This document discusses various glomerular diseases. It begins with definitions of terms like acute renal failure, chronic renal failure, azotemia and uremia. It then describes different types of glomerular diseases like nephritic syndrome, nephrotic syndrome, acute proliferative glomerulonephritis, rapidly progressive glomerulonephritis and their characteristic features. The document contains detailed information on acute post-streptococcal glomerulonephritis including its etiology, morphology, clinical features and prognosis. Histopathological findings and classifications of various glomerular diseases are also summarized.

1. Glomerular diseases
DR. SNEHIL AGRAWAL
1

2. GROSS OF NORMAL KIDNEY
In cross section, this normal
adult kidney demonstrates the
lighter outer cortex and darker
medulla with central pelvis.
2

3. Facts
► Human kidneys are two in number, each weighing about 150 grams
► Filtering more than 170 liters of blood daily to bring out only about 1
liter of concentrated urine.
3

4. 4

5. 5

6. DEFINITIONS
 ACUTE RENAL FAILURE
 CHRONIC RENAL FAILURE
 AZOTEMIA- ELEVATED SERUM LEVELS OF UREA AND
CREATININE WITHOUT ANY CLINICAL SYMPTOMS.
 UREMIA- ELEVATED SERUM LEVELS OF UREA AND
CREATININE WITH CLINICAL SIGNS AND SYMPTOMS DUE
TO METABOLIC AND ENDOCRINE ALTERATIONS. C/F
(organ involvement other than kidney):-
1. Uremic Gastroenteritis
2.Peripheral Neuropathy
3.Uremic Fibrinous Pericarditis.
6

7. Acute Nephritic syndrome
► Acute onset
► Mild to Moderate proteinuria( less than 3.5 g/day)
► Edema
► Azotemia
► Hypertension
► Hematuria
► Etiology (Cause): Acute post streptococcal
Glomerulonephritis
7

8. Nephrotic Syndrome
► Heavy Proteinuria( > 3.5g/day)
► Generalized Edema
► Hypoalbuminemia
► Hyperlipidemia and lipiduria
Cause:
Minimal change disease( in children)
Membranous Nephropathy ( in adult)
Nephrotic Syndrome
causes a bloated
appearance due to
fluid retention
8

9. Proteinuria
► Presence of excess protein in urine
► Example: Nephrotic Syndrome
Hematuria
Blood in Urine
Example: Tumor in Bladder/Kidney,
Few glomerular diseases
9

10. Acute Renal Failure
► Acute loss of renal function
► Oliguria – less urine( < 400ml/day)
► Or, Anuria – No urine flow
► Recent onset azotemia
► Example/ Causes always remember
► 1.Crescentic Glomerulonephritis
► 2.Acute Tubular Necrosis.( ATN)
10

11. Chronic Renal failure
► Prolonged signs and symptoms of Uremia.
► END RESULT OF ALL CHRONIC RENAL DISEASES.
11

12. Proteinuria
Haematuria
SLE
IgA nephropathy
Minimal
change
nephropathy
Membranous
nephropathy
Post-infective
glomerulonephritis
Diabetic
nephropathy
* Adapted from Davidson’s Principles and Practice of Medicine, 20th Edition
Spectrum of glomerular diseases 12

13. HISTOLOGY
4 COMPONENTS
► GLOMERULUS
► TUBULES
► INTERSTITIUM
► BLOOD VESSELS
13

14. Histology of Normal Glomerulus
Glomerular
capillaries
Tubules
RBC
14

15. Glomerular filtration occurs mainly through
fenestrated epithelium.
The normal anionic charge barrier
prevents protein molecules
such as albumin from passing through the
endothelium.
15

16. ‘Nomenclature’
DISEASES OF GLOMERULUS
► Nephritic & Nephrotic syndrome
► Note: Most Common Causes of Renal Failure.
► Note: Diseases mainly immunologically mediated
16

17. Diseases of TUBULES & INTERSTITIUM
► 1. Tubulointerstitial Nephritis
(PYELONEPHRITIS)
► 2.ACUTE TUBULAR NECROSIS
► 3. Drug induced Interstitial Nephritis
17

18. Disease of Blood Vessels
► Benign Nephrosclerosis
► Malignant Nephrosclerosis( seen in Malignant Hypertension)
► Thrombotic Microangiopathy
( Associated With Hemolytic Uremic Syndrome of New
born)
18

19. Cystic Diseases of Kidney
1. Simple cysts
2. Adult Polycystic Kidney Disease
( autosomal dominant)
3. Childhood polycystic kidney disease
( autosomal recessive)
4. Others
19

20. 20

21. 21

22. GBM
Glomerular Capillary Lumen
Bowman’s Capsule Space
+
Lamina rara interna
Lamina densa
Lamina rara externa
Foot Processes
Podocyte
(Visceral epithelium
22

23. 23

24. 24

25. Light microphotograph of
glomerulus
25

26. 26

27. Pathologic Responses of the
Glomerulus to Injury
Hypercellularity
 Characterized by Increase in the
number of cells in the glomerular
tufts.
 This hypercellularity is comprised of
one or more combination of
mesangial or endothelial cell
proliferation, leukocyte infiltration or
formation of crescents.
Basement Membrane Thickening
 On light microscopy appears as thickening
of the capillary walls and is best seen by
PAS staining.
 On electron microscopy it can have one of
the two forms:-
a) Deposition of amorphous electron
dense material on endothelial or epithelial
side of GBM or within the GBM itself.
b) Thickening of the basement membrane
due to increased synthesis of its protein
components as occurs in diabetic
glomerulosclerosis.
27

28. Pathologic Responses of the
Glomerulus to Injury
Hyalinosis
 denotes the accumulation of material that is
homogenous and eosinophilic by light
microscopy.
 By electron microscopy the hyaline is
extracellular ,amorphous made up of leaked
plasma proteins from circulation into
glomerular structures.
 Hyalinosis is a consequence of endothelial or
capillary wall injury.
Sclerosis
 Characterized by accumulation of
extracellular collagenous matrix either
confined to mesengeal areas or involving
the capillary loops or both.
28

29. immune mechanisms underlie most forms of
primary glomerulopathy and many of the secondary
glomerular disorders
29

30. 30

31. 31

32. 32

33. 33

34. HISTOLOGICAL TERMINOLOGIES.
 DIFFUSE: INVOLVE. ALL GLOMERULI.
 FOCAL: PROPORTION OF GLOMERULI.
 GLOBAL: ENTIRE GLOMERULUS.
 SEGMENTAL: A PART OF EACH GLOMERULUS.
 MESANGIAL: INVOLVING THE MESANGIUM.
34

35. Other mechanisms of glomerular injury
a) epithelial cell injury
i) can be induced by Ab to visceral epithelial cell Ag
ii) toxins
iii) cytokines
iv) loss of foot processes
- caused by alterations in nephrin
35

36. 36

37. 37

38. Nephritic syndrome
38

39. Nephritic syndrome
Glomerular diseases presenting with a nephritic syndrome are
often characterized by inflammation in the glomeruli.
The nephritic patient usually presents with
 Hematuria,
 Red cell casts in the urine
 Azotemia,
 Oliguria, and
 Mild to moderate hypertension.
 Proteinuria and edema
39

40. ACUTE PROLIFERATIVE
GLOMERULONEPHRITIS.
 Acute proliferative glomerulonephritis is a group of glomerular
disorders characterized by diffuse proliferation of glomerular
cells and infiltration by leucocytes.
 These are immune complex mediated disorders and the antigens
can be either exogenous or endogenous.
Two types:
Acute post-streptococcal glomerulonephritis.
Acute non- streptococcal glomerulonephritis
40

41. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS.
 Mainly affecting the children of 6-10 years of age group.
 It is an inflammatory but not infective condition that manifests1-4 wks
after post streptococcal infection usually throat or skin infection.
41

42. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS.
ETIOPATHOGENESIS:
 Immunologically mediated disorder.
 Initiated by throat or skin infection caused by
nephritogenic groups. A beta hemolytic streptococci
type 12, 4&1.
 Antibodies are formed against streptococcal antigen
consequently there is formation of immune complex in
the circulation.
 These circulating immune complex are trapped within
glomeruli, deposited on the GBM and initiates the
inflammatory response that induce glomerular damage.
42

43. ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS.
MORPHOLOGY:
Gross:
 Both kidneys are involved and are symmetrically
enlarged.
 Cortical surface shows pinpoint hemorrhages that are
called as” flea bitten kidney”.
43

44. ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS
Light microscopy:
Glomeruli:
 There is diffuse involvement of all the glomeruli.
 Glomeruli are enlarged and hypercellular.
 There is proliferation of endothelial, mesangial and
epithelial cells.
 Infiltration by neutrophils and monocytes are seen in the glomeruli.
Tubules: contain RBC cast.
Interstitium: shows edema, WBC infiltration.
Vessels: Largely unaffected.
44

45. Diffuse Endocapillary Proliferative GN
 Proliferation of endothelial
and mesangial cells
 Cell Swelling
 Inflammatory cells (PMNL)
 Obstruction ofcapillary
lumina
 Enlarged hypercellular
glomeruli.
45

46. APGN- HYPERCELLULARITY 46

47. ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS
Flea bitten kidney:
 Multiple pinpoint hemorrhages on the cortical surface of the
kidney due to congested glomerulus.
 Also seen in malignant nephrosclerosis, HUS and TTP.
Electron microscopy:
 Electron dense deposits on the epithelial aspect are seen that
are called as” humps.”
Immunoflourescence.
 Immune deposits are seen along GBM that are composed of
IgG, IgM and C3.
47

48. ACUTE POST-STREPTOCOCCAL
GLOMERULONEPHRITIS
48

49. 49

50. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS
Lab findings.
 Elevated ASO titer.
 Decreased serum complement levels: C3.
 Elevated blood urea and creatinine levels.
50

51. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS
Urinary findings.
Gross:-
 Oliguria.
 Red or smoky urine due the presence of RBCs and
proteins.
Chemicals:
 protein: Increased.<3Gm/Day.
 Blood is present
Microscopy:
 Presence of RBCs and RBC casts.
51

52. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS
Clinical features:
 Patient is usually is a young child
 Present with sudden onset with features of acute
nephritis and fever, malaise and nausea with a history
of soar throat or skin infection 1-4 wks earlier to the
renal manifestation.
52

53. ACUTE POST STREPTOCOCCAL
GLOMERULONEPHRITIS
Prognosis:
 95% cases show complete recovery with treatment.
 Less than 1% patients show no recovery and progress
to RPGN with clinical features of acute renal failure
and rest of them gradually progress to CGN.
 Adult carry bad prognosis than children with less
than 60% recovery.
53

54. ACUTE NON STREPTOCOCCAL
GLOMERULONEPHRITIS
 Type of acute proliferative glomerulonephritis caused by
other than group A beta hemolytic streptococci.
Agents:
Bacterial:
 Staphylococci, Pneumococci, Meningococci
Viral :
 HBV, HCV, EBV, Mumps, HIV
Parasites:
 Malaria, Toxoplasomosis
54

55. ACUTE NON STREPTOCOCCAL
GLOMERULONEPHRITIS
Morphology:
 Light microscopy, electron microscopy and
immunoflourescence studies are similar to acute
post-streptococcal glomerulonephritis.
 Prognosis is bad compared to acute post-
streptococcal glomerulonephritis
55

56. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
(CRESCENTIC GLOMERULONEPHRITIS)
 In this condition there is severe glomerular injury
and patients presenting with rapid and progressive
loss of renal function leading to oliguria, ARF and if
untreated death.
 There is formation of epithelial crescents in the
glomeruli so it is called as crescentic
glomerulonephritis.
56

57. Classification and Pathogenesis.
TYPE I (ANTI-GBM ANTIBODY)
 Renal limited
 Goodpasture syndrome
TYPE II (IMMUNE COMPLEX)
 Idiopathic
 Post-infectious glomerulonephritis
 Lupus nephritis
 Henoch-Schönlein purpura (IgA nephropathy)
 Others
TYPE III (PAUCI-IMMUNE)
 ANCA-associated
 Idiopathic
 Wegener granulomatosis
 Microscopic polyangiitis
57

58. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
 The first type of RPGN is anti-GBM antibody–induced disease,
 characterized by linear deposits of IgG and, in many cases, C3 in the
GBM that are visualized by immunofluorescence.
 In some of these patients, the anti-GBM antibodies cross-react with
pulmonary alveolar basement membranes to produce the clinical
picture of pulmonary hemorrhage associated with renal failure
(Goodpasture syndrome).
 The Goodpasture antigen is a peptide within the noncollagenous
portion of the α3 chain of collagen type IV.
58

59. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
 The second type of RPGN is the result of immune complex
deposition.
 It can be a complication of any of the immune complex
nephritides, including postinfectious glomerulonephritis,
lupus nephritis, IgA nephropathy, and Henoch Schönlein
purpura.
 Immunofluorescence studies reveal the granular pattern of
staining characteristic of immune complex deposition.
 This type of RPGN frequently demonstrates cellular
proliferation within the glomerular tuft, in addition to
crescent formation.
59

60. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
 The third type of RPGN, also called pauci-immune type, is defined by
the lack of anti-GBM antibodies or immune complexes by
immunofluorescence and electron microscopy.
 Most patients with this type of RPGN have circulating antineutrophil
cytoplasmic antibodies (ANCAs) that produce cytoplasmic (c) or
perinuclear (p) staining patterns ,play a role in some vasculitides.
 Hence, in some cases this type of RPGN is a component of a
systemic vasculitis such as Wegener granulomatosis or microscopic
polyangiitis.
 In many cases pauci-immune crescentic glomerulonephritis is
isolated and hence idiopathic. More than 90% of such idiopathic
cases have c-ANCAs or p-ANCAs in the sera
60

61. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
Morphology :
Gross:
 Both kidneys are involved that are enlarged, pale and
petechial hemorrhages on the cortical surface.
61

62. 62

63. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
Light microscopy:
Crescents
 Crescents are formed by proliferation of parietal cells
and by migration of monocytes and macrophages into
the urinary space. Neutrophils and lymphocytes may be
present.
 The crescents eventually obliterate Bowman space and
compress the glomerular tuft.
 Fibrin strands are frequently prominent between the
cellular layers in the crescents
63

64. Crescentic glomerulonephritis (PAS stain). Note the collapsed glomerular tufts
and the crescent-shaped mass of proliferating parietal epithelial cells and
leukocytes internal to Bowman capsule.
64

65. RAPIDLY PROGRESSIVE G.N.
(CRESCENTIC G.N.)
EM/IF:
 Vary according to the cause.
 Immune complex–mediated cases show granular immune deposits
 Goodpasture syndrome cases show linear GBM fluorescence for Ig and complement,
 Pauci-immune cases have little or no deposition of immune reactants.
Electron microscopy
 Deposits in those cases due to immune complex deposition (type II).
 May show distinct ruptures in the GBM, the severe injury that allows leukocytes, proteins, and
inflammatory mediators to reach the urinary space, where they trigger the crescent formation
 In time, most crescents undergo sclerosis, but restoration of normal glomerular architecture may
be achieved with early aggressive therapy.
65

66. Electron micrograph showing characteristic wrinkling of GBM with focal
disruptions in its continuity (arrows).
66

67. 67

68. 68

69. 69

70. RAPIDLY PROGRESSIVE G.N. (CRESCENTIC G.N.)
Clinical features:
 Most cases present as nephritic syndrome
 Good pasture syndrome patient present With
hemoptysis and life threatening pulmonary
hemorrhages.
 This condition progresses to ARF and death if
untreated.
70

71. NEPHROTIC SYNDROME
71

72. NEPHROTIC SYNDROME
 Clinical condition characterised by massive proteinuria of more 3.5
gm/day, hypoalbuminemia (serum albumin <3 gm%), generalized edema,
hyperlipidemia and lipiduria.
72

73. Pathogenesis of proteinuria:
 Derangement in glomerular capillary walls resulting in increased
permeability to plasma proteins.
 The glomerular capillary wall, with its endothelium, GBM, and
visceral epithelial cells, acts as a size and charge barrier through
which the plasma filtrate passes.
 Increased permeability resulting from either structural or
physicochemical alterations allows protein to escape from the
plasma into the urinary space.
73

74. Types of proteins lost in the urine
 Largest proportion of protein lost - Albumin.
 Highly selective proteinuria: Low molecular weight proteins
like albumin and transferrin are lost.
 Poorly selective proteinuria: Higher molecular weight
globulins are lost along with albumin.
74

75. Grading of Proteinuria.
Normal proteinuria:
Microalbuminuria:
Macroalbuminuria or gross
proteinuria:
Massive proteinuria:
< 30 gm/day.
30 gm/day but <
300 gm/day.
> 300 gm/day.
> 3.5 grams/day.
75

76. Pathogenesis of Hyperlipedemia & Lipiduria.
Increased lipoprotein synthesis
Decreased lipid catabolism
Abnormal lipid transport
HYPERLIPEDEMIA
INCREASED EXCRETION OF
LIPOPROTEIN
Lipiduria
76

77. Pathogenesis of edema
Increased protein loss Increased renal catabolism of
filtered protein
HYPOALBUMINEMIA
DECREASED PLASMA ONCOTIC PRESSURE
GENERALISED EDEMA
77

78. Pathophysiology of Nephrotic
Syndrome. INCREASED GLOMERULAR PERMIABILITY
PROTEINURIA
LOSS OF COAGULATION FACTORS
THROMBOSISMALNUTRITION
INFECTIONS
LOSS OF I G
HYPOALBUMINEMIA
EDEMA
INCREASED LIPOPROTEIN
SYNTHESIS
HYPERLIPEDEMIA
LIPIDURIA
INCREASED PLATELET AGGREGATION
78

79. Molecular basis of nephrotic
syndrome.
NEPHRIN IS AN IMPORTANT PROTEIN AND MUTATION OF NEPHRIN GENE IS
SEEN IN-
1. MINIMAL CHANGE DISEASE
2. FOCAL SEGMENTAL GLOMERULAR SCLEROSIS.
3. CONGENITAL NEPHROTIC SYNDROME OF FINNISH TYPE.
79

80. ETIOLOGY:
 Primary or secondary.
 Primary is more common in children
 Secondary is more common in adults.
80

81. PRIMARY LESIONS:
 Membranous glomerulopathy.
 Minimal change disease (MCD).
 Focal segmental glomerulosclerosis (FSGS).
 Membranoproliferative glomerulonephritis.
 IgA nephropathy.
81

82. Secondary causes
 Diabetes mellitus. Drugs-gold,
Pencillamine.
 Amyloidosis.
 Neoplastic condition-carcinoma and
lymphoma
 Infections- Malaria, syphilis, HBV, AIDS.
 S L E
 Henoch-Scholein purpura.
82

83. MEMBRANOUS GLOMERULOPATHY
 Immune complex mediated disease in which deposits of mainly
IgG and complement collect in the epithelial side of basement
membrane with diffuse thickening of glomerular capillary wall.
 Most common cause of nephrotic syndrome in adults (40%)
83

84. Causes:
1. Idiopathic in 85% cases.
2. Secondary in 15% cases.
Drugs: pencillamine, NSAID, gold,captopril.
SLE.
Infections: HBV, HCV, Syphilis, malaria.
Malignancy: Melanoma, carcinoma lung and colon.
84

85. PATHOGENESIS
 Membranous glomerulopathy is a form of chronic immune
complex–mediated disease.
 In secondary membranous glomerulopathy, the inciting
antigens can sometimes be identified in the immune
complexes.
 For example, membranous glomerulopathy in SLE is
associated with deposition of autoantigen-antibody
complexes.
85

86. PATHOGENESIS
 Susceptibility to Heymann nephritis in rats and membranous
glomerulopathy in humans is linked to the major
histocompatibility complex locus, which can influence the
ability to produce antibodies to the nephritogenic antigen.
 Thus, idiopathic membranous glomerulopathy, like Heymann
nephritis, is considered an autoimmune disease linked to
susceptibility genes and caused most likely by antibodies to a
renal autoantigen.
86

87. PATHOGENESIS
Glomerular capillary wall become leaky in membranous
glomerulopathy
 There is a paucity of neutrophils, monocytes, or platelets in
glomeruli.
 Presence of complement and corroborating experimental
work suggest a direct action of C5b-C9, the pathway leading
to the formation of the membrane attack complex.
 C5b-C9 activates glomerular epithelial and mesangial cells,
inducing them to liberate proteases and oxidants, which cause
capillary wall injury and increased protein leakage.
87

88. MORPHOLOGY.
Light microscopy:
 Almost all the glomeruli are involved
 Uniform, diffuse thickening of glomerular capillary wall.
As the disease advances,
 sclerosis may occur in glomeruli
 The epithelial cells of the proximal tubules contain protein
reabsorption droplets
 Interstitial mononuclear cell inflammation
88

89. 89

90. ELECTRON MICROSCOPY:
 Thickening is seen to be caused by irregular dense deposits of
immune complexes between the basement membrane and the
overlying epithelial cells, the latter having effaced foot
processes.
 Basement membrane material is laid down between these
deposits, appearing as irregular spikes protruding from the
GBM. These spikes are best seen by silver stains,
90

91. 91

92. IMMUNOFLOURESCENCE:
 Granular deposits of immune complex containing IgG and C3 are
demonstrated.
92

93. 93

94. CLINICAL COURSE
 Manifest as nephrotic syndrome.
 Heamaturia and mild hypertension in 15-35% cases
 10 % patients gradually progressive to RF.
94

95. MINIMAL CHANGE DISEASE.
(LIPOID NEPHROSIS)
 Diffuse loss of foot process of visceral epithelial cells (podocytes) in
glomeruli.
 Appear normal on light microscopy.
 Common in children 2—6 yrs.
 Dramatic response to steroid treatment.
95

96. Etiopathogenesis of MCD.
IMMUNE DYSFUNCTION
ELABORATION OF CYTOKINE LIKE SUBSTANCE THAT AFFECTS
VISCERAL EPITHILIAL CELLS.
DEFECT IN CHARGE BARRIER DUE TO LOSS OF FOOT PROCESSES
DETACHMENT OF EPITHELIAL CELLS
PROTEINURIA
96

97. Etiopathogenesis.
 Association with respiratory infection and immunisation.
 Dramatic response to steroid.
 Associated with other atopic disorders.
 Increased incidence in patients with defective T-CELL Mediated immunity as in
Hodgkin’s disease.
97

98. MORPHOLOGY
GROSS:
 Kidneys appear normal.
Light Microscopy:
 Glomeruli appear normal.
 Lipid vacuolation is seen in the proximal convoluted Tubular cells.
98

99.  MINIMAL CHANGE DISEASE.
99

100. Morphology of M.C.D.
(PAS STAIN)
NORMAL BASEMENT MEMBRANE AND
ABSENCE OF PROLIFERATION
100

101. Electron microscopy
 Diffuse loss of foot Processes in visceral epithelial
cells.
Immunoflourescence
 No Ig or complement deposits.
101

102. 102

103. Clinical course
 Commonest in children .
 Present as Nephrotic Syndrome.
 Highly selective proteinuria.
 Renal function is good.
 Prognosis is good.
103

104. FOCAL SEGMENTAL
GLOMERULOSCLEROSIS
 Focal segmental glomerulosclerosis (FSGS) defines a characteristic
pathologic pattern of glomerular injury and is not necessarily a distinct
disease.
 The hallmark of kidney biopsy is an increased degree of scarring seen on
light microscopy of some but not all of the glomeruli present (focal) that
involves some but not all portions of the affected glomeruli (segmental).
 Characterized by proteinuria commonly in nephrotic range.
 Predominant cause of idiopathic nephrotic syndrome in adults.
104

105. CLASSIFICATION
 As a primary disease (idiopathic focal segmental glomerulosclerosis)
 In association with other conditions - HIV infection, heroin addiction, sickle-cell
disease,massive obesity
 As a secondary event- scarring of previously active necrotizing lesions, in cases of
focal glomerulonephritis (e.g., IgA nephropathy)
 Adaptive response to loss of renal tissue (renal ablation), whether from congenital
anomalies (e.g., unilateral renal agenesis or renal dysplasia) or acquired causes (e.g.,
reflux nephropathy), or in advanced stages of other renal disorders, such as
hypertensive nephropathy.
 In uncommon inherited forms of nephrotic syndrome where the disease may be
caused by mutations in genes that encode proteins localized to the slit diaphragm,
e.g., podocin, α-actinin 4, and TRPC6 (transient receptor potential calcium
channel-6)
105

106. Pathogenesis.
 Epithelial damage is the hallmark of FSGS.
 Mechanisms of epithelial damage:
circulating factors and genetically determined defects affecting
components of the slit diaphragm complex.
The hyalinosis and sclerosis stem from entrapment of plasma proteins
in extremely hyperpermeable foci and increased ECM deposition.
106

107. LIGHT MICROSCOPY
 May involve only a minority of the glomeruli and may be missed.
 In the sclerotic segments there is collapse of capillary loops, increase in
matrix and segmental deposition of plasma proteins along the capillary
wall (hyalinosis).
 The hyalinosis may become so pronounced as to occlude the capillary
lumen.
 Lipid and foam cells are often present.
 Glomeruli that do not show segmental lesion usually appear normal.
107

108. 108

109. COLLAPSING
GLOMERULOPATHY
 It is clinically and
pathologically distinct variant
of FSGS
 Characterized by widespread
collapse of glomerular
capillary loops.
 Poor prognosis
 It can occur as an idiopathic
disease or as secondary
process associated with i/v
drug abuse or HIV infection.
109

110. On electron microscopy
both sclerotic and
nonsclerotic areas show
diffuse effacement of
foot processes.
There may also be focal
detachment of the
epithelial cells and
denudation of the
underlying GBM
110

111. IgM and C3 may be
present in the
sclerotic areas and in
the mesangium
111

112. MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
 MPGN is best considered a pattern of immune-mediated injury rather than
a specific disease.
 Accounts for 10% to 20% of cases of nephrotic syndrome.
 Characterized by alteration of glomerular cells and leukocyte infiltration.
 Proliferation is predominantly in the mesengium and involves capillary loops also
, hence a synonym mesengiocapillary glomerulonephritis is used.
 Persistent and slowly progressive.
112

113.  Primary MPGN :- when the cause is idiopathic.
 On the basis of distinct ultra structural, immunofluorescence and
pathological findings it is divided into:-
A) Type I MPGN
B) Type II MPGN (dense deposit disease)
C) Type III MPGN (very rare, it is characterized by a mixture of
subepithelial deposits and the typical pathological findings of Type I
disease)
 Secondary MPGN :- when associated with other systemic disorders.
113

114.  Activation of both classical and alternative complement pathways.
 Antigens involved are unknown, sometimes believed to be protein derived from
infectious agents like hepatitis C and B viruses.(planted antigens)
Type II MPGN tends to present with nephritis while MPGN type I presents more
often with nephrotic features.
 There is activation of alternative complement pathway.
 Serum levels of C3 remains low for a longer period than type I disease.
 More than 70% of patients have a circulating antibody termed C3 nephiritic
factor ( C3NeF ).
114

115. LIGHT MICROSCOPY
 Glomeruli are large and hypercellular.
 Hypercellularity - proliferation of cells in the mesengium and endocapillary
also.
 Lobular appearance due to proliferating mesengial cells and increased
mesengeal matrix.
 The GBM is thickened, often segementally.
 The glomerular capillary wall - double contour or tram-track appearance-
caused by “duplication” of the basement membrane (also commonly
referred to as splitting)
115

116. 116

117. 117

118. Secondary MPGN
 Common in adults and arises in the following settings:
 Chronic immune complex disorders- SLE; hepatitis B infection; hepatitis C
infection, usually with cryoglobulinemia; endocarditis; infected
ventriculoatrial shunts; chronic visceral abscesses; HIV infection; and
schistosomiasis, α1-Antitrypsin deficiency
 Malignant diseases, particularly lymphoid tumors such as chronic
lymphocytic leukemia, which are commonly complicated by development
of autoantibodies
118

119. 119

120. 120

121. 121

122. 122

123. IgA NEPHROPATHY
 Characterized by the presence of prominent IgA deposits in the mesengeal
region.
 Diagnosis is made only by immunochemical method.
123

124. PATHOGENESIS
Abnormalities of
immune regulation
increased IgA synthesis
in response to
respiratory or
gastrointestinal exposure
to environmental agents
IgA1-containing
immune complexes are
then trapped in the
Mesengium
activate the alternative
complement pathway
and initiate glomerular
injury
124

125. 125

126. 126

127. 127

128. 128DIABETIC NEPHROPATHY
 The single most common causes of end-stage renal disease.
 All diabetics get hyperfiltration, thickened glomerular
basement membranes and increased mesangial matrix
(diffuse glomerulosclerosis).
 Both the hyperfiltration and the GBM thickening appear to be
secondary to prolonged hyperglycemia.
 In many advanced cases, there is also nodular
glomerulosclerosis ("Kimmelstiel-Wilson lesion"), with round
masses of GBM-mesangial matrix material in the glomerular
tufts.

129. 129
PATHOLOGY
 Diffuse global
thickening of BM
 Nodular sclerosis
 Arteriolosclerosis
 Trapping of serum
proteins
RESULTS
 Glomerulosclerosis
 Arteriolosclerosis 
Hypertension
 Pyelonephritis
 Papillary necrosis

130. 130Nodular glomerulosclerosis (Kimmelstiel-
Wilson)

131. 131

132. 132Minimal Change Disease
Loss of Foot processes

133. 133Focal Segmental Glomerulosclerosis
Hyaline arteriolosclerosis

134. 134

135. 135

136. 136

137. Normal
Proliferative
137

138. 138
Diffuse Endocapillary
Proliferative GN
Immunofluorescence shows
coarse granular deposits
containing immunoglobulin
and complement.

139. 139

140. 140

141. 141Crescentic GN

142. 142Crescent - (Trichrome Stain)

143. 143Goodpasture Syndrome

144. 144
MPGN : lobular pattern (Lobular GN)

145. 145
 glomerular
capillary loops
show two
basements
membranes
giving the
loops a tram
track
appearance
(arrow).

146. 146
Direct immunofluorescence shows mesangial and capillary loop
granular fluorescence.
Cases of idiopathic membranoproliferative glomerulonephritis
usually show positivity for IgG andC3.
Membranoproliferative glomerulonephritis, type I is a
morphologic diagnosis, not an etiologic diagnosis.
Cases of lupus glomerulonephritis and cryoglobulinemic
glomerulonephritis frequently show a membranoproliferative,
type I pattern of injury

147. 147

148. 148

149. 149
membranoproliferative glomerulonephritis, type II (also known as
dense deposit disease) the dense deposits are also found in
the basement membranes of tubules

150. 150Membranous GN

151. 151

152. 152

153. 153

154. 154

155. 155

156. 156
Lupus nephritis

157. 157Nodular glomerulosclerosis (Kimmelstiel-
Wilson)

158. 158

159. 159