7. I. PRIMARY GLOMERULONEPHRITIS
• Acute Glomerulonephritis
• Synonyms:
• Acute Diffuse Proliferative GN,
• Diffuse Endocapillary GN
8. Acute Glomerulonephritis
• Acute GN is known to follow acute infection and characteristically
presents as acute nephritic syndrome.
• Based on etiologic agent, acute GN is subdivided into 2 main groups:
• acute post-streptococcal GN & (more common)
• acute non-streptococcal GN
9. ACUTE POST-STREPTOCOCCAL GN (APSGN)
• common form of GN in developing countries,
• mostly affecting children between 2 to 14 years of age but 10% cases
are seen in adults above 40 years of age.
• The onset of disease is generally sudden after 1-2 weeks of
streptococcal infection, most frequently of the throat (e.g. streptococcal
pharyngitis) and sometimes of the skin (e.g. streptococcal impetigo).
10. ACUTE POST-STREPTOCOCCAL GN (APSGN)
ETIOPATHOGENESIS
• The relationship between streptococcal infection and this form of GN is now well establish
• The evidences cited in support are as under:
• i) There is epidemiological evidence of preceding streptococcal sore throat or skin infection
about 1-2 weeks prior to the attack.
• ii) The latent period between streptococcal infection and onset of clinical manifestations of
the disease is compatible with the period required for building up of anti bodies.
• iii) Streptococcal infection may be identified by culture or may be inferred from elevated
titres of antibodies against streptococcal antigens.
• a) anti-streptolysin O (ASO);
• b) anti-deoxyribonuclease B (anti-DNAse B);
• c) anti-streptokinase (ASKase);
• d) anti-nicotinyl adenine dinucleotidase (anti-NADase); and
• e) anti-hyaluronidase (AHase).
• iv) hypocomplementaemia indicating involvement of complement in the glomerular deposits.
• v) identify antigenic component of streptococci which is cytoplasmic antigen, endostreptosin.
11. Acute post-streptococcal GN
Light microscopic appearance. There is increased cellularity due to proliferation of
mesangial cells, endothelial cells and some epithelial cells and infi ltration of the tuft by
neutrophils and monocytes.
12. APSGN - MORPHOLOGIC FEATURES - GROSS
• Grossly, the kidneys are
symmetrically enlarged,
weighing one and a half to
twice the normal weight. Th
e cortical as well as sectio
ned surface show petechial
haemorrhages giving the
characteristic appearance of
fl ea-bitten kidney (Fig
Flea-bitten kidney
The kidney is enlarged in size and
weight.
The cortex shows tiny petechial
haemorrhages visible through
14. ACUTE POST-STREPTOCOCCAL GN
CLINICAL FEATURES
• young child, presenting with acute nephritic syndrome,
• having sudden and abrupt onset following an episode of sore throat or
skin infection
• microscopic or intermittent haematuria,
• red cell casts,
• mild non-selective proteinuria (less than 3 gm per 24 hrs),
• hypertension,
• periorbital oedema
• variably oliguria.
• In adults, the features are atypical and include sudden hypertension,
oedema and azotaemia.
16. RPGN
• RPGN presents with an acute reduction in renal function resulting in
acute renal failure in a few weeks or months.
• It is characterised by formation of ‘crescents’ (crescentic GN) outside the
glomerular capillaries (extracapillary GN)
• RPGN occurs most frequently in adults
• slight male preponderance.
• Prognosis of RPGN in general is dismal.
17. RPGN - ETIOPATHOGENESIS
• A number of primary glomerular and systemic diseases are characterised
by formation of crescents.
• Based on the etiologic agents and pathogenetic mechanism, patients
with RPGN are divided into 3 groups (Table):
• 1. RPGN in systemic diseases (anti-GBM type)
• 2. Post-infectious RPGN (immune-complex type)
• 3. Pauci-immune RPGN.
• Following three serologic markers are used for categorising RPGN:
• i) serum C3 level,
• ii) anti-GBM antibody; and
• iii) anti-neutrophil cytoplasmic antibody (ANCA)
20. RPGN (post-infectious type),
Light microscopic appearance.
There are crescents in Bowman’s space forming adhesions between
the glomerular tuft and Bowman’s capsule.
The tuft shows hypercellularity & leucocytic infiltration.
21. RPGN
diagrammatic representation of ultrastructure of a portion of glomerular
lobule showing epithelial crescent formation & subepithelial granular
deposits.
22. RPGN CLINICAL FEATURES
• Generally, the features of postinfectious RPGN are similar to those of
acute GN, presenting as acute renal failure.
• The patients of Goodpasture’s syndrome may present as acute renal
failure and/or associated intrapulmonary haemorrhage
producing recurrent haemoptysis.
• Prognosis of all forms of RPGN is poor.
• However, post-infectious cases have somewhat better outcome and
may show recovery.
24. Minimal Change Disease
• condition in which the nephrotic syndrome is accompanied by no
apparent change in glomeruli by light microscopy.
• Its other synonyms, lipoid nephrosis and foot process disease,
are descriptive terms for fatty changes in the tubules and electron
microscopic appearance of flattened podocytes respectively.
• Minimal change disease accounts for 80% cases of nephrotic
syndrome in children under 16 years of age with preponderance in
boys (ratio of boys to girls 2:1).
• In fact, historically, lipoid nephrosis was the first condition associated
with nephrotic syndrome.
25. Minimal Change Disease
ETIOPATHOGENESIS
i) Idiopathic (majority of cases).
ii) Cases associated with systemic diseases (Hodgkin’s disease, HIV
infection) & drug therapy (e.g. NSAIDs, rifampicin, interferon- ).
Possible immunologic pathogenesis for MCD:
• i) Absence of deposits by immunofluorescence microscopy.
• ii) Normal circulating levels of complement
• iii) Universal satisfactory response to steroid therapy.
• iv) Evidence of increased suppressor T cell activity with elaboration of
cytokines
• v) Detection of a mutation in nephrin gene
26. Minimal Change Disease
A, Light microscopy shows a normal glomerulus while
B, Diagrammatic representation tubules show cytoplasmic vacuolation and
proteinaceous material. of ultrastructure of a portion of glomerular lobule showing
diffuse fusion or flattening of foot processes of visceral epithelial cells (podocytes).
The GBM is normal and there are no deposits.
27. Minimal-change disease.
A, Glomerulus stained with PAS. Note normal basement membranes and
absence of proliferation.
B, Ultrastructural characteristics of minimal-change disease include
effacement of foot processes (arrows) and absence of deposits. CL, Capillary
lumen; M, mesangium; P, podocyte cell body.
28. Minimal Change Disease
CLINICAL FEATURES
• The classical presentation of MCD is of fully-developed nephrotic
syndrome with massive and highly selective proteinuria;
hypertension is unusual.
• Most frequently, the patients are children under 16 years (peak
incidence at 6-8 years of age).
• The onset may be preceded by an upper respiratory infection, atopic
allergy or immunisation.
• The disease characteristically responds to steroid therapy.
• In spite of remissions and relapses, long-term prognosis is very
good and most children become free of albuminuria after several years.
30. • Membranous nephropathy is characterized by
diffuse thickening of the glomerular capillary wall
due to the accumulation of deposits containing Ig
along the subepithelial side of the basement
membrane.
• uniform, diffuse thickening of the glomerular capillary
wall
32. Membranous
GN
Diagrammatic representation of ultrastructure of a portion of glomerular lobule
showing subepithelial deposits of electron-dense material so that the basement
membrane material protrudes between these deposits.
33. Membranous nephropathy. A, Silver methenamine stain. Note the marked diffuse
thickening of the capillary walls without an increase in the number of cells. There are
prominent “spikes” of silver-staining matrix (arrow) projecting from the basement
membrane lamina densa toward the urinary space, which separate and surround deposited
immune complexes that lack affinity for the silver stain.
B, Electron micrograph showing electron-dense deposits (arrow) along the epithelial side of
the basement membrane (B). Note the effacement of foot processes overlying deposits. CL,
Capillary lumen; End, endothelium; Ep, epithelium; US, urinary space. C
36. Membranous GN
CLINICAL FEATURES
• insidious onset of nephrotic syndrome in an adult.
• The proteinuria is usually of non-selective type.
• microscopic haematuria and hypertension
• Progression to impaired renal function and endstage renal disease with
progressive azotaemia occurs in approximately 50% cases within a span
of 2 to 20 years.
• Renal vein thrombosis (due to hypercoagulability)
• The role and beneficial effects of steroid therapy with or without the
addition of immunosuppressive drugs is debatable