti-GBM nephritis 50 11/12/2015

51. Pathology Kidney biopsy shows crescentic glomerulonephritis in most patients. Immunofluorescence microscopy demonstrates the pathognomonic continuous linear deposition of immunoglobulin G along the GBM 11/12/2015 51

52. 11/12/2015 52

53. Treatment Plasmapheresis combined with  high-dose intravenous methylprednisolone  and  cyclophosphamide. This should be followed by po prednisolone and cyclophosphamide until remission is achieved and then prednisolone / azathioprine for 6-9mos Duration of therapy Unknown and depends on remission. 53 11/12/2015

54. Prognosis Untreated, the prognosis of Good pasture disease is poor. Risk of ESRD is above 90% Poor prognosis High cr upon presentation, need for dialysis and crescent formation Patients with isolated nephritis have better prognosis . 11/12/2015 54

55. Lupus Nephritis Common and serious complication of SLE. Although SLE is less frequent in children, renal involvement is more common(80%) and is more severe than that seen in adults. Most important cause of morbidity and mortality in SLE. 55 11/12/2015

56. Pathogenesis Lupus nephritis is primarily due to anti dsDNA Ab Forms immune complexes with DNA, GBM and mesangium , sub endothelial , and/or sub epithelial compartments of the glomerulus This leads to complement activation. 56 11/12/2015

57. Clinical manifestation 11/12/2015 57

58. Histologic classification 11/12/2015 58

59. Diagnosis The diagnosis of SLE is confirmed by the detection of antinuclear antibodies (ANA) and anti-ds DNA ) Low C3 and C4 Renal biopsy Should be performed in all patients with SLE who display even minor urinary abnormalities 11/12/2015 59

60. 11/12/2015 60

61. Treatment There are no randomized controlled trials to indicate the optimal treatment of lupus nephritis in children. Current therapies are largely based on the histology, clinical severity, and lessons learned from clinical trials of adults with lupus nephritis. Immunosuppression remains the cornerstone of therapy. 11/12/2015 61

62. Treatment Therapy is initiated in all patients with prednisone at a dose of 1-2 mg/kg/day in divided doses, followed by a slow steroid taper over 4-6 mo beginning 4-6 wk after serologic remission is achieved For class III and IV Combination of high-dose steroids with either cyclophosphamide or mycophenolate 11/12/2015 62

63. Cont.. For class V lupus nephritis treatment remains unclear. low risk of progression to end-stage renal disease encouraged a less aggressive approach on one hand uncontrolled nephrotic syndrome require more aggressive immunosuppression on the other For Class VI no treatment prevents renal failure 63 11/12/2015

64. Prognosis Overall, renal survival( CKD without the need for end-stage renal disease therapys) is seen in 80% of patients 10 yr after the diagnosis of SLE nephritis. Poor prognostic factors for ESRD diffuse proliferative WHO class IV lupus nephritis , poor renal function at presentation, or persistent nephrotic -range proteinuria . 64 11/12/2015

65. Henoch- Schönlein Purpura ( IgA vasculitis) Is an idiopathic systemic immune complex–mediated vasculitis associated with IgA deposition within small-vessel walls. The most common small vessel vasculitis in children. Peak incidence in early childhood (4-6 yr of age). 90% of cases occur in children. 65 11/12/2015

66. Pathogenesis Similar to IgA nephropathy Mediated by the deposition of polymeric immunoglobulin A (IgA) in glomeruli . IgA immune complexes are deposited throughout the body and activate pathways leading to necrotizing vasculitis .primarily those of the skin and intestine. 66 11/12/2015

67. Clinical Manifestations The classic tetrad of HSP Palpable purpura, Arthralgia, Abdominal pain, and Renal disease . 67 11/12/2015

68. 11/12/2015 68

69. Cont.. Renal manifestation Occurs ~ 50% of patients with HSP. ~ 80% initially microscopic hematuria and proteinuria The remaning present as nephrotic -nephritic syndrome Older children(and adults) have a greater risk for more severe involvement. 69 11/12/2015

70. Investigation CBC- leukocytosis , normal/ thrombocytosis , mild anemia, Elevated ESR and CRP. Stool exam Albumin level 11/12/2015 70

71. Cont.. Urinalysis and serum creatinine Renal biopsy- significant proteinuria, significant hypertension, or elevated serum creatinine. Serum IgA levels have been reported to be elevated in 50 to 70 percent of patients with IgAV 11/12/2015 71

72. 11/12/2015 72

73. Treatment No convincing randomized clinical studies or evidence-based guidelines exist Mild HSP nephritis-does not require treatment, because it usually resolves spontaneously . 11/12/2015 73

74. Cont.. For moderate or severe HSP nephritis high-dose and extended courses of corticosteroids with azathioprine, mycophenolate mofetil, or cyclophosphamide 11/12/2015 74

75. Prognosis and Treatment The prognosis of HSP nephritis for most patients is excellent. Untreated, the risk of developing chronic kidney disease, including ESRD, is 2–5% in all patients with HSP 50% in those with the most severe early renal clinical and histologic features. 75 11/12/2015

76. Differential diagnostic algorithm of acute glomerulonephritis 11/12/2015 76

77. 11/12/2015 77

78. Summary Glomerulonephritis refers to an inflammatory process that involves glomerular tissue. One of the causes significant suffering in children Manifestation, management and prognosis varies according to underlying etiology Renal biopsy is needed to make the diagnosis as well as for prognostic purpose 11/12/2015 78

79. Recommendation Careful evaluation of any patient with clinical renal or urinary sediment abnormality The hospital needs nephrology unit and pediatric nephrologist Necessary investigations should always be available Timely referral of the patient who need nephrologist evaluation 11/12/2015 79

80. Reference's Nelson text book of pediatrics 21 st ed. Uptodate 2023 Comprehensive pediatric nephrology,chapter 11, nephritic syndrome Pattern and outcome of renal disease in hospitalized children in BLH ,Addis Ababa ,Ethiopia, Dr. damte shimels and kebede mola ,2016 11/12 / 2015 80

81. Acute Glomerular Diseases in Children, The Open Urology & Nephrology Journal, Kanwal K. Kher,2015 . Hand book on the manegment of pediatric renal problems in Ethiopia ,march 2009 AGN in children of the Niger delta region , Nigeria , gi mcgil ugwu ,2015 11/12/2015 81

82. THANK YOU 11/12/2015 82