Glomerulonephritis---- Notes by our lecturer from the University of Nairobi

1. Glomerulonephritides

3. 3
 Light micrograph of a normal glomerulus. There are only 1 or 2 cells per capillary tuft, the capillary
lumens are open, the thickness of the glomerular capillary wall (long arrow) is similar to that of the
tubular basement membranes (short arrow), and the mesangial cells and mesangial matrix are located
in the central or stalk regions of the tuft (arrows). Courtesy of Helmut G Rennke.

4. 4  Electron micrograph of a normal glomerular capillary loop showing the fenestrated endothelial cell (Endo), the glomerular
basement membrane (GBM), and the epithelial cells with its interdigitating foot processes (arrow). The GBM is thin and no

5. Glomerular diseases constitute some of the
major problems encountered in nephrology;
chronic glomerulonephritis is one of the
most common causes of chronic kidney
disease in humans.
The glomerulus consists of an anastomosing
network of capillaries invested by two
layers of epithelium.

6. The glomerular capillary wall is the filtration unit
and consists of the following structures:
A thin layer of fenestrated endothelial cells.
A glomerular basement membrane (GBM) with a
central layer, the lamina densa, and thinner
peripheral layers, the lamina rara interna and
lamina rara externa.

7. The visceral epithelial cells (podocytes)
The entire glomerular tuft is supported by
mesangial cells lying between the capillaries.

8. Glomerular Diseases
Primary Glomerular Diseases
Minimal-change disease
Focal and segmental glomerulosclerosis
Membranous nephropathy
Acute postinfectious GN
Membranoproliferative GN
IgA nephropathy
Chronic GN

9. Glomerulopathies Secondary to Systemic
Diseases
Lupus nephritis (systemic lupus erythematosus)
Diabetic nephropathy
Amyloidosis
GN secondary to lymphoplasmacytic disorders
Goodpasture syndrome
Microscopic polyangiitis

10. Wegener's granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis-related GN
GN secondary to extrarenal infection
Thrombotic microangiopathy

11. Hereditary Disorders
Alport syndrome
Fabry disease
Podocyte/slit-diaphragm protein mutations

12. Pathogenesis of Glomerular Diseases
Immune mechanisms underlie most types
of primary glomerular diseases and many of
the secondary glomerular diseases.
GN can be induced by antibodies, and
glomerular deposits of immunoglobulins,
often with various components of
complement, are found frequently in patients
with glomerulonephritis.

13. Cell-mediated immune mechanisms may
also play a role in certain glomerular
diseases.

14. Two forms of antibody-associated injury
have been established:
(1) injury resulting from deposition of
soluble circulating antigen-antibody
complexes in the glomerulus.

15. (2) injury by antibodies reacting in situ
within the glomerulus, either with insoluble
fixed (intrinsic) glomerular antigens or with
molecules planted within the glomerulus
In addition, antibodies directed against
glomerular cell components may cause
glomerular injury.

17. Nephritis Caused by Circulating Immune
Complexes
Antigen-antibody complexes trapped in the
glomeruli, where they produce injury,
through the activation of complement and
the recruitment of leukocytes.
Injury may also occur through the
engagement of Fc receptors on leukocytes
independent of complement activation.

18. The glomerular lesions usually consist of
leukocytic infiltration (exudation) into
glomeruli and variable proliferation of
endothelial, mesangial, and parietal
epithelial cells.

19. Electron microscopy reveals the immune
complexes as electron-dense deposits or
clumps that lie at one of three sites: in the
mesangium, between the endothelial cells
and the GBM (subendothelial deposits), or
between the outer surface of the GBM and
the podocytes (subepithelial deposits).
Deposits may be located at more than one
site in a given case.

20. Immune complexes may eventually be
degraded or phagocytosed, mostly by
infiltrating leukocytes and mesangial cells,
and the inflammatory changes may then
subside.

22. Nephritis Caused by In Situ Immune
Complexes
Antibodies react directly with fixed or
planted antigens in the glomerulus.
Spontaneous anti-GBM antibody GN in
humans results from the formation of
autoantibodies directed against the GBM.

23. Deposition of these antibodies creates a
linear pattern of staining when the bound
antibodies are visualized with
immunofluorescence microscopy,

24. The basement membrane antigen
responsible for classic anti-GBM antibody
GN is a component of the noncollagenous
domain of the α3 chain of collagen type IV.
Sometimes the anti-GBM antibodies cross-
react with basement membranes of lung
alveoli, resulting in simultaneous lung and
kidney lesions (Goodpasture syndrome).

25. Antibodies may react in situ with
previously "planted" nonglomerular
antigens, which may localize in the kidney
by interacting with various intrinsic
components of the glomerulus.
Most of these planted antigens induce a
granular pattern of immunoglobulin
deposition as seen by immunofluorescence
microscopy.

26. factors affecting glomerular localization of
antigen, antibody, or complexes includes
the molecular charge and size.

27. Studies show that complexes deposited in
the endothelium or subendothelium elicit an
inflammatory reaction in the glomerulus
with infiltration of leukocytes.
Antibodies directed to epithelium and
subepithelium are largely noninflammatory
and elicit lesions similar to those of
Heymann nephritis or membranous
nephropathy.

28. Cell-Mediated Immune
Glomerulonephritis
T cell-mediated injury may account for the
instances of GN in which either there are no
deposits of antibodies or immune complexes
or the deposits do not correlate with the
severity of damage.

29. Mediators of Immune Injury
A major pathway of antibody-initiated
injury is complement-leukocyte-mediated.
Activation of complement leads to the
generation of chemotactic agents (mainly
C5a) and the recruitment of neutrophils and
monocytes.

30. Neutrophils release proteases, which cause
GBM degradation; oxygen-derived free
radicals, which cause cell damage; and
arachidonic acid metabolites, which
contribute to reduction in GFR.

31. Effect of the C5-C9 lytic component of
complement, which causes epithelial cell
detachment and stimulates mesangial and
epithelial cells to secrete mediators of cell
injury.

32. 32

33. The membrane attack complex also up-regulates
transforming growth factor-β receptors on
podocytes; TGF-β stimulates synthesis of
extracellular matrix, giving rise to altered GBM
composition and thickening.
Antibodies directed to glomerular cell antigens
may also be directly cytotoxic to glomerular
cells.

34. Other mediators of glomerular damage include;
(1) monocytes and macrophages - release a vast
number of biologically active molecules
(2) platelets - release prostaglandins and growth factors

35. (3) resident glomerular cells (epithelial, mesangial, and
endothelial) - secrete mediators such as cytokines
(interleukin 1), arachidonic acid metabolites, growth
factors, nitric oxide, and endothelin
(4) fibrin-related products

36. Other Mechanisms of Glomerular Injury
Podocyte Injury - Such injury is reflected
by morphologic changes in the podocytes.
Nephron Loss - Once any renal disease,
glomerular or otherwise, destroys sufficient
functioning nephrons to reduce the GFR to
30% to 50% of normal, progression to end-
stage renal failure often proceeds.

37. The Nephrotic Syndrome
Refers to a clinical complex that includes
the following:
(1) massive proteinuria, with daily protein
loss in the urine of 3.5 gm or more in adults
(2) hypoalbuminemia, with plasma albumin
levels less than 3 gm/dL
(3) generalized edema
(4) hyperlipidemia and lipiduria.

38. The initial event is a derangement in the
capillary walls of the glomeruli, resulting in
increased permeability to plasma proteins.

39. In children 1 to 7 years of age, nephrotic
syndrome is almost always caused by a
lesion primary to the kidney, whereas
among adults it is often due to renal
manifestations of a systemic disease.

40. Causes of Nephrotic Syndrome
Primary Glomerular Disease
Membranous GN
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative GN
IgA nephropathy

41. 41
Pre urinalysis

42. Systemic Diseases with Renal
Manifestations
Diabetes mellitus
Amyloidosis
Systemic lupus erythematosus
Ingestion of drugs (gold, penicillamine,
"street heroin")

43. Infections (malaria, syphilis, hepatitis B,
HIV)
Malignancy (carcinoma, melanoma)
Miscellaneous (bee-sting allergy, hereditary
nephritis)

44. Minimal-Change Disease (Lipoid
Nephrosis
Most frequent cause of the nephrotic
syndrome in children
 Characterized by glomeruli that have a
normal appearance by light microscopy but
show diffuse effacement of podocyte foot
processes when viewed with the electron
microscope
Most common between ages 1 and 7 years.

45. The cells of the proximal convoluted
tubules are often heavily laden with protein
droplets and lipids, secondary to tubular
reabsorption of the lipoproteins passing
through the diseased glomeruli.

46. Clinical Course
Development of the nephrotic syndrome in
an otherwise healthy child
Renal function is preserved in most
individuals
The protein loss is usually confined to the
smaller serum proteins, chiefly albumin
(selective proteinuria)

48. More than 90% of cases respond to a short
course of corticosteroid therapy;proteinuria
recurs in more than two-thirds of the initial
responders, some of whom become steroid
dependent.
Less than 5% develop chronic renal failure
after 25 years
The prognosis in children with this disorder
is good.

49. Focal and Segmental Glomerulosclerosis
Characterized histologically by sclerosis
affecting some but not all glomeruli (focal
involvement) and involving only segments
of each affected glomerulus.

50. Occur
(1) in association with other conditions,
such as human immunodeficiency virus
infection or heroin abuse (human
immunodeficiency virus nephropathy,
heroin nephropathy)
(2) as a secondary event in other forms of
GN (e.g., immunoglobulin A [IgA]
nephropathy)

51. (3) as a maladaptation after nephron loss
(4) in inherited or congenital forms
resulting from mutations affecting
cytoskeletal or related proteins expressed in
podocytes
(5) as a primary disease.

52. There is a higher incidence of hematuria
and hypertension in persons with this lesion
Proteinuria is nonselective, and response to
corticosteroid therapy is poor

53. At least 50% of individuals with FSGS
develop end-stage renal failure within 10
years of diagnosis.
Adults fare even less well than children.

54. injury to the podocytes is thought to
represent the initiating event of primary
FSGS.
The deposition of hyaline masses in the
glomeruli represents the entrapment of
plasma proteins and lipids in foci of injury
where sclerosis develops.

55. IgM and complement proteins commonly
seen in the lesion are also believed to result
from nonspecific entrapment in damaged
glomeruli.

56. Morphology
The affected glomeruli exhibit increased
mesangial matrix, obliterated capillary
lumens, and deposition of hyaline masses
(hyalinosis) and lipid droplets.
Occasionally, glomeruli are completely
sclerosed (global sclerosis).

57. Immunofluorescence microscopy -
nonspecific trapping of immunoglobulins,
usually IgM, and complement in the areas
of hyalinosis.
Electron microscopy - the podocytes
exhibit effacement of foot processes, as in
MCD.

58. Progression leads to global sclerosis of the
glomeruli with pronounced tubular atrophy
and interstitial fibrosis.
Morphologic variant called collapsing
glomerulopathy characterized by collapse
of the entire glomerular tuft and podocyte
hyperplasia can occur.

59. Clinical Course
There is little tendency for spontaneous
remission of idiopathic FSGS, and responses
to corticosteroid therapy are usually poor.
About 50% of individuals suffer renal
failure after 10 years.

61. Membranous Nephropathy
(Membranous Glomerulonephritis)
Most common between 30 and 50 years of
age.
Characterized morphologically by the
presence of subepithelial immunoglobulin-
containing deposits along the GBM.
Well-developed cases show diffuse
thickening of the capillary wall.

62. Idiopathic in about 85% of cases.
Remainder (secondary membranous
nephropathy), secondary to other disorders,
including:
(1) infections (chronic hepatitis B, syphilis,
schistosomiasis, malaria);
(2) malignant tumors, particularly
carcinoma of the lung and colon and
melanoma;

63. (3) SLE and other autoimmune conditions;
(4) exposure to inorganic salts (gold,
mercury);
(5) drugs (penicillamine, captopril,
nonsteroidal anti-inflammatory agents).

64. Pathogenesis
Membranous GN is a chronic immune
complex nephritis.
Although circulating complexes of known
exogenous (e.g., hepatitis B virus) or
endogenous (DNA in SLE) antigen can
cause membranous nephropathy, it is now
thought that most idiopathic forms are
induced by antibodies reacting in situ to
endogenous or planted glomerular antigens.

65. The membrane attack complex causes
activation of glomerular mesangial cells
and podocytes, inducing them to liberate
proteases and oxidants that can damage
capillary walls, with consequent
perturbations in filtration.

66. Morphology
H&E stain - diffuse thickening of the
GBM.
By electron microscopy - subepithelial
deposits.
The podocytes show effacement of foot
processes.

67. The glomeruli can become sclerosed.
Immunofluorescence microscopy shows
granular deposits of immunoglobulins
and complement along the GBM.

68. Clinical Course
Proteinuria is nonselective, with urinary loss
of globulins and smaller albumin molecules,
and does not usually respond to
corticosteroid therapy.

70. Membranoproliferative
Glomerulonephritis
Manifest histologically by alterations in the
GBM and mesangium and by proliferation
of glomerular cells.
Some individuals present only with
hematuria or proteinuria in the non-
nephrotic range; others have a combined
nephrotic-nephritic picture.

71. There are two major types of MPGN (I and
II) type I being more common (about 80%
of cases).

72. Pathogenesis
Most cases of type I MPGN seem to be
caused by circulating immune complexes,
but the inciting antigen is not known.
Type I MPGN also occurs in association
with hepatitis B and C antigenemia, SLE,
infected atrioventricular shunts, and extra-
renal infections with persistent or episodic
antigenemia.

73. The pathogenesis of type II MPGN, also
known as dense-deposit disease, is less
clear.
The fundamental abnormality appears to be
excessive complement activation, which
may be caused by several mechanisms not
involving antibodies.

74. Morphology
The glomeruli are large, with an accentuated
lobular appearance, and show
proliferation of mesangial and endothelial
cells as well as infiltrating leukocytes
The GBM is thickened, and the glomerular
capillary wall often shows a double contour,
or "tram track," appearance, especially
evident in silver or periodic acid-Schiff
(PAS) stains.

75. This is caused by "splitting" of the GBM
due to the inclusion within it of processes of
mesangial and inflammatory cells extending
into the peripheral capillary loops

76. Type I MPGN is characterized by discrete
subendothelial electron-dense deposits.
By immunofluorescence microscopy, C3 is
deposited in an irregular granular pattern,
and IgG and early complement components
(C1q and C4) are often also present

77. In type II lesions the lamina densa and the
subendothelial space of the GBM are transformed into
an irregular, ribbon-like, extremely electron-dense
structure, resulting from the deposition of material of
unknown composition, giving rise to the term dense-
deposit disease.
C3 is present in irregular chunky and segmental linear
foci in the basement membranes and in the mesangium
in characteristic circular aggregates (mesangial rings).

79. Clinical Course
The principal mode of presentation (in 50%∼
of cases) is the nephrotic syndrome. The
prognosis of MPGN is generally poor.
Dense-deposit disease has a worse
prognosis, and it tends to recur in renal
transplant recipients.

80. The Nephritic Syndrome
The nephritic syndrome is a clinical
complex, usually of acute onset,
characterized by;
(1) hematuria with dysmorphic red cells and
red blood cell casts in the urine
(2) some degree of oliguria and azotemia
(3) hypertension.

81. Lesions that cause the nephritic syndrome
have in common proliferation of the cells
within the glomeruli, accompanied by a
leukocytic infiltrate. The inflammatory
reaction injures the capillary walls,
permitting escape of red cells into the urine,
and induces hemodynamic changes that
lead to a reduction in the GFR.

82. Poststreptococcal Glomerulonephritis
Subacute Bacterial Endocarditis
Lupus Nephritis
Antiglomerular Basement Membrane Disease
IgA Nephropathy
ANCA Small Vessel Vasculitis
Membranoproliferative Glomerulonephritis
Mesangioproliferative Glomerulonephritis

83. Poststreptococcal glomerulonephritis is an
immune-mediated disease involving:
Streptococcal antigens
Circulating immune complexes
Activation of complement in association with
cell-mediated injury.

84. Poststreptococcal glomerulonephritis is
prototypical for acute endocapillary
proliferative glomerulonephritis.
Acute poststreptococcal GN
• 90% of cases affect children between the ages of 2
and 14 years
• 10% of cases are patients older than 40

85. The classic presentation is an acute nephritic
picture with hematuria, pyuria, red blood cell
casts, edema, hypertension, and oliguric renal
failure, which may be severe enough to appear
as RPGN.
Systemic symptoms of headache, malaise,
anorexia, and flank pain (due to swelling of the
renal capsule) are reported in as many as 50%
of cases.

86. Poststreptococcal glomerulonephritis caused by
impetigo and streptococcal pharyngitis:
• Impetigo: 2–6 weeks after skin infection
• Streptococcal pharyngitis: 1–3 weeks after infection

87. Treatment is supportive, with control of
hypertension, edema, and dialysis as needed.
Antibiotic treatment for streptococcal infection
should be given to all patients and their
cohabitants.
There is no role for immunosuppressive therapy,
even in the setting of crescents.

88. Overall, the prognosis is good, with permanent
renal failure being very uncommon (1–3%), and
even less so in children.
Complete resolution of the hematuria and
proteinuria in children occurs within 3–6 weeks
of the onset of nephritis.

89. The renal biopsy in poststreptococcal
glomerulonephritis demonstrates:
• Hypercellularity of mesangial and endothelial cells
• Glomerular infiltrates of polymorphonuclear
leukocytes
• Granular subendothelial immune deposits of IgG,
IgM, C3, C4, and C5-9
• Subepithelial deposits (which appear as "humps")

92. Endocarditis-associated glomerulonephritis is
typically a complication of subacute bacterial
endocarditis.
Particularly in patients who:
• Remain untreated for an extended period of time
• Have negative blood cultures
• Have right-sided endocarditis (IVDU)

93. Grossly, the kidneys in subacute bacterial
endocarditis have subcapsular hemorrhages
with a "flea-bitten" appearance.
Microscopy on renal biopsy reveals a focal
proliferation around foci of necrosis associated
with abundant mesangial, subendothelial, and
subepithelial immune deposits of IgG, IgM,
and C3.

94. The pathogenesis hinges on the renal deposition
of circulating immune complexes in the kidney
with complement activation.

95. Patients present with:
• Gross hematuria
• Microscopic hematuria
• Pyuria
• Mild proteinuria
• RPGN with rapid loss of renal function (less
common)

96. Primary treatment is eradication of the infection
with 4–6 weeks of antibiotics, and if
accomplished expeditiously, the prognosis for
renal recovery is good.

99. Rapidly Progressive (Crescentic)
Glomerulonephritis
RPGN is a clinical syndrome and not a
specific etiologic form of GN.
It is characterized by rapid and
progressive loss of renal function with
features of the nephritic syndrome,
often with severe oliguria and (if
untreated) death from renal failure
within weeks to months.

100. Regardless of the cause, the histologic
picture is characterized by the presence of
crescents (crescentic GN).
Produced in part by proliferation of the
parietal epithelial cells of Bowman's
capsule in response to injury and in
part by infiltration of monocytes and
macrophages.

101. Type I (Anti-GBM Antibody)
Idiopathic
Goodpasture syndrome

102. Type II (Immune Complex)
Idiopathic
Postinfectious/infection related
Systemic lupus erythematosus
Henoch-Schönlein purpura/IgA
nephropathy

103. Type III (Pauci-Immune) ANCA
Associated
Idiopathic
Wegener granulomatosis
Microscopic angiitis

105. Lupus nephritis is a common and serious
complication of systemic lupus erythematosus
(SLE) and most severe in African-American
female adolescents.

106. Thirty to fifty percent of patients will have clinical
manifestations of renal disease at the time of
diagnosis.
Sixty percent of adults and eighty percent of
children develop renal abnormalities at some
point in the course of their disease.

107. Lupus nephritis results from the deposition of
circulating immune complexes:
• Which activate the complement cascade
• Leads to complement-mediated damage
• Leukocyte infiltration
• Activation of procoagulant factors
• Release of various cytokines

108. The most common clinical sign of renal disease is
proteinuria, but hematuria, hypertension,
varying degrees of renal failure, and an active
urine sediment with red blood cell casts can all
be present.

109. Hypocomplementemia is common in patients
with acute lupus nephritis (70–90%) and
declining complement levels may herald a
flare.
Renal biopsy, however, is the only reliable
method of identifying the morphologic variants
of lupus nephritis.

110. Patients with crescents on biopsy may have a
rapidly progressive decline in renal function.
Without treatment, this aggressive lesion has the
worst renal prognosis.

111. Treatment must combine high-dose steroids with
either cyclophosphamide or mycophenolate
mofetil.
Current evidence suggests that inducing a
remission with administration of steroids and
either cyclophosphamide or mycophenolate
mofetil for 2–6 months, followed by
maintenance therapy with lower doses of the
same

114. Patients who develop autoantibodies directed
against glomerular basement antigens
frequently develop a glomerulonephritis
termed antiglomerular basement membrane
(anti-GBM) disease.

115. When they present with lung hemorrhage and
glomerulonephritis, they have a pulmonary-
renal syndrome called Goodpasture's
syndrome.

116. Goodpasture's syndrome appears in two age
groups:
• Young men in their late 20s
• Men and women in their 60–70s
Disease in the younger age group is usually
explosive:
• Hemoptysis
• Sudden fall in hemoglobin
• Fever
• Dyspnea
• Hematuria

117. The performance of an urgent kidney biopsy is
important in suspected cases of Goodpasture's
syndrome to confirm the diagnosis and assess
prognosis.
Renal biopsies typically show focal or segmental
necrosis that later, with aggressive destruction
of the capillaries by cellular proliferation, leads
to crescent formation in Bowman's space

118. The presence of anti-GBM antibodies and
complement is recognized on biopsy by linear
immunofluorescent staining for IgG (rarely
IgA).

119. Prognosis at presentation is worse if the following
• >50% crescents on renal biopsy with advanced
fibrosis
• Serum creatinine is >5–6 mg/dL
• Oliguria is present
• Need for acute dialysis

120. Patients with advanced renal failure who present
with hemoptysis should still be treated for their
lung hemorrhage, as it responds to
plasmapheresis and can be lifesaving.
Treated patients with less severe disease typically
respond to 8–10 treatments of plasmapheresis
accompanied by oral prednisone and
cyclophosphamide in the first 2 weeks.

123. IgA nephropathy is an immune complex-
mediated glomerulonephritis defined by the
presence of diffuse mesangial IgA deposits
often associated with mesangial
hypercellularity.

124. IgA nephropathy is one of the most common
forms of glomerulonephritis worldwide.
There is a male preponderance, a peak incidence
in the second and third decades of life, and rare
familial clustering.

125. Deposits of IgA are also found in the glomerular
mesangium in a variety of systemic diseases,
including:
• Chronic liver disease
• Crohn's disease
• Gastrointestinal adenocarcinoma
• Chronic obstructive bronchiectasis
• Idiopathic interstitial pneumonia
• Dermatitis herpetiformis
• Mycosis fungoides
• Leprosy
• Ankylosing spondylitis

126. The two most common presentations of IgA
nephropathy are recurrent episodes of
macroscopic hematuria during or immediately
following an upper respiratory infection in
children (Henoch-Schönlein purpura) or
asymptomatic microscopic hematuria most
often seen in adults.

127. Rarely, patients can present with acute renal
failure and a rapidly progressive clinical
picture.
Risk factors for the loss of renal function include
the presence of hypertension or proteinuria, the
absence of episodes of macroscopic hematuria,
male, older age of onset, and more severe
changes on renal biopsy.

128. Studies of patients with IgA nephropathy support
the use of angiotensin-converting enzyme
(ACE) inhibitors in patients with proteinuria or
declining renal function.

129. When presenting as RPGN, patients typically
receive:
• Steroids
• Cytotoxic agents
• Plasmapheresis

131. A group of patients with small-vessel vasculitis
(arterioles, capillaries, and venules; rarely small
arteries) and glomerulonephritis who have
serum ANCA positivity.
The antibodies are of two types:
• Anti-proteinase 3 (PR3)
• Anti-myeloperoxidase (MPO)

132. Wegener's granulomatosis (PR3)
Microscopic polyangiitis (MPO)
Churg-Strauss syndrome (MPO)
Belong to this group because they are ANCA-
positive and have a pauci-immune
glomerulonephritis with few immune
complexes in small vessels and glomerular
capillaries.

133. Induction therapy usually includes some
combination of plasmapheresis,
methylprednisolone, and cyclophosphamide.
The steroids are tapered soon after acute
inflammation subsides, and patients are
maintained on cyclophosphamide or
azathioprine for up to a year to minimize the
risk of relapse.

134. Mesangioproliferative glomerulonephritis is
characterized by expansion of the mesangium,
sometimes associated with mesangial
hypercellularity; thin, single contoured
capillary walls; and mesangial immune
deposits.

135. Clinically, it can present with varying degrees of
proteinuria and, commonly, hematuria.

136. Mesangioproliferative disease may be seen in:
• IgA nephropathy
• P. falciparum malaria
• Resolving postinfectious glomerulonephritis
• Lupus nephritis

137. There is little agreement on treatment, but some
clinical reports suggest benefit from use of:
• Inhibitors of the renin-angiotensin system
• Steroid therapy
• Cytotoxic agents

138. Hereditary Nephritis
Refers to a group of hereditary glomerular
diseases caused by mutations in GBM
proteins.
Best-example is Alport syndrome, in which
nephritis is accompanied by nerve deafness
and various eye disorders, including lens
dislocation, posterior cataracts, and corneal
dystrophy.

139. Morphology
Interstitial cells take on a foamy appearance
as a result of accumulation of neutral fats
and mucopolysaccharides (foam cells) as a
reaction to marked proteinuria.
With progression, there is increasing
glomerulosclerosis, vascular sclerosis,
tubular atrophy, and interstitial fibrosis.

140. Electron microscopy;
EARLY - the basement membrane of
glomeruli appears thin and attenuated.
LATE - GBM develops irregular foci of
thickening or attenuation with pronounced
splitting and lamination of the lamina
densa, yielding a "basket-weave"
appearance.

141. Questions?