Glomerular Syndromes &
Disorders
Nephrotic Syndrome
Immune Mediated
Membranoproliferative
Gromerulonephritis
Membranous
Glomerularnephritis
Non-Immune Mediated
IgA Nephropathy
Focal Segemental
Glomerulonephritis
Minimal Change Disease
Nephritic Syndrome
Chronic Renal Failure
Post-Steptococcal
Glomerulonephritis
Rapidly Progressive
Crescentric
Glomerulonephritis
IgA Nephropathy
Type 1
Type 2
Anti-GBM Antibody
Immune Complex
Pauci-Immune ANCA
Associated
1. Goodpasture
Syndrome
1. Idiopathic
1. Idiopathic
2. Post Infection
2. Idiophatic
3. SLE
2. Wegener
Granulomatosis
4. Henoch-Schonlein
Purpura
Type 3
3. Microscopic Angiitis
Differences Between Nephrotic and Nephritic Syndrome
Nephrotic Syndrome
Nephritic Syndrome

Definition

Causes


Laboratory
Finidngs
Hallmarks
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Condition marked by
o Very high level of protein in the urine
o Low level of protein in the blood
o Anasarca especially at
 Around the eyes
 Feet
 Hands
o Hyperlipideamia
o At onset, little or NO
 Azotemia
 Heamaturia
 Hypertension
It is not a disease by itself, it is a manifestation of other
underlying disease, therefore lots of diseases are associated
with it, such as
o Minimal Change Glumerulonephritis
o Membranous Glomerulonephritis
o Membranoproliferative Glomerulonephritis
o Focal Segmental Glomerulosclerosis
Children due to primary lesion on the kidney, but adult due to
underlying disease such as
o Diabetes Mellitus
o Amyloidosis
o SLE
Proteinuria
o 3.5g/day
Hypoalbuminaemia
Edema
Hyperlipidaemia
Lipiduria
Massive proteinuria
o Loss of protein in the urine at 3.5g or more per day
Hypoalbuminaemia
o Plasma albumin less then 3g/dl
Anasarca
o Obvious clinical manifestation
Hyperlipidaemia and Lipiduria
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It is a clinical complex
Usually an acute onset characterized by
o Heamaturia
o Oliguria
o Azotemia (increase nitrogen level in body)
o Hypertension
Common lesion that can cause Nephritic Syndrome is
o Proliferation of cells within the glomeruli
o Accompanied by Lymphocytic infiltration
o Injury to the capillary walls of the tubule
 Leads to the release of RBC into the urine
 Causing heamodynamic changes that leads to
reduction in GFR
o Reduction of GFR
 Oliguria
 Reciprocal fluid retention
 Azotemia
Proteinuria
Hypoalbuminaemia
Edema
Heamaturia
Oliguria
Hypertension
Heamaturia
Oliguria
Azotemia
Hypertension
Glomerular Syndromes and Disorders
Nephrotic Syndrome
Immune Mediated
Epidemiology, Etiology &
Clinical Features
Diseases
Membranous
Glomerulonephritis
Other names

Epimembranous
Glomerulonephritis

Extramembranous
Glomerulonephritis
40-60 years old
50% of adult Nephrotic Syndrome


Morphology

o
o
o
Etiology ‘
Chronic Immune complex disease
Idiopathic in most patients
Sometimes associated with
o
Infection
o
Drugs
o
Carcinomas
o
Heavy metals
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Clinical Features

o
Children and young adults
5-25 years old
Etiology
Chronic immune complex
glomerulonephritis

Associated with (generally)
o
Chronic infections
o
SLE
o
Cancer
o
Cirrhosis
o
Heroin abuse

Can be further categorized into
2
o
Type 1 – More common

Can be due

Hepatitis B and C

SLE

Infected AV shunt
o
Type 2 (Dense Deposit
Disease)

Can be due

Autoantibodies – C3
Nephritic Factor (C3NEF)

Clinical Features

o
o


Basement Membrane
Diffused
Uniform thickening
Coarsely granular deposits of

IgG

C3
Subepithelial projection (spikes)
Electron dense Subepithelial
deposits

Diffuse proliferative basement
membrane
Thickening of glomerular
capillary walls
Splitting of glomerular basement
membrane (tram-tracking)
Diffuse coarse deposits of IgG
and C3 along the GBM
Electron dense subendothelial
deposits

o
o

Non-selective proteinuria
Albumin
Globulin
With or without heamaturia
Clinical Course

Prognosis
Children

Excellent
o
Adults

Some develop End Stage
Renal Disease (ESRD)
o
Nephrotic Syndrome in 80%
Assymptomatic proteinuria in 20%
Microscopic Hematuria
Indolent course
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Membranoproliferative
Glomerulonephritis
Laboratory Findings
Can be either
Nephrotic Syndrome 50%
Acute Nephritic Syndrome 20%
Recent history of URTI in 50%
Hypertension with/out renal
insufficiency
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Specifically

Type 1
o
Subendothelial deposits

Type 2
o
Intramembranous deposits
Decrease in complement
proteins
o
Classical pathway
o
Alternative pathway

C3 Nephritic Factor (C3NEF)

Circulating immune complex

Prognosis
Generally poor prognosis
Development of ESRD within
10 years

Children – 50%

Adults – 80%
o
Progressive deterioration of
renal function with/out short
remission
o
o
Glomerular Syndromes and Disorders
Nephrotic Syndrome
Non-Immune Mediated
Epidemiology, Etiology &
Clinical Features
Diseases
Minimal Change
Glomerulonephritis
Other names

Nil Disease

Lipoid Nephrosis

Foot Process Disease
Male
Incidence
o
Children 1-8 yrs old
o
Adults 20-30 yrs old

80% Nephrotic Syndrome in
children
Etiology

Idiopathic

Maybe
o
T-cell derived factor
o
Loss of net negative charge
on capilarry basement
membrane
Clinical Features

Insidious Nephrotic syndrome

History of URTI – 30% of cases

Associated with Hodgkin’s
Lymphoma

Sometimes overlap with FSGS
patients

Without Hypertension


10% of all cases of Nephrotic
Syndrome
Common in adult rather than
children


Focal Segmental
Glomerulosclerosis

Lesion characterized by
o
Sclerosis affecting

Somepart of glomeruli

Focal involvement

Some part of a given
glomerulus

Segemental
involvement
Etiology


o
o
o
o
o
Most are idiopathic Nephrotic
Syndrome in adults
Due to
HIV, heroin abused
Secondary event to IgA
Nephropathy
Maladaptation to nephron loss
Congenital anomalies
affecting the cytoskeleton of
Podocytes
Idiopathic
Morphology
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o
o
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o
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o
o
o
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o
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o
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o
o
o
Laboratory Findings
Light Microscope
Normal finding
Tubular appearance

Protein droplets

Lipids

These are due to to
reabsorption of
lipoprotein in the
Proximal Convulated
Tubule
Immunoflourescent
Negative; no remarkable
findings, No Ag/Ab compolex
Electron Microscope
Efacement of Podocytes
processes
Focal fusion
Loss of foot processes

Light Microscope
Focal segmental glomerular
collagenous sclerosis
Immunoflourescent
Deposition of IgM and
complement protein

In the areas of hyalinosis
Electron Microscope
Visceral epithelial cells exhibit
loss of foot processes
Grate degree of epithelial cells
detachment
Denudation of underlying GBM
Clinical Course
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
Selective proteinuria
Confined to smaller Albumin
No specific lab findings

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Urinalysis
Blood test

o
o
o
o

Prognosis
Spontaneous recovery 25-40%
Complete recovery 65-70%
Steroid resistance pts may
progress to FSGS
50% individuals with FSGS
develop ESRD within 10 years of
time
Children has better prognosis
compared to adults
Glomerular Syndromes and Disorders
Nephritic Syndrome
Epidemiology, Etiology &
Clinical Features
Diseases
Peak incidence in children
3-14 years old

Sporatic in nature
o Mostly happens during
winter and spring
Etiology

Ab/Ag complex from
o Beta hemolytic
streptococci

Group A

Type 12

o
Acute Post-Streptococcus
Glomerulonephritis
Other names

Acute Proliferative
Glomerulonephritis

Acute Post-infectious
Glomerulonephritis
Clinical Features

Acute Nephritc Syndrome

Post streptococcal
pharyngitis and other
infections

Categorized into 3 types
Type 1

Anti GMB disease
o Type 2

Immune-complex
mediated disorder
o Type 3

Pauci-immune type of
CrGN
o
Rapidly Progressive
Crescentric
Glomerularnephritis (CrGN)
Morphology
Glomeruli
Enlarged
Hypercellular

Proliferation of
o Endothelial cells
o Mesengial cells

Evidence of acute
inflammation

Basement membrane
o Deposition of IgG and C3
o Appeared coarsely
granular pattern along the
GBM

Immunes deposits are
distributed in the capillary
loops
o
In granular, bumpy pattern
o Due to the focal nature of
immune complex
deposition process
Gross

Kidneys appaer
o Enlarged
o Pale
o Petechial heamorrhage on
cotex
Microscopy

Light microscope
o Glomeruli surrounded by
crescents
o Crescents are formed by

Proliferation of partial
cells

Migrations of Monocytes
and Macrophages into
Bowman’s capsule

Immunoflourescent
o Fibrin arranged in the
crescents
o Ig are absent

Electron Microscope
o Rupture of GBM
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Laboratory Findings
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o
o
o
o
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
Nephritic Urine with
RBC casts
Evidence of streptococcal
infection
Serologic evidence of recent
infection
Decreased serum level of
complement
Serological markers
Type 1

Anti-GBM antibodies
o Type 2

Circulating immune
complex
o Type 3

Anti-Neutrophil
Cytoplasmic Antigen
(ANCA)
Clinical Course

Prognosis
Children

Best prognosis
o Adult

Worse prognosis

Some develop
progressive disease
o
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o
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Rapidly progressive loss of
renal function
Nephritic Syndrome
Progress to renal failure
Can present with acute
renal failure
Progression to Ureamia is
rapid unless prompt
treatment is initiated
Glomerular Syndromes and Disorders
Nephritic Syndrome
Diseases
IgA Nephropathy
(Buerger Disease)
Epidemiology, Etiology &
Clinical Features
 Young adults 15-30 years
old
 Most common type of
Glomerulonephritis
Etiology
 IgA deposits in the
mesangium
Clinical Features
 Assymtomatic
heamaturia – 40%
o Happens within 1-2 days
during URTI
 Macro heamaturia – 40%
 Nephrotic syndrome -10%
 Renal failure – 10%
Very rare familial renal
disease
 More common in males
Etiology
 Genetic defect resulting
in disturbance in
composition of the
basement membrane
 X-linked disease
Clinical Features
 Often associated with
nerve deafness
 Gross and micro
heamturia
 Normal level of serum
creatinine
 Collagen type4

Hereditary Nephritis
(Alport Syndrome)
Morphology
Laboratory Findings
Light Microscope
Mesangial widening
Segemental inflammation
Diffuse mesangial
proliferation or crescentic
glomerulonephritis may
also be present

Immunoflourescent
o mesangial deposition of
IgA often with C3 and
properdin and smaller
amounts of other
immunoglobulins (IgG or
IgM)

Electron Microscope
o Electron-dense deposits in
the mesangium that may
extend to the
subendothelial area of
adjacent capillary walls in
a small subset of cases,
usually those with focal
proliferation.


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Localized
involvement
of kidney
Idiopathic
Light Microscope
Segmental glomeruli
 Proliferation
 Sclerosis
o Interstitial foam cells are
frequent
 Immunoflourescent
o Absence of Ig
deposition
 Electron Microscope
o Glomerular capillary
basement membrane
appears
 Thickened
 Split
 Splintered


Heamaturia
Electromicroscopy

o
o
o

o
Heamaturia
Protein electrophoresis
IgA immunoglobulin increased
Clinical Course

o
o
o
o
o
o
Difference
Buerger Disease

Poor prognosis in
patient with
Hypertension
Proteinuria
Male gender
Smoking
Hyperlipidaemia
Older age
Henoch-Scheloin
Purpura
 Systemic
manifestation
of a disease
 Presented with
o GIT
disturbance
o Arthritis
o Skin rash and
purpura

Prognosis
Males who
develop renal
failure and ESRD
in early
adulthood
 Por prognossi
o Women
 Variable
prognosis
o