1 Glomerular Diseases

GLOMERULAR
DISEASES
Benito K. Lim Hong III, M.D.

Objectives:
1. To be able to know & understand the mechanism of

glomerular injury
2. To be able to differentiate Nephritic Syndrome from
Nephrotic Syndrome
3. To be able to know the different Primary
Glomerulopathy as to classify them as Nephritic
Syndrome & Nephrotic Syndrome
4. To be able to know the microscopic appearance of each
glomerular injury & able to understand why is it appear
so
Histology of the Kidney
(Anatomy):
(Layers):
(Renal Cortex):
(Renal Medulla):
Glomerular Diseases
 Glomerular injury is a major cause of renal disease:
 Primary Glomerulonephritis – the kidney is the
principal organ involved.
 Secondary Glomerulonephritis – the kidney is one of
the many organ systems damaged by a systemic
disease.
 Chronic Glomerulonephritis – is the most common cause
of chronic renal failure in humans.
 Some glomerular diseases cause mainly the nephritic
syndrome, others cause mainly a nephrotic syndrome, &
some may cause mixtures of both.
Primary Glomerulopathies
1. Acute Proliferative Glomerulonephritis:
a. Poststreptococcal
b. Non-poststreptococcal
2. Rapidly Progressive (Cresentric)
Glomerulonephritis
3. Membranous Glomerulopathy
4. Lipoid Nephrosis (Minimal Change Diseases)
5. Focal Segmental Glomerulosclerosis
6. Membranoproliferative Glomerulonephritis
7. IgA Nephropathy (Berger’s Disease)
8. Focal Proliferative Glomerulonephritis
9. Chronic Glomerulonephritis
Systemic Diseases
1. Systemic Lupus Erythematosus

2. Diabetes Mellitus
3. Amyloidosis
4. Goodpasture’s Syndrome
5. Polyarteritis nodosa
6. Wegener’s Granulomatosis
7. Henoch-Schonlein Purpura
8. Bacterial Endocarditis
Hereditary Disorders
1. Alport’s Syndrome
2. Fabry’s Disease
Pathogenesis of Glomerular Injury
 2 basic mechanisms of glomerular injury:

1. Immune
2. Non-immune
Immune Mechanisms
 Deposition of antigen-antibody complexes in glomeruli

– a major mechanism of glomerular injury, whether they
are formed in situ with glomerular antigens or are trapped
circulating complexes.
I. In situ immune mechanisms, antibodies can be
directed against:
1. Fixed intrinsic antigens
2. Exogenous or Endogenous antigens planted in the
glomerulus because of some affinity to glomerular
structures
Immune Mechanisms
II. With the circulating immune complexes, the antigens

may be endogenous or exogenous.
 In human Glomerulonephritis, the inciting
endogenous or exogenous antigens are frequently
unknown.
 The immune complexes can be visualized by
immunofluorescence microscopy either in a linear
pattern in anti-GBM nephritis or in a granular
pattern in all other types
Immune Mechanisms
 Once immune complexes are deposited in glomeruli,

injury is induced by cellular & soluble mediators,
including:
1. Neutrophils - which release proteases, oxygen free
radicals, & arachidonic acid metabolites in response
to activated complements.
2. Monocytes, Macrophages, & Lymphocytes –
which release cytokines, cytotoxic cell mediators, &
growth factors.
Immune Mechanisms
3. Platelets – which aggregate & release eicosanoids

& growth factors.
4. Resident glomerular cells particularly mesangial
cells – which can initiate inflammatory responses
by releasing cytokines, oxygen-free radicals,
eicosanoids, & endothelin.
5. C5b-C9 – the terminal membrane attack complex of
complement, which causes cell lysis.
Immune Mechanisms
6. Coagulation proteins especially fibrin – which

may stimulate crescent formation in cresentric GN.
7. Hemodynamic regulators. Ex: Eicosanoids, Nitric
Oxide, Endothelin
8. Cytokines. Ex: IL-1, TNF
9. Growth Factors. Ex: TGF-β – important for ECM
deposition in glomerulosclerosis.
Immune Mechanisms
 Once any renal disease, glomerular or otherwise, destroys

sufficient functioning nephrons to reduce the GFR to
about 30 to 50% of normal, progression to end-stage
glomerulosclerosis & renal failure follows although at
variable rate.
 Adaptive changes in glomeruli to increased workload
(hypertrophy & glomerular capillary hypertension
along with systemic hypertension) cause epithelial &
endothelial injury & resultant proteinuria.
Immune Mechanisms
 The mesangial response, involving mesangial cell

proliferation & matrix deposition, & intraglomerular
coagulation cause the glomerulosclerosis.
 The glomerular damage results in further loss of
functioning nephrons & a vicious circle of progressive
glomerulosclerosis (renal ablation glomerulopathy).
Clinical Manifestations of
Renal Disease
 Acute Nephritic Syndrome – Acute onset of usually gross

hematuria, mild to moderate proteinuria, & hypertension.
 Nephrotic Syndrome – Heavy Proteinuria (>3.5g/day),
hypoalbuminemia, severe edema, hyperlipidemia, &
lipiduria (oval fat bodies in urine).
 Asymptomatic Hematuria &/or Proteinuria – Usually a
manifestation of subtle or mild glomerular abnormalities.
Renal Disease
 Acute Renal Failure – recent onset of azotemia with

oliguria or anuria resulting from severe injury to glomeruli,
tubules, interstitium, or blood vessels.
 Chronic Renal Failure –Prolonged uremia, the end result
of all chronic renal diseases.
 Renal Tubular Defects – dominated by polyuria, nocturia,
& electrolyte disorders.
Renal Disease
 Urinary Tract Infection – Bacteriuria &/or pyuria affecting

the kidney (pyelonephritis) or bladder (cystitis).
 Nephrolithiasis – Renal stones causing renal colic &/or
hematuria.
Differentiating Nephritic from
Nephrotic Syndrome
Nephritic Syndrome Nephrotic Syndrome
1. Gross Hematuria 1. Heavy Proteinuria
2. Mild to Moderate (>3.5g/day)
Proteinuria 2. Hypoalbuminemia
3. Hypertension 3. Severe Edema
4. Hyperlipidemia
5. Lipiduria (oval fat bodies in
the urine)
Nephritic Syndrome
1. Acute Poststreptococcal (Proliferative)

Glomerulonephritis
2. Rapidly Progressive (Cresentric) Glomerulonephritis
(RPGN)
Nephrotic Syndrome
1. Membranous Glomerulonephritis (MGN)

2. Minimal Change Disease (MCD) (Lipoid Nephrosis)
3. Focal Segmental Glomerulosclerosis (FSGS)
4. IgA Nephropathy (Berger’s Disease)
5. Focal Proliferative Glomerulonephritis
Nephritic-Nephrotic Syndrome
1. Membranoproliferative Glomerulonephritis (MPGN)

Nephritic Syndrome
Case Scenario
A 9 year old boy was brought by his parent to the ER due to

gross hematuria, & edema of the face, both upper & lower
extremities, & the trunks. The mother claimed that the patient
had previous history of sorethroat & fever 2 weeks ago & give
the patient Lagundi with temporary relief. Patient was brought
by his mother to a family physician for consult regarding the
above symptoms. BP=190/120. Mother was advised by the
family physician to admit the patient & co-managed by a
Pediatric Nephrologist. Physical Appearance of the patient:
Acute Poststreptococcal
Glomerulonephritis (APGN)
 Acute nephritic syndrome (gross hematuria, red cell casts,

& usually moderate proteinuria & edema) presents 1 to 2
weeks after a nephritogenic strains of group A beta-
hemolytic streptococcal infection of the throat or less
commonly the skin (but other bacterial, viral, & parasitic
infections can produce the same disease picture). Serum
complement levels are low & antistreptococcal exoenzyme
(ASO) titers are elevated.
 Pathogenesis:
 It is a representative disease of acute nephritic
syndrome in which inflammation of the glomerulus is
manifested by proliferation of cellular elements
secondary to an immunologic mechanism.
 Acute poststreptococcal glomerulonephritis occurs
predominantly in males and often completely heals,
whereas patients with rheumatic fever often experience
relapsing attacks.
 Pathogenesis:
 Nephritogenicity is mainly restricted to certain M protein
serotypes that have shown nephritogenic potential.
 Specific M types, such as 49, 55, 57, and 60, are most
commonly associated with skin infections.
 In addition, many M protein serotypes do not confer
lifetime immunity.
 It is possible that nephritogenic antigens are present
and possibly shared by streptococci from several
groups (Molecular Mimicry involving M proteins).
 Diagnosis:
1. History & Physical Examination:
 Consider the possibility of acute poststreptococcal
glomerulonephritis in children with symptoms that
may be secondary to hypertension or congestive
heart failure, even in the absence of visible
hematuria or a history of a preceding streptococcal
infection.
 Diagnosis:
2. Urinalysis (U/A): microscopic hematuria
3. Serology: Recent poststreptococcal infection is most
commonly demonstrated by serologic markers for
elevated antibodies to extracellular streptococcal
antigens.
 Diagnosis:
4. Light Microscopy: Diffuse GN (all glomeruli
involved & global hypercellularity) resulting from
proliferation of endothelial, mesangial, & epithelial
cells, & from exudation of neutrophils &
monocytes.
 Diagnosis:
5. Immunofluorescence Microscopy: Granular,
“Starry-Sky” pattern of IgG, IgM, & C3.
6. Electron Microscopy: Subepithelial Hump deposits
(supporting the belief that the mechanism is immune
complex deposition).
Acute Poststreptococcal Glomerulonephritis
(Urine Specimen)
(Gross)
(Light Microscopy)
(Immunofluorescent Microscopy)
(Electron Microscopy)
 Prognosis:
 Clinically, over 95% of children recover.
 A few develop a rapidly progressive form of the disease,
& the remainder progress to chronic renal failure.
 In adults, the epidemic form has a good prognosis,
but only 60% recover after a sporadic form.
 The remainder develop rapidly progressive disease,
chronic renal failure, or delayed but eventual resolution.
Case Scenario
A 7 year old girl was brought by his parent to the ER due to

gross hematuria, edema of the face, both upper & lower
extremities, & the trunks for 1 month. The mother claimed
that the patient had previous history of sorethroat & fever 2
weeks ago prior to the gross hematuria & edema & give the
patient Herbycin with temporary relief. Patient was in
comatose state with signs of respiratory distress. Vital Signs:
BP=Palpatory 40, HR=30 bpm, RR=40 cpm, T=30˚C.
Physical Appearance of the patient:
Rapidly Progressive
Glomerulonephritis (RPGN)
 A disease of the kidney characterized clinically by a rapid

decrease in the glomerular filtration rate (GFR) of at
least 50% over a short period, from a few days to 3
months.
 A syndrome characterized by the accumulation of cells in
Bowman’s space in the form of “crescents” accompanied
by a rapid progressive decline in renal function.
 Most glomeruli demonstrate crescents.
Rapidly Progressive
 RPGN may occur in the course of 3 broad disease groups:
1. Postinfectious RPGN, Complicating RPGN
2. Idiopathic RPGN
3. Systemic Diseases:
a. Systemic Lupus Erythematosus (SLE)
b. Goodpasture’s Syndrome
c. Vasculitis (Polyarteritis nodosa)
d. Henoch-Schonlein Purpura
e. Essential Cryoglobulinemia
Idiopathic Rapidly Progressive
Glomerulonephritis
 Pathogenesis:
 The link between ANCAs and the pathogenesis of
ANCA-associated disease is unclear; however, it is
postulated that ANCAs induce a premature
degranulation and activation of neutrophils at the time of
their margination, leading to the release of lytic enzymes
and toxic oxygen metabolites at the site of injury.
Glomerulonephritis
 Pathogenesis:
 ANCAs react with antigens in the primary granules in
the cytoplasm of neutrophils (antiproteinase-3
[PR3]) and in lysosomes of monocytes (MPO).
Glomerulonephritis
 Diagnosis:
1. History & Physical Examination:
About half the cases of RPGN present without a
history of infection or the presence of systemic
disease.
2. Light Microscopy: Crescentric GN with little or no
immune complex deposition (Pauci-immune
crescentric GN).
3. Immunofluorescent Microscopy: Linear
immunofluorescence patterns in one-fourth of
patients suggesting Anti-GBM disease & Granular
Immune Complexes in the remainder.
Goodpasture’s Syndrome
 This autoimmune disease consists of pulmonary

hemorrhage & acute GN, usually RPGN type.
 The pulmonary hemorrhage occurs most often in smokers,
usually precedes GN, & causes most morbidity & mortality.
Note: renal/pulmonary syndromes can be also caused by
SLE, Wegener’s, Scleroderma, & Systemic Vasculitis.
 Pathogenesis:
 Autoantibodies reacting with the Goodpasture Antigen,
which resides in the noncollagenous portion of the α3
chain of collagen type IV.
 The autoantibodies bind to their reactive epitopes in
the basement membranes and activate the
complement cascade, resulting in tissue injury.
 This is a classic Type II Reaction in the Gell and
Coombs classification of antigen-antibody reactions.
 Pathogenesis:
 Under normal conditions, the alveolar endothelium is a
barrier to the anti–basement membrane antibodies.
However, with increased vascular permeability, antibody
binding to the basement membrane occurs in the
alveoli.
 Therefore, for the deposition of antibody, an additional
nonspecific lung injury that increases alveolar-capillary
permeability is required.
 Pathogenesis:
 A variety of factors that can result in increased alveolar-
capillary permeability have been identified. These
include the following:
1. Increased capillary hydrostatic pressure
2. High concentrations of inspired oxygen
3. Bacteremia
4. Endotoxemia
5. Exposure to volatile hydrocarbons
6. Upper respiratory infections
7. Tobacco smoking
 Pathogenesis:
 Strong evidence exists that genetics play an important
role.
 Patients with specific human leukocyte antigen
(HLA) types are more susceptible to disease and may
have a worse prognosis.
 Prognosis:
 Although dramatic remissions may follow intensive
plasmapheresis, most patients eventually develop
chronic renal failure.
Rapidly Progressive Glomerulonephritis
(Gross)
(Light Microscopy)
Rapidly Progressive
 Prognosis:
 Very Poor (Bleak), with most patients progressing to
chronic renal failure.
Nephrotic Syndrome
Case Scenario
A 39 year old male was brought by his family to the ER due to

edema of the face, both upper & lower extremities, & the
trunks, body malaise, epigastric pain, & elevated BP.
BP=190/120. Serum Creatinine=20 mg/dl (Normal Value=0.5-
1 mg/dl). Physical Appearance of the patient:
Membranous Glomerulonephritis
(MGN)
 Major cause of nephrotic syndrome in adults.

 It can be idiopathic or secondary (30%).
(MGN)
 Pathogenesis:
 Immunoglobulin-containing electron-dense deposits
along the subepithelial side of the GBM.
 In-situ formation or deposition of circulating immune
complexes, involving intrinsic glomerular antigens or
endogenous & exogenous or planted antigens, is
postulated.
(MGN)
 Diagnosis:
1. History & Physical Examination
2. Elevated Serum Creatinine & BUN
3. Elevated Creatinine Clearance
4. Light Microscopy: Diffuse thickening of the
capillary wall, hence the term “membranous”.
5. Immunofluorescence Microscopy: Diffuse granular
pattern along the GBM.
6. Electron Microscopy: Immunoglobulin-containing
electron-dense deposits along the subepithelial
side of the GBM.
Membranous Glomerulonephritis (Gross)
(Light Microscopy)
Case Scenario
A 12 year old boy was brought by his family to the ER due to

edema of the face, both upper & lower extremities, & the
trunks, poor appetite, & elevated BP. BP=160/100. Mother
claimed that the patient’s urine had a foamy appearance.
Physical Appearance of the patient:
Minimal Change Disease (MCD)
(Lipoid Nephrosis)
 Major cause of nephrotic syndrome in children.

 It refers to a histopathologic lesion in the glomerulus that
almost always is associated with nephrotic syndrome.
(Lipoid Nephrosis)
 Pathogenesis:
 MCD is a disorder of T cells, which release a cytokine
that injures the glomerular epithelial foot processes.
 This, in turn, leads to a decreased synthesis of
polyanions.
 The polyanions constitute the normal charge barrier to
the filtration of macromolecules, such as albumin.
 When the polyanions are damaged, leakage of albumin
follows.
(Lipoid Nephrosis)
 Pathogenesis:
 Synaptopodin is a proline-rich protein intimately
associated with actin microfilaments present in the foot
processes of podocytes.
 Greater synaptopodin expression in podocytes is
associated with a significantly better response to
steroid therapy.
(Lipoid Nephrosis)
 Pathogenesis:
 On the other hand, the expression of synaptopodin does
not predict progression of MCD or diffuse mesangial
hypercellularity to focal segmental glomerulosclerosis
(FSGS).
 Thus, this marker could be used in the future to help
determine appropriate therapy.
(Lipoid Nephrosis)
 Diagnosis:
1. Light Microscopy: Normal glomerulus
2. Immunofluorescents Microscopy: No immune
deposits
3. Electron Microscopy: Uniform & Diffuse effacement
of the foot processes of visceral epithelial cells
(Lipoid Nephrosis)
 Prognosis:
 Long term prognosis is excellent for children & adults,
even those with steroid-dependent disease.
 The most characteristic feature of this condition is the
dramatic response to corticosteroid therapy.
Minimal Change Disease (Lipoid Nephrosis)
(Light Microscopy)
Case Scenario
A 54 year old female, diabetic was brought by her family to

the ER due to edema of the face, both upper & lower
extremities, & the trunks, poor appetite, body malaise, &
elevated BP. BP=180/110. Hgt=230 (Normal value=<200).
Serum Creatinine=1.8 mg/dl (Normal value=0.5-1.5 mg/dl).
Focal Segmental
Glomerulosclerosis (FSGS)
 One of the most common causes of primary glomerular

diseases in adults..
 The condition causes asymptomatic proteinuria or
nephrotic syndrome with or without renal insufficiency.
 Generally, FSGS is a progressive form of kidney disease,
accounting for 2.3% of patients with end-stage renal
disease (ESRD).
Focal Segmental
 Pathogenesis:
 The primary lesion is epithelial damage in affected
glomerular segments.
 Foot process effacement, proliferation of mesangial,
endothelial, and epithelial cells in the early stages,
followed by shrinkage/collapse of glomerular
capillaries all lead to scarring (glomerulosclerosis).
Focal Segmental
 Pathogenesis:
 FSGS initially begins in the deeper juxtamedullary
glomeruli and subsequently extends to the superficial
nephrons.
 The characteristic lesion is a segmental solidification
of the glomerular tuft, usually in the perihilar region
and sometimes in the peripheral areas, including the
tubular pole.
Focal Segmental
 Causes:
1. Idiopathic
2. Superimposed on another primary glomerular
disease
3. Associated with loss of renal mass (renal ablation
FSG) as the result of chronic reflux, analgesic
abuse, or unilateral renal agenesis
4. Secondary to other known disorders
Focal Segmental
 Signs & Symptoms:

1. Signs & symptoms of Nephrotic & Nephritic Syndrome
2. Unlike Minimal Change Disease, the proteinuria is
relatively nonselective, & there is progressive
segmental sclerosis (with associated IgM & C3
deposition).
3. Patient with FSGS are more likely to suffer hematuria,
reduced GFR, & hypertension.
Focal Segmental
 Diagnosis:
1. History & Physical Examination
2. Serum Creatinine & BUN
3. Light Microscopy: Sclerosis of some, but not all,
glomeruli (thus it is focal), & in the affected
glomeruli, only a portion of the capillary tuft is
involved (segmental)
Focal Segmental
 Diagnosis:
4. Immunofluorescent Microscopy: Glomeruli or
segments without lesions do not show
immunoglobulins or complement deposition. In the
segments with lesion is identified, very frequently,
deposits of IgM and C3. Occasionally there are
weak deposits of IgG in segments with lesions.
Focal Segmental
 Diagnosis:
5. Electron Microscopy: The sclerosed segments
show increase of the mesangial matrix and
material similar to the one of the basal membrane.
The hyaline segments are homogenous, electron
dense and, in opposition to immune deposits, they
have a not well-defined edge, without the clearness
that show the immunocomplexes; in addition, the
hyaline material can be seen in areas with
sclerosis or capillary collapse. Glomeruli without
segmental lesions show “effacement” or “fusion”
of podocyte foot processes in a variable extension.
Focal Segmental Glomerulosclerosis (FSGS)
(Light Microscopy)
Glomerular basement membrane collapse and effacement of foot processes of podocytes as in
focal segmental glomerulosclerosis. The collapsed glomerular basement membrane (arrows)
has a wrinkled appearance. The overlying foot processes of podocytes are completely effaced
(arrowheads). The swollen cytoplasm of podocytes contains electron-dense membrane-bound
droplets, presumably lipoprotein (LP)
Focal Segmental
 Prognosis:
 Idiopathic FSGS responds poorly to steroids, &
progression to chronic renal failure is common.
 Recurrences are seen in 25% to 50% of patients
receiving allografts.
Case Scenario
A 24 year old female decided to be admitted due to recurrent

gross hematuria for 6 episodes in a week & lasted for 1
month, edema of the face, both upper & lower extremities, &
the trunks, poor appetite, body malaise, & elevated BP. She
claimed that recurrence of gross hematuria noted 3 months
after the resolution of gross hematuria 1 month ago.
BP=180/110. Hgt=230 (Normal value=<200). Serum
Creatinine=1.8 mg/dl (Normal value = 0.5-1.5 mg/dl). Punch
Biopsy done of the kidney revealed (+) IgA deposits on
immunofluorescent microscopy.
IgA Nephropathy
(Berger’s Disease)
 A major cause of recurrent glomerular hematuria,

characterized by mesangial proliferation & IgA
deposition by immunofluorescence microscopy.
IgA Nephropathy
 Pathogenesis:
 The exclusive mesangial deposition of IgA suggests
entrapment of circulating IgA aggregates.
 Defects in regulation of IgA synthesis, secretion, or
clearance have been postulated.
 Similar IgA deposits are seen in Henoch-Schonlein
Purpura in children.
IgA Nephropathy
 Prognosis:
 The hematuria typically lasts for several days & then
subsides, only to recur every few months.
 Although most patients have an initial benign course,
chronic renal failure develops in up to 50% over a period
of 20 years.
 Onset in old age, heavy proteinuria, hypertension,
crescents, & vascular sclerosis portends a poorer
prognosis.
Nephritic-Nephrotic
Syndrome
Case Scenario
A 44 year old male, was brought by her family to the ER due

to edema of the face, both upper & lower extremities, & the
trunks, gross hematuria, poor appetite, body malaise, &
elevated BP. BP=180/110. Serum Creatinine=3.0 mg/dl
(Normal value=0.5-1.5 mg/dl). HBsAg=(+)
Membranoproliferative
Glomerulonephritis (MPGN)
 The name implies both thickened capillary loops &

proliferation of glomerular cells.
 It accounts for 5% to 10% of nephrotic syndrome in
children & adults, but some patients have hematuria or
proteinuria & others demonstrate a combined nephritic-
nephrotic picture.
 Pathogenesis:
 The normal complement system consists of the classic
and alternative pathways. The classic pathway is
activated by the interaction of C1 with an antigen-
antibody complex. This interaction results in the
formation of C4b2a, which is the classic pathway C3b
convertase. The alternative pathway utilizes C3 and
factors B and D to form the alternative pathway
convertase C3b,Bb.
 Pathogenesis:
 Small amounts of C3b are constantly being formed
in the circulation, which are inactivated by factors H
and I. The binding of C3b to a foreign antigen
decreases its affinity for factor H and allows for the
formation of increasing amounts of the alternate
pathway convertase. The classic and alternate
pathway convertases cause C3 activation, forming C3a
and C3b. C3b is an opsonin itself, and C3 convertase
facilitates the activation of the terminal pathway and
the formation of the membrane attack complex C5b-9.
 2 major types:
1. Type I – related to immune complexes. Shows
subendothelial electron-dense deposits &
occasional subepithelial & mesangial deposits of
C3, early complement components (C1q & C4), &
immunoglobulins in a granular manner. Can occur
in patients with SLE, Hepatitis B, Hepatitis C with
cryoglobulinemia, infected ventriculoatrial shunts,
schistosomiasis, α1-antitrypsin deficiency, chronic
liver disease, & certain malignancies.
 2 major types:
1. Type II (Dense-Deposit Disease) – exhibits evidence
of alternate complement pathway activation
(decreased serum C3, properdin, & factor B). Most
have C3 nephritic factor in the serum, an
autoantibody against C3 convertase that stabilizes the
C3 convertase activity. Shows the GBM to contain
very electron-dense material in a ribbon-like
fashion. Subepithelial “hump-like” deposits are
also found occasionally. C3 is present but there
are no early complement components.
 Diagnosis:
1. Light Microscopy: Lobular accentuation from
increased mesangial cellularity. A segmental
increase occurs in the mesangial matrix, and the
peripheral capillary walls are thickened (“Tram-
Track” appearance or double contour) .
2. Immunofluorescent Microscopy: Intense,
peripheral, glomerular, capillary loop deposition of
immunoglobulin G (IgG) in an interrupted linear
pattern corresponding to extensive subendothelial
immune deposits.
 Diagnosis:
3. Electron Microscopy: Electron-dense deposits
between endothelial cells and GBM are
demonstrated; in addition, there are mesangial
deposits. The formation of “new basement
membrane” is demonstrated under the endothelial
cell. There is effacement of foot processes
(podocytes) and occasional subepithelial small
electron-dense deposits.
Membranoproliferative Glomerulonephritis
(Light Microscopy)
Type I (Immunofluorescent Microscopy)
Type II (Immunofluorescent Microscopy)
Type I (Electron Microscopy)
Type II (Electron Microscopy)
 Prognosis:
 Although steroids may slow the progression of
MPGN, about 50% of patients develop chronic renal
failure within 10 years.
 There is high recurrence rate in transplant
recipients, particularly those with type II disease.
Case Scenario
A 46 year old female was brought by her family to the ER due

to edema of the face, both upper & lower extremities, & the
trunks for 1 month, dyspnea, & body malaise. Patient was in
comatose state with signs of respiratory distress. Vital Signs:
BP=Palpatory 40, HR=30 bpm, RR=40 cpm, T=30˚C. Serum
Creatinine=21 mg/dl (Normal Value=0.5-1.5 mg/dl).
Chronic Glomerulonephritis
 An end-stage pool of glomerular diseases fed by a number

of different glomerulonephritides. Some contributors & the
percentage of cases progressing to chronic GN are listed:
1. Rapid Progressive Glomerulonephritis (90%)
2. Focal Segmental Glomerulosclerosis (50% to 80%)
3. Membranoproliferative Glomerulonephritis (50%)
4. Membranous Glomerulonephritis (40%)
5. IgA Nephropathy (30% to 50%)
6. Poststreptococcal Glomerulonephritis (1% to 2%)
 However about 20% of cases arise mysteriously with no

history of any well-recognized form of early GN.
 Because glomeruli in chronic GN are totally replaced
by hyalinized connective tissue, it may be difficult to
know the nature of the antecedent lesion.
Glomerular Lesions Associated
with Systemic Disease:
 Systemic Lupus Erythematosus (SLE):
 5 patterns of Lupus Nephritis:
1. Class I (Normal) - normal by light microscopy, EM,
& fluorescence microscopy; rare.
2. Class II (Mesangial Lupus GN) – present in about
25% of patients; associated with minimal hematuria
or proteinuria. Slight increase in mesangial matrix &
cells with granular mesangial Ig & complement
deposits.

3. Class III (Focal Proliferative GN) – 20% of
patients. Associated with recurrent hematuria,
moderate proteinuria, & occasional mild renal
insufficiency. Focal & segmental glomerular
swelling with endothelial & mesangial proliferation,
neutrophil infiltration, & sometimes fibrinoid
deposits, & capillary thrombi.
4. Class IV (Diffuse Proliferative GN) – 35% to 40%
of patients, many of whom are overtly symptomatic,
with microscopic to gross hematuria, proteinuria
(sometimes nephrotic range), hypertension, &
diminished GFR. Most glomeruli show endothelial,
mesangial, & occasionally epithelial proliferation. IC
deposits are typically subendothelial, & when
extensive form “wire loops”. Frequently, there are
also tubular changes with granular IC deposits in
basement membranes & interstitial changes. Most
severe form of lupus nephritis, carrying the worst
prognosis.

5. Class V (Membranous GN) – 15% of patients,
induces severe proteinuria or nephrotic syndrome.
Diffuse thickened capillary walls similar to idiopathic
membranous GN, & characterized by subepithelial
IC deposits.
 Henoch Schonlein Purpura:
 Purpuric skin lesions (Leukocytoclastic Vasculitis),
abdominal symptoms (pain, vomiting , bleeding),
arthralgia, & GN.
 Vary from Focal Mesangial Proliferation to Crescentic
GN, but are always associated with mesangial IgA
deposition.
 Usually occurs in children, the course is variable & the
resolution of the lesions is the rule.
 However, chronic renal failure may ensue, especially in
those with diffuse lesions or the nephrotic syndrome.
 There is progressive renal failure in those with
crescents.
 Bacterial Endocarditis:
 Variably severe immune complex-mediated GN showing
a morphologic continuum from Focal Necrotizing
GN to diffuse GN, sometimes with crescents.
 Not “embolic” as previously thought.
 Diabetic Glomerulosclerosis:
 Produces proteinuria (sometimes in the nephrotic range)
in 55% of juvenile-onset & 30% of adult-onset diabetics.
 Usually discovered 12 to 22 years after diabetes
appears, & heralds the onset of end-stage renal disease
4 to 5 years later in about 30% of juvenile diabetics.
 Morphologic changes in glomeruli include capillary
basement membrane thickening , diffuse diabetic
glomerulosclerosis, & nodular glomerulosclerosis
(the latter known as Kimmelstein-Wilson Disease).
Kimmelstein-Wilson Disease
 Amyloidosis:
 Amyloid deposited in glomeruli & in vessel walls in
either primary or secondary forms, producing heavy
proteinuria.
 Eventually end-stage renal disease occurs, but the
kidneys tend to be of normal size or slightly enlarged.
 Essential Mixed Cryoglobulinemia – can induce cuta-

neous vasculitis, synovitis, & GN.
 Plasma Cell Dyscracias - can be associated with
amyloidosis, monoclonal cryoglobulinemia, & a peculiar
nodular GN (granular dense deposits) ascribed to the
deposition of non-fibrillary light chains usually of the kappa
type, known as Light-chain Disease.

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GLOMERULAR

Benito K. Lim Hong III, M.D.

1. To be able to know & understand the mechanism of

1. Systemic Lupus Erythematosus

 2 basic mechanisms of glomerular injury:

 Deposition of antigen-antibody complexes in glomeruli

II. With the circulating immune complexes, the antigens

 Once immune complexes are deposited in glomeruli,

3. Platelets – which aggregate & release eicosanoids

6. Coagulation proteins especially fibrin – which

 Once any renal disease, glomerular or otherwise, destroys

 The mesangial response, involving mesangial cell

 Acute Nephritic Syndrome – Acute onset of usually gross

 Acute Renal Failure – recent onset of azotemia with

 Urinary Tract Infection – Bacteriuria &/or pyuria affecting

1. Acute Poststreptococcal (Proliferative)

1. Membranous Glomerulonephritis (MGN)

1. Membranoproliferative Glomerulonephritis (MPGN)

A 9 year old boy was brought by his parent to the ER due to

 Acute nephritic syndrome (gross hematuria, red cell casts,

A 7 year old girl was brought by his parent to the ER due to

 A disease of the kidney characterized clinically by a rapid

 This autoimmune disease consists of pulmonary

A 39 year old male was brought by his family to the ER due to

 Major cause of nephrotic syndrome in adults.

A 12 year old boy was brought by his family to the ER due to

 Major cause of nephrotic syndrome in children.

A 54 year old female, diabetic was brought by her family to

 One of the most common causes of primary glomerular

 Signs & Symptoms:

A 24 year old female decided to be admitted due to recurrent

 A major cause of recurrent glomerular hematuria,

A 44 year old male, was brought by her family to the ER due

 The name implies both thickened capillary loops &

A 46 year old female was brought by her family to the ER due

 An end-stage pool of glomerular diseases fed by a number

 However about 20% of cases arise mysteriously with no

 Systemic Lupus Erythematosus (SLE):

 Systemic Lupus Erythematosus (SLE):

 Essential Mixed Cryoglobulinemia – can induce cuta-

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