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Post-Infectious Glomerulonephritis

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

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Post-Infectious Glomerulonephritis

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  1. Post-Infectious Glomerulonephritis

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

  3. 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

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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

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

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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. PSGN: Children (Prevention) • Thus, prevention of PSAGN in the developing world continues to be based upon public health measures such as • Improved hygiene and better housing conditions • The elimination of epidemic pyoderma, as occurred in the southern United States over the past 25 years, offers the best hope for control Pediatr Nephrol Epub 23 July 2010

  29. Infection-associated GN (Adults) • Infection-associated GN is rare in adults • Incidence is progressively declining in developed countries • The pattern of the disease has changed over recent decades • Not only Streptococcus but also other bacterial, viral, and parasitic agents have been implicated in the pathogenesis of GN Int Urol Nephrol 2010; 42:477–85.

  30. Infection-associated GN (Adults) (Contd) • In developed countries, GN associated with nonstreptococcal infections is assuming greater importance • This is thought to be secondary to a decline in the incidence of group A streptococcal infections in children and a relative increase in the incidence of GN associated with other infections in adults • Furthermore, an increasing number of adult cases has been observed in alcoholics, patients with diabetes, and intravenous drug abusers Int Urol Nephrol 2010; 42:477–85

  31. Infection-associated GN (Adults) (Contd) • Atypical clinical presentation often issues complex diagnostic challenges and highlights the important diagnostic role of renal biopsy • The more extensive use of renal biopsy has demonstrated the presence of atypical histological features of the disease Int Urol Nephrol 2010; 42:477–85.

  32. Infection-associated GN (Adults) (Contd) • Classically, acute postinfectious GN occurs after streptococcal pharyngitis or skin infection • More recently, other sites of infection and more diverse organisms have been linked to adult infection- associated GN • Studies have demonstrated that Staphylococcus was responsible for an increasing number of cases • MRSA accounted for the majority of cases Int Urol Nephrol 2010; 42:477–85.

  33. Infection-associated GN (Adults) (Contd) • Common sites • Upper respiratory tract • Skin • Lung • Heart/endocarditis and • Teeth Int Urol Nephrol 2010; 42:477–85.

  34. Infection-associated GN (Adults) (Contd) • In studies, • 7–16% of patients had no clinical evidence of infection preceding the renal disease, and • In 24–59% of patients the offending microorganism could not be identified • These data suggests • Infection-associated GN should be included in the differential diagnosis of nephritic/nephrotic syndrome in adults even in the absence of a history of infection Int Urol Nephrol 2010; 42:477–85.

  35. Infection-associated GN (Adults) (Contd) • There is a broad spectrum of glomerular histological findings • The classic glomerular pattern is diffuse endocapillary proliferative GN • Focal mesangial proliferative pattern is also noted in some cases Int Urol Nephrol 2010; 42:477–85.

  36. Infection-associated GN (Adults) (Contd) • 2 histological patterns of GN associated with staphylococcal infection • Diffuse endocapillary and exudative pattern, resembling classic PSGN in patients with S. aureus infection • Pattern identical to membranoproliferative GN in patients with Staphylococcus epidermidis infection secondary to ventriculovascular shunts Int Urol Nephrol 2010; 42:477–85.

  37. Infection-associated GN (Adults) (Contd) • In recent years,a third form of Staphylococcus- associated GN • Mesangial proliferation with IgA-dominant or codominant deposits has been increasingly recognized, which generally occurs in patients with infections caused by MRSA Int Urol Nephrol 2010; 42:477–85.

  38. Postinfectious GN (PIGN): Histology classification • Acute diffuse endocapillary or proliferative GN • Group A streptococcus • Streptococcus viridans • Staphylococcus aureus • Diplococcus pneumoniae • Brucella melitensis • Salmonella typhi • Yersinia enterocolitica • Mycobacterium leprae • Plasmodium falciparum Nephrol Dial Transplant 2001;16(Suppl 6):68–70

  39. Postinfectious GN (PIGN): Histology classification(Contd) • Acute diffuse endocapillary or proliferative GN (contd) • Meninococcus • Mycoplasma • Klebsiella • Measles • Mumps • Varicella • Vaccina • Variola • Cat scrats etc Nephrol Dial Transplant 2001;16(Suppl 6):68–70

  40. Postinfectious GN (PIGN): Histology classification(Contd) • Less commonly, • Diffuse cresentic GN • Streptococcus • Staphylococcus • Legionella • Varicella • Treponema pallidum • Focal cresentic GN • Streptococcus A Nephrol Dial Transplant 2001;16(Suppl 6):68–70

  41. Postinfectious GN (PIGN): Histology classification(Contd) • Rarely, • Mesangiocapillary GN • Streptococcus viridans • Hepatitis C virus • Diffuse/focal mesangial proliferative GN • Diplococcus • Salmonella • Hepatitis B virus • Influenza virus • Adenovirus Nephrol Dial Transplant 2001;16(Suppl 6):68–70

  42. Postinfectious GN (PIGN): Histology classification(Contd) • Rarely, • Focal segmental, necrotizing and sclerosing GN • Bacterial endocarditis • Membranous GN • Syphilis • Hepatitis B virus • Filaria • Schistosoma • Mycobacterium • Plasmodium falciparum • Focal proliferative (Mycoplasma) • Mesangiolytic GN (ECHO) • HUS (Epstein-Barr virus, handavirus) Nephrol Dial Transplant 2001;16(Suppl 6):68–70

  43. Infection-associated GN (Adults) • The prognosis of has not been well defined • But general agreement that the prognosis is less favorable than that of PSGN in children • Complete remission • Before the 1990s: 60–80% of adults • Recent studies found:only 26–56% of adults Int Urol Nephrol 2010; 42:477–85.

  44. Infection-associated GN (Adults) (Contd) • Thus, prognosis of infection-associated GN is worsening in adults • This is probably because typical PSGN has become rarer and the number of patients with severe underlying diseases is progressively increasing Int Urol Nephrol 2010; 42:477–85.

  45. Infection-associated GN (Adults) (Contd) • The prognosis in adults is less favourable, • Especially when accompanied by initial severe impairment in renal function, persistent proteinuria and the nephrotic syndrome • The development of crescents is more common in adults

  46. Conclusions • PSGN • One of the oldest recognized renal disease • Occurs mostly in children • Still a huge burden for underdeveloped countries like India • Treatment remains largely supportive • Hypertension control with salt restriction and diuretics followed by vasodilators

  47. Conclusions (Contd) • PSGN in children (Contd) • Prognosis for recovery is excellent • Vaccines are being developed in developed world • For developing countries • Preventive measures like better hygiene and improved housing conditions are recommended

  48. Conclusions (Contd) • Infection-associated GN in adults • Undergoing change in pattern in recent decades • Nonstreptococcal infections like Staphyloccocus, MRSA are being detected • More common in alcoholics, diabetics, and intravenous drug abusers

  49. Conclusions (Contd) • Infection-associated GN.. (Contd) • Associated with poor prognosis • Complete remission rates ranging 26-56% • Should be included in the differential diagnosis of nephritic/nephrotic syndrome in adults even in the absence of a history of infection (as 24–59% patients organism may not be identified)

  50. Thank You!

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