This document provides an overview of kidney diseases focusing on glomerular diseases and nephrotic syndrome. It discusses the structure of the kidney and glomerulus. Glomerular diseases are often immunologically mediated involving circulating immune complexes or antibodies reacting within the glomerulus. Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Primary causes include minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. Minimal change disease appears normal by light microscopy but shows diffuse foot process effacement by electron microscopy. Membranous glomerulonephritis involves subepithelial immune deposits along the glo

2. Presented By
Prof. Dr.
Nabil Tadros Mikhail
MBBS, MS Pathol., PhD Pathol.
Prof. of Pathology
Alexandria University - Egypt
Consultant & Chief Pathologist
King Fahad Central Hospital
Gizan - KSA

3. Kidney diseases
Glomerulonephritis , nephritic & nephrotic syndromes

4. The kidney can be divided into
four morphologic components,
1. Glomeruli
2. Tubules
3. Interstitium
4. Blood vessels.

5. Left: General organization of the kidney.
Right: Parts of a juxtamedullary nephron and its collecting duct and tubule

6. 1
2
Portal circulation of the kidney 2 arterial capillaries

10. The small spaces between adjacent processes constitute the filtration slits

12. subendothelium
intramembranous
subepithelium

18. 
Glomerular diseases are often
immunologically mediated

Whereas tubular and interstitium
are more likely caused by
toxic or infectious agents

19. 
Damage to one component almost
always secondarily affect others.
1. Severe damage to glomeruli affect
peritubular blood flow,
2. Tubular destruction, by increasing
intraglomerular pressure may induce
glomerular atrophy.
3. All forms of chronic renal disease will
ultimately destroy all kidney components
and lead to CRF.

20. Endless triangle

21. Glomerular diseases
 Glomerular diseases are a major problem in
nephrology,
 Chronic glomerulonephritis (GN) is one of
the most common cause of CRF in human .

22. Glomerular diseases
Glomerular diseases
Glomerular diseases

23. Glomerular structure

24. Glomerular structure
 The glomerulus consists of a
network of capillaries invested by
epithelium.

25. Structure of glomerular wall


The glomerular capillary wall is the filtering
area
Consists of four basic structure:
1.
2.
3.
4.
Thin layer of fenestrated endothelial cells.
Glomerular basement membrane (GBM):
Visceral epithelium: (podocytes)
Mesangial cells and mesangial matrix:

28. Structure of glomerular wall

1- Thin layer of fenestrated endothelial cells.

2- Glomerular basement membrane (GBM):
It consists of
1. Collagen
2. Laminin
3. Fibronectin
4. Other proteins.

29. Structure of glomerular wall
3- Visceral epithelium: (podocytes)
 It shows a characteristic foot processes
(pedicles) embedded and adherent to GBM.
 These foot processes are
 separated by 20-30 nm filtration slit
 which are bridged by a thin diaphragm
composed of nephrin molecules.

31. Structure of glomerular wall
3- Visceral epithelium: (podocytes)
 Visceral epithelium is critical to maintain
glomerular barrier function.
 It is the cell type that is largely responsible
for synthesis of GBM.

32. Structure of glomerular wall
4- Mesangial cells and mesangial matrix :
 It serve as a support of glomerular tuft.
 These cells is capable for proliferation.
 The whole glomerulus is surrounded by
parietal epithelium, which lines the
bowman’s space (urinary space), the cavity
in which plasma filtrate first collect.

34.  15% of glomerular filtration
through the mesangium,
 85% of glomerular filtration
through the fenestrated epithelium.

35. PAS to highlight basement membranes.
The capillary loops of the glomerulus are well-defined and thin.

36. Glomerular barrier function

The major characteristic of glomerular
filtration are
1. High permeability to water and small
molecules
2. Almost impermeable to molecules of the
size of albumin (70KD).

37. Glomerular barrier function
 The latter characteristic is called
glomerular barrier function,
 Discriminates among protein depending on their size
(the larger, the less permeable).
 Also the charge affect the permeability
(The more cationic the more permeable).

38. Glomerular diseases

39. Glomerular diseases
 Glomerular diseases may be
 Primary ,where the kidney is the main or
the only organ affected.
 Secondary to other disease as
1. SLE,
2. DM,
3. Amyloidosis. ,
4. Polyarteritis nodosa
5. others.

40. Here amyloid deposits are seen in glomeruli at the left and arteries at the right.

41. Amyloidosis may be
 "AL" type in patients with plasma cell
dyscrasias (multiple myeloma) in which the
amyloid is associated with excess
immunoglobulin light chain production,
 "AA" type or "amyloid associated" in which
the cause is often chronic inflammatory
diseases.

42. Pathogenesis of glomerular diseases


Immune mechanisms underlie most cases
of primary glomerular diseases .
It may be
1. Antibody mediated
2. Cell mediated.

43. Pathogenesis of glomerular diseases

1- Antibody mediated glomerular injury:

44. Pathogenesis of glomerular diseases

1- Antibody mediated glomerular injury:

Two forms are recognized:
A- Injury resulting from
deposition of circulating immune complexes. (IC)
 B- Injury by
antibody reacting in situ within the glomerulus

(antiglomerular basement membrane antibodies) & (the Heymann’s model)

47. Immunofluorescence microscopy patterns
Granular
Linear

48. A- Circulating immune complexes

The antigen may be
1. Endogenous as in SLE or
2. Exogenous as acute glomerulonephritis
follow certain
 bacteria (Streptococci) or
 viral (HBV).

49. A- Circulating immune complexes




Antigen antibody complexes
are formed in the circulation
and then trapped in the glomeruli,
where they produce injury
through binding of complement .

50. A- Circulating immune complexes
These IC are seen either by
 Electron microscopy as
dense deposits
Immunofluorescence microscopy, as
granular deposits



51. granular immune deposits

52. Post-streptococcal glomerulonephritis is
immunologically mediated,
The immune deposits are distributed in the
capillary loops in
A granular, bumpy pattern because of the
focal nature of the deposition process
(granular immune deposits)

53. B- nephritis in situ
 The best example is anti glomerular
basement membrane disease.
 In this type antibody are directed against
fixed antigen in the GBM.
 Also can react to planted non-glomerular
antigens interacting with intrinsic
component (Heymann’s model)

54. B- nephritis in situ
 Some times the anti GBM antibodies cross
react with basement membrane of alveoli
resulting in simultaneous lung and kidney
disease (Good Pasture syndrome).
 The antibody can be visualized along GBM
by indirect immunofluorescence microscopy,
giving a characteristic linear pattern.

55.  Antibody to IgG, has a smooth, diffuse,
linear pattern that is characteristic for
glomerular basement membrane antibody
with Goodpasture's syndrome.

56. Clinical findings of good pasture
syndrome
 There is picture of RPGN with haematuria
and may end in renal failure.
 Haemorraghic interstitial pneumonitis with
haemoptysis, dyspnea,..
 Iron ↓ anemia from recurrent hemorrahge.

57. Good Pasture Syndrome
 It is an example of type II hypersensitivity
with cytotoxic antibodies
 Circulating anti GBM antibodies can be
detected in serum (by EIA).
Renal biopsy:
 shows a characteristic
linear immunofluorescence deposits
of IgG and C3.

58. Good Pasture Syndrome
Renal biopsy:
 shows a characteristic
linear immunofluorescence deposits
of IgG and C3.

60. 2- Cell mediated immunity

61. 2- Cell mediated immunity
 There is increasing evidence that sensitized
T cells can cause glomerular injury .
 These may be the case in some forms of
rapidly progressive glomerulonephritis.

62. Mediators of immune injury

Glomerular damage is reflected
physiologically by
 loss of barrier function 
 manifested by proteinuria and 
 reduction of glomerular filtration rate
(GFR).

63. Mediators of immune injury
 Many mechanisms are described:
 Complement-leukocyte mechanism
 C5-9 complement components
 Cytotoxic antibodies
 Monocytes and macrophage.
 Platelets

64. Mediators of immune injury
1- Complement-leukocyte mechanism :
 Activation of complement 
 Generation of chemotactic factors (C5a) 
 Attract neutrophils 
1. Produce Proteases which degrade GBM,
2. O2 free radicals which cause tissue damage
3. Arachidonic acid metabolites (as TXA2) and
which lead to reduction of GFR.

65. Mediators of immune injury

Endothelin & other vasoconstrictors also
contribute to reduction of GFR.

In addition GFR is also ↓ as a result of
obstruction of glomerular lumen by
1. infiltrating inflammatory cells and
2. proliferating mesangial cells.

66. Mediators of immune injury
2- C5-9 complement component:
This component causes epithelial damage.
It also up regulates the transforming growth
factor receptors on epithelial cells , and
 lead to excessive synthesis of extra cellular
matrix and GBM thickening.




67. Mediators of immune injury
 3- Cytotoxic antibodies:
 antibodies directed against glomerular
structure and produce cytotoxicity
(even if IC is absent)

68. Mediators of immune injury
 4- Monocytes and macrophage:
 They secrete a number of biologically active
mediators which contribute to glomerular
damage.
 5- Platelet:
 It aggregates in the glomerulus and release
PG and growth factors.

69. Mediators of immune injury



Epithelial injury:
is the most important factor in glomerular
damage.
This can be induced by
1. Antibody to visceral epithelium or by
2. Toxins or others.

Such injury is reflected
1. Morphologically by loss of foot processes
2. Functionally by proteinuria.

73. Nephrotic syndrome

74. Nephrotic syndrome

Nephrotic syndrome refers to clinical
condition that include five main features;
1.
2.
3.
4.
5.

Massive proteinuria (more than 3.5 gm/day)
Hypo-albuminaemia (less than 3 gm/dl)
Generalized edema
Hyper-lipidaemia (increase cholesterol & triglycerides)
Lipiduria (Lipid casts in urine ).
At the onset renal function is normal (BUN,
creatinine) but later on it is impaired.

75. Pathogenesis of Nephrotic syndrome
 The initial event is damage to capillary wall
 resulting in increase permeability to plasma
protein.
 With long standing heavy proteinuria serum
albumin tend to become depleted and
decreased.
 The drop of osmotic pressure will lead to
generalized edema .

76. Pathogenesis of Nephrotic syndrome

1.
2.
3.
4.

As fluid escape from vessels to tissues,
there is decrease of plasma volume with
compensatory secretion of aldosterone
resulting in salt and water retention and
further aggravate the edema.
Hypo-albuminaemia trigger increased
synthesis of lipids in the liver.

77. Causes of Nephrotic syndrome
Nephrotic syndrome may be
1.Primary or
2.Secondary.

78. Causes of Nephrotic syndrome
 Secondary nephrotic syndrome:
Many disease can lead to Nephrotic
changes in the kidney as
1. DM,
2. SLE,
3. Amyloidosis,
4. Drugs (gold, penicillamine),
5. Infection
(malaria, syphilis, HBV, HIV, ..)

79. Causes of nephrotic syndrome

Primary nephrotic syndrome:
It is encountered in primary glomerular
diseases as :
1.
2.
3.
4.
Lipoid nephrosis (minimal change disease)
Membranous glomerulonephritis
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis

81. 1
Minimal change disease
lipoid nephrosis

82. Minimal change disease
 This disease is also called lipoid nephrosis.
It is the most frequent cause of nephrotic
syndrome in children.
 It is characterized by normal appearance of
glomeruli under light microscope,
 but it show loss of visceral foot processes
when viewed under electron microscope.

83. Lipoid nephrosis
Pathogenesis:
 The current evidence suggest that minimal
change disease results from disorder in T
cells.
 It is postulated that T cells elaborate a factor
that affect nephrin synthesis.

84. Morphology of minimal change disease
Light microscopy
 With light microscopy the glomeruli appear
nearly normal.
 The cells of proximal convoluted tubules
are heavily laden with lipids and this is the
basis of the name lipoid nephrosis.

85. The cells of proximal convoluted tubules are
heavily laden with lipids (lipoid nephrosis).
Slide 21.30

86. Diffuse loss of the foot processes of podocytes
The cells of proximal convoluted tubules are
heavily laden with lipids (lipoid nephrosis).

87. Morphology of minimal change disease
Electron microscopy
 With electron microscopy,
 The only obvious abnormality is the
uniform & diffuse loss of the foot
processes of podocytes

88. This is minimal change disease (MCD)
loss of the epithelial cell (podocyte) foot
processes .

89. Clinical course





Gradual onset of nephrotic syndrome .
It affect only children.
Renal function is preserved in most cases.
Hypertension is absent.
Protein loss is usually confined to small
molecular proteins (selective proteinuria).

90. Prognosis:
 More than 90% of cases respond to
corticosteroids.
 Recurrence may occur and CRF may
develop in less than 5% of cases after
about 25 years

92. 2
Membranous glomerulonephritis
(MGN)

93. Membranous glomerulonephritis
(MGN)
It is a slowly progressive disease
Affect adults between 30-50 years.
It is characterized by the presence of
subepithelial immunoglobulin containing
deposits along the GBM.
 Diffuse thickening of GBM is shown under
light microscopy in well developed cases.




94. Causes of MGN
Primary
 As a primary kidney involvement in
85 % of cases (idiopathic) .
 It results from antibodies that react in situ
to endogenous glomerular antigen.
 The glomerular damage is due to the action
of C5-9 lytic components of complement.

95. Causes of MGN
Secondary:
MGN may occur secondary to
 Many known disorders as
1.
2.
3.
4.

HBV,
Syphilis
Malaria
SLE
Exposure to inorganic salts as
1. Gold
2. Mercury

Exposure to drugs as
1. Penicillamin captopril
2. Non-steroidal anti-inflammatory drugs.

96. Morphology of MGN
 The basic change seen by light microscope
is diffuse thickening of GBM.
 By electron microscopy ,there is
subepithelial deposits along GBM as well as
loss of foot processes.

97. Subepithelial deposits along GBM as well as loss of foot processes.
Diffuse thickening of GBM.

98. Morphology of MGN
 With further progression glomeruli become
sclerosed and hyalinized.
 Immunoflurescence staining of patient
glomerulus show typical granular deposition
of immunoglobulin and complement along
GBM.

99.  Membranous glomerulonephritis in which the capillary loops
are thickened & prominent, but the cellularity is not increased.

100. silver stain of the glomerulus highlights the proteinaceous basement membranes in
black. There are characteristic "spikes" seen with membranous glomerulonephritis
in which the black basement membrane material appears as projections around
the capillary loops.

101. By electron microscopy in membranous glomerulonephritis,
 the darker electron dense immune subepithelial deposits
are seen scattered within the thickened basement membrane.

102. Membranous glomerulonephritis appear
in a diffuse granular pattern by immunofluorescence.

103. Clinical picture of MGN



Gradual onset of nephrotic syndrome.
It affect only adults,
In contrast to lipoid nephrosis,
proteinuria is not selective
(i.e. ↑permeability also to large size proteins as globulins)
 Does not respond to corticosteroids.

104. Clinical picture of MGN
 40% of patients suffer from
progressive disease terminating in
renal failure after 2 - 20 years.
 It is necessary to rule out secondary
causes.

105. Compare lipoid nephrosis A & C with membranous GN B & D

106. (FSG)

107. 3
Focal segmental
glomerulosclerosis
(FSG)

108. Focal segmental glomerulosclerosis
(FSG)

FSG is characterized
histologically by sclerosis affecting
1. Some but not all glomeruli
(focal)
2. Involving only segments of
each glomerulus (segmental).

109. Causes of FSG
Primary or idiopathic:
 FSG account for about 10% of all cases of
nephrotic syndrome.
 It affect both children and adult.
 In children it is important to be differentiated
from minimal change disease.

110. Causes of FSG
 The following aspects are found in FSG only
not found in minimal change disease;
 Hypertension,
 Non-selective proteinuria,
 Haematuria,
 Poor response to corticosteroid.
 Poor prognosis ,
50% develop CRF within 10 years

111. Causes of FSG
 Secondary FSG: occur in
 HIV nephropathy,
 IgA nephropathy ,….

112. Morphology of FSG



The disease affect only some of glomeruli
(focal) initially the juxtamedullary
glomeruli.
It affect only some tufts within the
glomerulus and sparing the others
(segmental).
The lesion exhibit
1. Increased mesangial matrix and
2. Deposition of hyaline masses and lipid droplets.

113. FSG morphology

On electron microscopy ,
1. Visceral epithelium show loss of foot processes as in
lipoid nephrosis and also
2. Greater degree of epithelial detachment

On progression
1. Glomeruli are completely sclerosed (global sclerosis)
2. With tubular atrophy.

114. This is focal segmental glomerulosclerosis (FSGS).
An area of collagenous sclerosis runs across the middle of this glomerulus.

116. 4
Membranoproliferative
glomerulonephritis
(MPGN)

117. Membranoproliferative glomerulonephritis (MPGN)

MPGN is manifested histologically by
1. Alterations of basement membrane & mesangium
2. Proliferation of glomerular cells.


It affect both children and adult.
It account for 10-15 % of cases of
nephrotic syndrome

118. Pathogenesis of MPGN




Two types are recognized.
Most cases of type I MPGN appear to be caused
by circulating IC.
It could be also secondary to SLE, HBV, and other
conditions .
The pathogenesis of type II MPGN is not clear .
It could result from activation of alternative
complement pathway through C3 nephritic factor.

119. Morphology of MPGN
 By light microscope both types of MPGN are
similar.
 The glomeruli are
1. large
2. Proliferation of mesangium,
3. Infiltrating leucocytes
4. lobular appearance.

120. Morphology of MPGN
 The GBM is thickened and show double
contour appearance.
 This splitting of GBM is caused by
mesangial cells inclusion between GBM
laminae.
 It is not easily seen by ordinary
microscope.
 EM or special stain is required.

123. Membranoproliferative glomerulonephritis (MPGN).
Glomerulus has increased overall cellularity, mainly mesangial

124. Morphology of MPGN
 Immunofluorescence and electron
microscopy differentiate between the two
types of MPGN;
 type I MPGN is characterized by
subendothelial deposits(C3 and IgG).
 Type II MPGN is characterized by
intramembranous dense deposits of C3
mainly (dense deposit disease)

125. Subendothelial
deposit
TYPE I
Interposed
mesangial
cell process
Intramembranous
deposit
TYPE II

126. 

A mesangial cell at the lower left that is interposing its cytoplasm at the arrow into the
basement membrane, leading to splitting and reduplication of basement membrane.
This is MPGN type I. These are characteristic subendothelial immune deposits.

127. This EM demonstrates the dense deposits in the basement membrane of MPGN type II.
There are dark electron dense deposits within the basement membrane
that often coalesce to form a ribbon-like mass of deposits

128. Clinical picture of MPGN
 Nephrotic syndrome
is present in 50% of cases.
 40% progress to CRF.
 Type II has a worse prognosis.

129. Clinical picture of MPGN
However MPGN may begin with
 Acute nephritic syndrome
 With haematuria & mild proteinuria
 Others has a combined
nephritic- nephrotic picture.

131. Nephritic Syndrome

132. Nephritic Syndrome

It is a clinical complex usually of acute onset

characterized by five criteria:
1.
2.
3.
4.
5.
Haematuria with diagnostic red cell casts.
Oliguria and impairment of kidney function.
Hypertension.
Mild proteinuria.
Mild edema (localized to face)

133. Pathogenesis
 GFR is decreased due to obstruction of
glomerular lumen by
 The proliferating glomerular cells
 Infiltrating inflammatory cells
 Due to haemodynamic changes
(vasoconstriction).
 The inflammatory reactions injure the
capillary wall and produce hematuria.

134. pathogenesis


Reduced GFR is manifested clinically by oliguria.
Hypertension is the result of both
1. Fluid retention and
2. Renin release from ischemic kidney.

Acute nephritic syndrome may be produced


Secondary to other disorders as SLE or
may as a result of Primary glomerular disease.

135. Kidney Diseases Associated With
Nephritic Syndrome
1. Acute diffuse proliferative post streptococcal
glomerulonephritis The commonest type
2. Rapidly progressive glomerulonephritis
(Crescentic)
3. IgA nephropathy (Berger Disease)
4. Hereditary nephritis
5. Chronic glomerulonephritis

136. Acute diffuse proliferative post
streptococcal glomerulonephritis
(PGN)

137. 1
Acute diffuse proliferative post
streptococcal glomerulonephritis
(PGN)

138. Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)



It is one of the more common glomerular disease
typically caused by Immune complex.
The commonest organism is streptococci,
however it can be caused by
1. Pneumococci.
2. Staphylococci,
3. Viruses as
 Measles
 Mumps.

139. Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)



PGN is an IC disease .
IC are deposited as granular pattern on GBM
there is also blood decrease of complement
(due to increase consumption).

140. Morphology of PGN
Light microscopy
Increased cellularity of glomerular tuft

Affect all glomeruli and hence it is termed diffuse.

This is caused mainly by three cells:
1.
2.
3.
Proliferation and swelling of endothelial cells
Proliferation of mesangial cells
Infiltration by neutrophils and macrophages

141. Morphology of PGN
 In few cases there may be also crescent
inside bowman capsule.
 Electron Microscopy:
 Show immune complex deposits
 Arranged subepithelial along GBM
(called humps)

142. Morphology of PGN
Immuno fluorescence microscopy
 Characteristic granular deposits
of IgG & complement.

143. This glomerulus is hypercellular and capillary loops are poorly defined.

144. 
The hypercellularity of post-streptococcal glomerulonephritis is due to
increased numbers of epithelial, endothelial, and mesangial cells as well as
neutrophils in and around the capillary loops.. (high power)

145.  By electron microscopy, the electron dense immune deposits of poststreptococcal glomerulonephritis are predominantly subepithelial, as
seen here with a large subepithelial "hump" at the right of the
basement membrane (BM).

146. Clinical picture of PGN



History of previous streptococcal infection
2-3 weeks before.
Onset is sudden with fever ,and malaise.
There is picture of nephritic syndrome
1. Oliguria ,
2. Haematuria,
3. Hypertension

147. Laboratory finding of PGN
1- urine :
 Smoky in color,
 Many RBCs are found,
 Diagnostic red cell casts

148. Laboratory finding of PGN

2- Evidence of recent streptococcal
infection:
1. Increased ASOT
2. Anti DNAse


3- Mild elevation of urea and creatinine.
4- Decreased serum complement.

149. Prognosis of PGN
 Recovery occur in most children.
 Few cases develop RPGN.
(Rapidly progressive glomerulonephritis)
 In adult 15-50% develop ESRD
(End stage renal disease) over few years

150. Rapidly progressive
glomerulonephritis
(RPGN)
(Crescentic),

151. 2
Rapidly progressive
glomerulonephritis
(RPGN)
(Crescentic),

152. 2-Rapidly progressive ,(Crescentic), glomerulonephritis (RPGN)

RPGN is characterized by
1. Rapid and progressive loss of renal function
2. Associated with severe oliguria and
3. Death from renal failure within weeks if not treated.

RPGN may be caused by many diseases,
1. Some are Restricted to the kidney
2. Others are systemic.

153. Types of RPGN
Three types are recognized:
Type I
 It is due to anti GBM antibody. The typical
example is good pasture syndrome.
 Diagnosis of this type is important because
the patient improve from treatment by
plasmapheresis which remove pathological
antibodies

154. Types OF RPGN
Type II
 It is an immune complex mediated disorder.
 It can be a complication of any IC nephritis as




post streptococcal GN,
IgA nephropathy,
henoch-schonlien purpura, and SLE.
In some cases the underlying cause is unknown.
 Immunofluorescence studies reveal granular
deposition of IC

155. Types of RPGN




Type III:
It is also called pauci-immune type .
There is no anti GBM or IC by
immunofluorescence or even by EM.
Most of these patients have
Anti Neutrophil Cytoplasmic Antibodies
in serum. (ANCA)
These antibodies play a role in some vasculitis .

156. Types of RPGN


Type III:
This type may be associated with
disorders of systemic vasculitis as
1. PAN
2. wegener granulomatosis.
However in many cases this type is
1. Limited to the kidney &
2. Idiopathic.

157. Morphology of RPGN


Histological picture is characterized by the
presence of crescents in most of the
glomeruli. (Crescentic GN).
Crescents are formed by
1. Proliferation of parietal cells of the bowman capsule
2. Infiltration of mononuclear cells and
3. Deposition of fibrin within bowman space.

158. Morphology of RPGN
 The crescents eventually obliterate
bowman space and compress the glomeruli.
 EM may reveal subepithelial deposits in
some cases

159. Seen here within the glomeruli are crescents composed of proliferating epithelial cells.
Note in the lower left glomerulus that
the capillary loops are markedly thickened
(the so-called "wire loop" lesion of lupus nephritis.

160. Another glomerulus with epithelial crescents
 squashing the glomerular tufts from all sides.

161. 

RPGN may be idiopathic or
may result from
1. SLE,
2. Post-infectious GN
(some cases of post-streptococcal GN),
3. Various types of vasculitis, and
4. Goodpasture's syndrome.

162. This immunofluorescence micrograph of a glomerulus demonstrates
positivity with antibody to fibrinogen.
With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen
leaks into Bowman's space, leading to proliferation of the epithelial cells
and formation of a crescent

163. Clinical picture of RPGN
 Onset is rapid with marked oliguria and
azotemia (Increase urea and creatinine).
 Anuria may occur in some cases (require
dialysis).
 Prognosis is not good, renal failure occur
within weeks if proper treatment in not done
rapidly.

165. 3
IgA nephropathy
(Berger disease)

166. IgA nephropathy (Berger disease)
 It is one of the most common causes of
recurrent gross or microscopic hematuria.
 Pathogenesis:
 Increase IgA concentration is found in more than
50% of cases.
 Patients with IgA nephropathy have increased
production of IgA in bone marrow.
 Also there is abnormalities in IgA clearance.

167. Pathogenesis of IgA nephropathy
 It may be genetic and associated with HLA
types
 It could also be acquired due to increase
IgA synthesis in response to respiratory or
GIT infection.

168. Pathogenesis of IgA nephropathy
 IgA nephropathy occur also in increased
frequency in patients with celiac disease
(intestinal mucosal defect).
 IgA and IgA complexes are then entrapped
in mesangium where they activate
alternative complement pathway and initiate
glomerular injury.

169. Morphology of Berger disease
 The lesions vary considerably.
 The glomeruli may show focal and segmental
mesangial proliferation or diffuse proliferation.
 Immunofluorescence staining show a
characteristic mesangial deposition of IgA often
with C3 and properdin.
 EM demonstrate electron dense deposits in the
mesangium.

170. Slide 21.38

171. This is Berger's disease, or IgA nephropathy.
The IgA is deposited mainly in mesangium, which then
 increases mesangial cellularity as shown at the arrow.

172. This immunofluorescence micrograph demonstrates positivity with antibody to IgA.
Note that the pattern is that of mesangial staining.
This is IgA nephropathy. (Berger Disease)

173. Clinical picture of Berger disease
 The disease often present with gross
hematuria after infection of respiratory tract
or GIT.
 It affects children or young adults
 30-40% has only microscopic hematuria.

174. Clinical picture of Berger disease
 Diagnosis depend on renal biopsy with
immunofluorescence mesangial IgA
deposition.
 It is usually recurrent.
 Many patients maintain normal renal function,
 CRF occur in 25% of cases after many years.

176. 4
Hereditary nephritis

177. Hereditary nephritis
 The most important disease is Alport’s syndrome .
 It is hereditary nephritis associated with nerve
deafness and eye disorders (cataract,…).
 It is due to gene abnormalities which encode
collagen production and so interfere with GBM
structure
 It affect male more frequently between 5-20 years.

178. Hereditary nephritis
 Morphology
 A characteristic foam cells is present due to
accumulation of fat.
 There is glomerular proliferation.

179. Hereditary nephritis
Clinical picture
Patients present with


1.
2.
3.
4.

Haematuria,
Proteinuria
Nerve deafness and
Eye problems.
CRF may develop within years

180. Alport's syndrome
The renal tubular cells appear foamy
because of the accumulation of neutral fats and mucopolysaccharides.
The glomeruli show irregular thickening and splitting of basement membranes

181. Chronic glomerulonephritis
(CGN)

182. 5
Chronic glomerulonephritis
(CGN)

183. Chronic glomerulonephritis (CGN)
 CGN is a most important cause of ESRD
(end stage renal disease) presenting as
CRF.
 It probably represents the end stage of
many disease as RPGN, FSG,MGN and
MPGN.
 However 20% of cases arise with no
history of symptomatic renal disease

184. Slide 21.42

185. Morphology of CGN
 Gross: the kidneys are symmetrically
contracted with diffuse granular surface.
 Microscopically: There is wide spread
replacement of glomerular tuft by avascular
acellular hyaline materials (hyalinization)
with complete glomerular obliteration.
 There is also marked interstitial fibrosis and
tubular atrophy (due to impact on its blood
flow)

186. •Chronic glomerulonephritis
•Complete replacement of glomeruli by
blue stained collagen (Masson trichrome)
Slide 21.43

187. Clinical picture of CGN
 Gradual onset ,usually discovered late in its
course after the onset of renal insufficiency.
 First manifestations include hypertension
,proteinuria ,haematuria, azotemia
 Progression to CRF and death unless renal
dialysis or transplantation is done.

189. Thank you