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RPGN

RPGN. Dr. Scope. Definition Sign and symptoms Pathogenesis Classification Laboratory approach PSGN Conclusions. Definition: RPGN. Clinical syndrome of glomerular disease Rapid loss of renal function > 50% decline in GFR within 3 mo Nephrotic-nephritic urine sediment

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RPGN

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  1. RPGN Dr.

  2. Scope • Definition • Sign and symptoms • Pathogenesis • Classification • Laboratory approach • PSGN • Conclusions

  3. Definition: RPGN • Clinical syndrome of glomerular disease • Rapid loss of renal function > 50% decline in GFR within 3 mo • Nephrotic-nephritic urine sediment • Extensive crescent formation

  4. Signs & Symptoms • Acute nephritic syndrome eg. hematuria, fluid retention, hypertention, edema, oliguria • Azotemia eg.weakness, nausea and vomiting • 50% - asymptomatic

  5. Pathogenesis Mǿ,T-cell TNF,IL1

  6. Classification Histologically, RPGN is classified on the basis of immunofluorescence findings • Anti-GBM antibody disease • Immune complex disease • Pauci-immune disease

  7. Anti-GBM antibody disease • Goodpasture syndrome • Anti-GBM disease (only kidney involvement) • Pulmonary hemorrhage and hemoptysis due to Ab against the alveolar BM • Linear deposits of IgG (5-20%) • 10-40% may have positive ANCA findings

  8. 2. Immune complex • Granular deposits of Ig in immunofluorescence and electron-dense deposits by electron microscopy • may be perinuclear ANCA (pANCA)–positive without myeloperoxidase (MPO) specificity

  9. 2. Immune complex (cont.) Primary glomerular disease • IgA nephropathy • Membranoproliferative glomerulonephritis • Multisystemic disease • Lupus nephritis • Collagen-vascular disease • Henoch-Schonlein purpura • Post infection • Poststreptococcal GN • Idiopathic

  10. 3. Pauci-Immune • Little or no deposits observed by immunofluorescence or electron microscopy • Wegener granulomatosis (WG) • Churg-Strauss syndrome • Microscopic polyangiitis (MPA) • Renal-limited necrotizing crescentic glomerulonephritis (NCGN) • 80-90% are ANCA-positive.

  11. Laboratory approach ANCA+ve ANCA-ve Normal C3 Low C3 Pauci immune GN Normal C3 Immune complex GN Anti-GBM disease

  12. Further special investigation • C3 • ANCA • ANA • ASO • Anti DNase

  13. Serum C3 normal Low Serum C4 IgA Hereditary disease Low normal APSGN SLE MPGN Shunt nephritis IE Hepatitis B,C Wegener granulomatosis Good pasture’s syndrome Henoch-Schonlein purpura Normal Serum C3 83-177 mg/dL

  14. Further Investigation result • C3 91.27 mg/dL (83-177 mg/dl) • ANCA negative • ANA negative • ASO 63.7 IU/mL • antiDNase B 95.2 U/mL

  15. Serum C3 normal Low Serum C4 IgA Hereditary disease Low normal APSGN SLE MPGN Shunt nephritis IE Hepatitis B,C Wegener granulomatosis Good pasture’s syndrome Henoch-Schonlein purpura Normal Serum C3 83-170 mg/dL

  16. Light microscope: • diffuse endocapillary proliferation • fibrocellular cresent 6/21 glomeruli, normal capillary wall, no tubulointerstitial fibrosis

  17. RPGN:immune complex type

  18. RPGN:immune complex type

  19. Immunofluorescence : • diffuse granular stainning at capillary wall of IgG, C3

  20. RPGN:immune complex type

  21. RPGN:immune complex type

  22. Management • Plasmapheresis, steroids, and cyclophosphamide are used in different combinations depending upon the histological type of RPGN • Prognosis depends upon the etiology and on the extent of glomerular damage already present at the initiation of therapy • Circumferential fibrous crescents involving most of the glomeruli bode a poor outcome

  23. Post-Infectious Glomerulonephritis

  24. Scope • Introduction • PSGN • Epidemiology, Pathogenesis, Morphological features • Children: Clinical features, Treatment, Prognosis, Future, Prevention • Infection-associated GN (Adults) • Conclusions

  25. Introduction • Infectious agents are the most common inciting antigens associated with immune complex mediated glomerulonephritis (GN) • Post-streptococcal GN (PSGN) is the most common form of GN in children • Occurs following a skin or pharyngeal infection with Group A betahemolytic streptococci

  26. Introduction (Contd) • Post-infectious GN has also been associated with other • Bacterial • Viral • Parasitic • Rickettsial • Fungal infections

  27. PSGN: Epidemiology • PSGN is one of the oldest recognized renal diseases • In the past three decades, significant changes have occurred in its epidemiology • Now rare in industrialized nations, but in the underprivileged world, the burden of PSGN ranges between • 9.5 and 28.5 new cases/100,000 individuals/year J Am Soc Nephrol 2008;19: 1855–64.

  28. PSGN: Epidemiology (Contd) • PSGN • Practically disappeared in central Europe, • Where it is now more frequent in the elderly, • Especially in association with debilitating conditions such as • Alcoholism or intravenous drug use J Am Soc Nephrol 2008;19: 1855–64.

  29. PSGN: Epidemiology (Contd) • In India, postinfectious GN represent 73% of the acute glomerulonephridities affecting the elderly, which • May or may not represent a shift in age predominance such as has been referred to previously for Central Europe J Am Soc Nephrol 2008;19: 1855–64.

  30. PSGN: Epidemiology (Contd) • The proportion of cases of acute renal failure that correspond to acute postinfectious GN of demonstrated or assumed poststreptococcal etiology is • 13% in New Delhi • 27% in Bombay • 19.2% in Lucknow • 17.4% in Chandrigarth • 9.3% in Varanasi J Am Soc Nephrol 2008;19: 1855–64.

  31. PSGN: Epidemiology (Contd) • The global incidence of acute PSGN estimated at 472,000 cases per year, • 456,000 of which occurred in less developed countries J Am Soc Nephrol 2008;19: 1855–64.

  32. PSGN: Epidemiology (Contd) J Am Soc Nephrol 2008;19: 1855–64.

  33. PSGN: Epidemiology (Contd) • The annual incidence of PSGN is 9.5 to 28.5 new cases per 100,000 population of all ages in underdeveloped countries J Am Soc Nephrol 2008;19: 1855–64.

  34. PSGN: Pathogenesis • The precise nature of the antigens involved in the formation of the nephritogenic immune complexes is unknown • Streptococcal antigenic substances have been inconsistently detected in glomeruli and circulating immune complexes have been detected in some patients

  35. PSGN: Pathogenesis (Contd) • Since streptococcal antigens do not always cause disease, other mechanisms may be involved, including • Alterations in IgG or glomerular components making them immunogenic • Antigens derived from infectious agents may bind to glomerular structures and induce development of in situ immune complexes

  36. PSGN: Morphologic Features • The glomeruli in post-infectious GN show • Diffuse mesangial proliferation and endocapillary proliferation accompanied by • Infiltration of neutrophils and mononuclear inflammatory cells • Crescents may also be present

  37. PSGN: Morphologic Features (Contd) • Immunofluorescence microscopy • Granular deposits of C3 and IgG along the • Capillary loops and in the • Mesangium • The capillary loop deposits become less frequent after a few weeks, but the mesangial deposits persist for a longer period

  38. PSGN: Morphologic Features (Contd) • Immunofluorescence microscopy (Contd) • Ultrastructurally large subepithelial deposits are present which are usually scattered along the basement membrane • Mesangial deposits are also present

  39. PSGN: Children (Clinical features) • PSGN is primarily a disease of children, 6 to 7 years of age • The onset is usually abrupt, with a latent period of 7 to 21 days between infection and the development of nephritis • During epidemic, the clinical attack rate is 10-12%, but subclinical disease occurs four times more frequently than overt disease

  40. PSGN: Children (Clinical features) (Contd) • Asymptomatic contacts may have hematuria • Common initial clinical manifestations of PSGN are: • Hematuria (Micro or macroscopic) • Edema • Hypertension • Oliguria

  41. PSGN: Children (Clinical features) (Contd) Clinical manifestations—typical course, atypical features Pediatr Nephrol Epub 23 July 2010

  42. PSGN: Children (Clinical features) (Contd) • The acute clinical episode of PSGN is • Usually self-limited and complement levels return to normal within 6 weeks • In most patients hematuria disappears by 6 months but • Proteinuria may persist for two years in a 1/3rd of patients Pediatr Nephrol Epub 23 July 2010

  43. PSGN: Children (Treatment) • Early antimicrobial therapy in affected individuals and family members may prevent the spread of streptococcal infections • Treatment of established infection does not prevent the development of PSGN, but may lessen its severity

  44. PSGN: Children (Treatment) (Contd) • Treatment remains largely supportive and • Usually addresses the most urgent problem of hypertension • No modern studies are available to guide the first choice of antihypertensive agent • However, salt restriction and loop diuretics are the first-line treatment for fluid overload and hypertension; thereafter, hypertensive therapy is often transitioned to vasodilators Pediatr Nephrol Epub 23 July 2010

  45. PSGN: Children (Treatment) (Contd) • Although successful treatment with ACE inhibition has been reported, • ACE inhibitors are generally not used during the acute phase due to the potential for decrease in GFR and hyperkalemia • In those individuals with hypertensive emergencies, • Continuous infusion of anti-hypertensive medication is the preferred initial approach Pediatr Nephrol Epub 23 July 2010

  46. PSGN: Children (Prognosis) • The prognosis for complete recovery is excellent in children, • Even in patients with the nephrotic syndrome or crescentic disease at presentation Pediatr Nephrol Epub 23 July 2010

  47. PSGN: Children (Prognosis) (Contd) • Generally accepted that epidemic cases of PSAGN carry a better prognosis than sporadic cases, with some asserting that healing occurs in all cases • This may be secondary to sporadic cases often presenting in a hospital setting, while • The increased index of suspicion inherent in epidemics leads to the presentation of a greater number of mild cases Pediatr Nephrol Epub 23 July 2010

  48. PSGN: Children (Future) • The availability of a vaccine for group A streptococci is highly desirable and anticipated, • Both in terms of preventing invasive disease and nonsuppurative complications • Current thrust of group A streptococcal vaccine research has been to target M proteins Pediatr Nephrol Epub 23 July 2010

  49. PSGN: Children (Future) (Contd) • Unfortunately, no M proteins from nephritogenic streptococci were included in the vaccine • In addition, because the most common M protein types differ geographically, this vaccine may be of limited efficacy in the developing world, which would presumably continue to bear the majority of the world burden of PSGN and ARF Pediatr Nephrol Epub 23 July 2010

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