1. GLOMERULONEPHRITIS: What is New Mohamed Hany Hafez Professor of Medicine & Nephrology Cairo University

2. Basic Structural Patterns of Glomerular Injury

5. MOLECULAR ORGANIZATION

6. Apical Lateral Basal

7. ACTIN & SYNAPTOPODIN

8. Schematic representation of podocyte dysfunction caused by protein overload in chronic nephropathies - A Schieppati and G Remuzzi KI 64:1523, 2003 PODOCYTE DYSFUNCTION

11. Persistent Trend 1(1999) 2 3 4 5

20. WHY VARIABLE RESPONSE TO STEROIDS IN GN?

21. GENOMICS - PROTEOMICS

22. SDS-PAGE (sodium dodecyl sulphate- Polyacrylamide Gel electrophoresis

23. 6 proteins of podocytes alered by steroids (3days incubation)

24. 6 proteins of podocytes alered by steroids (3days incubation)

25. 3 proteins with known role in protecting cell from injury were upregulated quantitativly by western blotting (ciliary neutrophilic factor,aB crystallin,heat Shock Pr.27)

26. 3

30. a-Actinin-4 19q13:Familial FSGS AD NEPHRIN : 19q13.1:The congenital Nephrotic Syndrome AR PODOCIN 1q25-q31:Familial & Sporadic SRNS &FSGS AR

32. X-linked Alport Syndrome COL4A5 INHERITED BASEMENT MEMBRANE DEFECTS (present with proteinuria,Familial FSGS,or Renal Failure) Autosomal Recessive Hereditary Nephritis COL4 A3 COL4A4 Thin Basement Membrane Disease COL4A4

38. 6 cases

44. Prevalence of Dysproteinemias 1 % 0.4 % Fibrillary-ITC 0.1 % 0.4 % 0.2 % MIDD 0.3 % 0.3 % 0.9 % Amyloid (AL) 357051 4689 556 Number USRDS 1999 Vanderbilt 1986-99(Fogo) RushPresbyterian 1989-99(Korbet) Lesion

45. FIBRILLARY GLOMERULOPATHIES Diseases Defined by organized deposits comprised of extracellular, non-branching, elongated microtubules or microfibrils without periodicity and range from 8 to 60 nm in diameter (Stephen Korbet, ASN ,Philad.,Nov.2002) Differential Diagnosis is important because these rare diseases have different therapeutic &Prognostic implications GREAT MIMICKER IN CLINICAL NEPHROLOGY

46. FIBRILS SIZE(nm)

47. ِِ Microtubule By High power Randomly oriented Fibrils 8-10 nm (beta fibrilosis)

48. CONGO RED AMYLOID POSITIVE FIBRILLARY GLOMERULOPATHIES

56. Monoclonal Immunoglobulin Deposition Disease (MIDD) Diagnosis is Made by Immunofluorescence , interesting that it is in the tubules (Kappa light chains mainly,possibly Heavy Chain deposition or Both Light & Heavy)

58. FIBRILLARY –IMMUNOTACTOID GLOMERULOPATHY BY DEFINITION THE FIBRILLARY DEPOSITS DO NOT STAIN WITH CONGO RED OR THIOFLAVIN T (thus distinguishing them from amyloid fibrils), AND ARE OBSERVED IN ABSENCE OF CIRCULATING CRYOGLOBULINS OR PARAPROTEINS (Brady HR,1998)

62. Immunotactoid-Fibrillary FIBRILLARY Fibronectin deposition IMMUNOTACTOID (Ig content+Tactoid Spindle shape body in EM)

66. The Serologic Analysis of Patients with Glomerulonephritis C3 nephritic factor serologic analysis anti-neutrophil cytoplasmic autoantibodies (ANCA) anti-glomerular basement membrane (GBM) autoantibodies immune complex disease markers no extra- renal disease Systemic necrotizing vasculitis Respiratory necrotizing granulomas Asthma and eosinophilia no lung hemorrhage Lung hemorrhage anti- nuclear antibodies anti- pathogen antibodies IgA- fibronectin aggregates Cryo- globulins ANCA- associated crescentic GN Microscopic poly- arteritis Wegener’s granulo- matosis Churg- Strauss syndrome anti-GBM GN Goodpasture's syndrome Lupus GN Postinfectious or peri- infectious GN IgA nephro- pathy Cryoglobu- linemic GN Membrano- proliferative GN ANCA GN anti-GBM GN immune complex GN glomerulonephritis (GN) + + +

76. THANK YOU