Membranoproliferative Glomerulonephritis - Diagnostic Road for Etiology - Dr. Gawad

Membrano-Proliferative
Glomerulonephritis

Diagnostic Road for Etiology

Mohammed Abdel Gawad
1

Searching for a cause of GN is like ……..

2

OBJECTIVES
 Introduction before we drive on the road to etiology:
 Epidemiology
 Pathogenesis & Types
 Renal Presentation
 Pathology

 Diagnostic Road for Etiology of MPGN:
 Step 1: Pathology Tips
 Step 2: Age & Sex
 Step 3: History &Examination
3  Step 4: Investigations

OBJECTIVES
 Epidemiology
 Pathology


Epidimiology

 MPGN accounts for 5% to 10% of primary renal
causes of nephrotic syndrome in children and adults

5
Comprehensive Clinical Nephrology, 4th edition, Chapter 21, Page 263

OBJECTIVES
 Epidemiology
 Pathology


Pathogenesis

7

Pathogenesis

8

Pathogenesis

9

Pathogenesis

10 Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis-a new look
at an old entity. N Engl J Med. 2012;366(12):1119-31

Pathogenesis – Nephritic Factors

 Nephritic factors are IgG or IgM autoantibodies

that bind to and stabilize the C3 convertase

of the alternative (C3bBb) or classical (C4b2b) pathway

thus resulting in continued complement activation.

11

Pathogenesis


Causes

13

OBJECTIVES
 Epidemiology
 Pathology


Presentation
F
k
m

 Microscopic hematuria and non-nephrotic proteinuria
(35%),
 Nephrotic syndrome with minimally depressed renal
function (35%),
 Chronically progressive GN (20%),
 RPGN: rapidly deteriorating renal function with proteinuria
and red cell casts (10%).

S
I
I
b
15

Presentation
 From benign and slowly progressive to rapidly progressive
m
 Microscopic hematuria and non-nephrotic proteinuria (35%),
 Nephrotic syndrome with minimally depressed renal function
(35%),
 Chronically progressive GN (20%),
 RPGN: rapidly deteriorating renal function with proteinuria and
red cell casts (10%).

 Systemic hypertension:
 It is resent in 50% to 80% of patients,
 It may occasionally be so severe that the presentation may be
confused with that of malignant hypertension.

16
S
I Comprehensive Clinical Nephrology, 4th edition, Chapter 21, Page 263

OBJECTIVES
 Epidemiology
 Pathology


Classification

 Type I:
 Discerte immune deposits in the mesangium and subendothelial
space.

 Type II (Dense Deposit Disease – DDD):
 Dense ribbon-like deposits along the basement membranes of the
glomeruli, tubules, and Bowman's capsule & mesangium

 Type III:
 Similar to MPGN type I + subepithelial deposits

18
Comprehensive Clinical Nephrology, 4th edition, Chapter 21, Page 265, 266

Classification
Endothelial Cells

GBM

Epithelial Cells

19

Classification
Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells

MPGN I
20

Classification
Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells

MPGN III
21

Classification
Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells Tubules &
Bowman’s
Capsule
Deposits
MPGN II (DDD)
22

Pathology – LM – MPGN I
 Glomeruli show:
 subendothelial deposits, resulting in a thickened capillary wall and
a double contour (tram track) of the glomerular basement
membrane (GBM)
(This appearance results from so-called circumferential mesangial interposition,
whereby mesangial cells, infiltrating mononuclear cells, or even portions of
endothelial cells interpose themselves between the endothelium and the
basement membrane, with new, inner basement membrane being laid down)

 Endocapillary proliferation

 increased mesangial cellularity and matrix

 Lobular appearance

 Sometimes associated to abundant monocytes and neutrophils

28
Fundamental of Renal Pathology, Section II, Chapter 2, Page 31,32


29


30


31


Diffuse lobular simplification of glomeruli in membranoproliferative
glomerulonephritis type 1, caused by extensive endocapillary proliferation
(Jones' silver stain; original magnification, x100)

32
AJKD, Atlas of Kidney Disease, www.ajkd.org


33


34
www.nephropath.com


35


36


37


38
WebPath, http://library.med.utah.edu/WebPath/webpath.html#MENU


39


40


41


See the irregularities of the capillary walls with methenamine-silver stain. In some
capillaries the lumen becomes imperceptible and in others they demonstrate clearly the
double contours (arrows). Between the GBM and the “new GBM-like” there are immune
42 deposits or “interposed” mesangial cells (Methenamine-silver, X400).
www.kidneypathology.com


In some cases it is possible to identify subendothelial deposits. In this case, with the
trichrome stain, we can see those (fuchsinophilic: red) in the internal aspect of the
capillary wall, demonstrating that they are subendothelial (arrows). These deposits can
also be identified, in some cases, with methenamine-silver stain. (Masson’s trichrome,
43
X1000). www.kidneypathology.com


In this image we can see very well the irregular aspect of the capillary wall: the original
GBM (green arrows), the neosynthesized GBM-like material in the internal aspect (blue
arrows) and an interposed nucleus of mesangial cell (red arrow). The cytoplasm of the
mesangial cell is located between both contours in a variable extension (Methenamine-
44
silver, X1000). www.kidneypathology.com

Pathology – LM – DDD

45


Known as type II MPGN, although this name does not seem right since it is
physiopathogenically and morphologically a different disease
46 (Walker PD, et al. Dense deposit disease is not a membranoproliferative
glomerulonephritis. Mod Pathol. 2007;20(6):605-16)


 Endocapillary proliferation is present.

 The basement membranes are thickened and highly
refractile and eosinophilic, with involved areas with strings of
deposits looking like a string of sausages.

 Mesangial Deposits are also present.

 Thickening also affects tubular basement membranes and
Bowman’s capsule.

47


 In dense deposit disease the capillary walls appear rigid, thickened, and with a more
intensely PAS stained center, also observed with trichrome (sometimes fuchsinophilic)
(arrows). In some cases there is slight cellularity increase and in others it can be mesangial
48 (as in this case)


 PAS-positive capillary walls thickening (arrows). (PAS stain, X400).
49

 a) 1-µm thickness stained with
toluidine blue. The linear material
following the basement membrane of
the capillary wall is also evident in
Bowman's capsule (bottom).

 b) A higher magnification of a portion
of the field in (a). The reflection of the
dense material into Bowman's capsule
is seen on the left (arrow). Breaks in
the continuity of the material within the
basement membrane of the capillary
wall can also be seen. Original
magnification

50
Oxford Text Book of Clinical Nephrology, Section III, Chapter 8, Page 527

Pathology – LM – MPGN III
Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells

 Type I and type III MPGN form a morphologic continuum
and thus are not always separable by light microscopy.

51

Pathology – LM

 MPGN may present with crescents

 Fibrosis in chronic cases

52


53


Cellular Crescent

54

Pathology – IF – MPGN I, III
 deposition of IgM, IgG, and C3 in a granular capillary wall
distribution

 Staining for immunoglobulin is usually scanty.

 Staining for C3 is more frequent and constant and
present also in mesangium.

 Often they are elongated and smooth in their external
edge because they are subendothelial and they are
molded to the GBM.

 Staining for classical pathway complement
components (C1q, C4) may also be seen in MPGN type I.

56
Fundamental of Renal Pathology, Section II, Chapter 2, Page 33

Pathology – IF – MPGN I

57

Pathology – IF – MPGN I

Segmental, coarsely granular-to-globular or elongated capillary wall
IgG deposits in membranoproliferative glomerulonephritis type 1
(immunofluorescence with anti-IgG; original magnification, x200).
58

Pathology – IF – DDD
 C3
 C3 staining outlines the capillary wall, and may be
smooth, granular, or discontinuous.
 Mesangial bright granular C3 staining can be
present.

 Neither classical complement pathway components
nor immunoglobulins are detected; this helps
distinguish it from other types of injury with an MPGN
pattern. However, segmental IgM or less often IgG and
very rarely IgA have been reported

59


 Here is intense staining for C3, typically with almost no staining for
immunoglobulin. The capillary wall staining is usually linear or bilinear.
There often are spherical or ring-shaped mesangial deposits that
correspond to the mesangial dense deposits observed by electron
60
microscopy. www.kidneypathology.com


The bright deposits scattered along capillary walls and in the mesangium by
immunofluorescence microscopy with antibody to complement component C3
are typical for membranoproliferative glomerulonephritis, type II.
61


62
www.renaldigest.com


63

Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells Tubules &
Bowman’s
Capsule
Deposits
65

Pathology – EM – MPGN I

66


Mesangial
Deposits
Endothelial Cells

GBM

67
Epithelial Cells


68
Fundamental of Renal Pathology, Section II, Chapter 2, Page 33-35


 numerous dense deposits in subendothelial and mesangial areas
69


Membranoproliferative glomerulonephritis type 1 with multiple, small-to-
medium subendothelial deposits (transmission electron microscopy;
original magnification, x14,000)
70


Membranoproliferative glomerulonephritis type 1. The marked endocapillary
proliferation (proliferating endothelial and mesangial cells) appears to occlude the
capillary lumen. Numerous large subendothelial and occasional mesangial-dense
immune complex-type deposits (bottom middle) are present (transmission electron
microscopy; original magnification, x4,700).
71


Membranoproliferative glomerulonephritis type 1 with multiple, large subendothelial
deposits (transmission electron microscopy; original magnification, x10,000)
72


Membranoproliferative glomerulonephritis type 1. Mesangial interposition is illustrated
at higher magnification, without evident deposits. These changes result in a "tram-
track," double contour of the basement membrane by light microscopy (see Fig 2)
(transmission electron microscopy; original magnification, x54,000)
73

Pathology – EM – DDD
 In DDD, electron microscopy shows replacement of
large sections of the GBM with an extremely electron-
dense (sausge like, ribbon like, band like) band of
homogeneous material, the identity of which remains
unknown.

 Involvement of mesangial regions, Bowman’s capsules,
and tubular basement membranes by the deposits is
common.

74

 In DDD, electron microscopy shows replacement of
Mesangial
large sections of the GBM with an extremely electron-
Deposits
Endothelial Cells
dense (sausge like, ribbon like, band like) band of
homogeneous material, the identity of which remains
unknown.
GBM

 Involvement of Epithelial Cells
mesangial regions, Bowman’s capsules,
Tubules &
and tubular basement membranes by Bowman’s
the deposits is
common. Capsule
Deposits
75


76


77


78


79


 shows GBM as well as mesangial deposits
80

Pathology – EM – MPGN III
Mesangial
Deposits
Endothelial Cells

GBM

Epithelial Cells

81
www.renaldigest.com


82
www.renaldigest.com


83
www.renaldigest.com

Pathology – C3GN

 C3GN has mesangial, subendothelial,
and sometimes subepithelial and
intramembranous deposits

 On the basis of the morphologic
characteristics of C3GN on electron
microscopy, C3GN is most likely to be
termed MPGN I or MPGN III according
to the older classification.

84 Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis--a new look at an
old entity. N Engl J Med. 2012;366(12):1119-31

OBJECTIVES
 Epidemiology
 Pathology


Pathology Tips – Main Scheme



I made some
modifications in this
algorithm



1ry 2ry other
diseases
present
pathologically
like MPGN

89


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

90


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

91
Always check the possibility of secondary cause


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA
Pathology
Tips 1, 2, 3

92

Pathology Tips – Tip 1
Idiopathic MPGN Secondary MPGN
proliferation is typically uniform and injury may be more irregular.
diffuse

93

Idiopathic MPGN Secondary MPGN
proliferation is typically uniform and injury may be more irregular.
diffuse

Comprehensive Clinical Nephrology, 4th edition,
Chapter 21, Page 266
94

Cryoglobulinemia

 Cryoglobulinemic MPGN:
 Intracapillary:
 globular accumulations of eosinophilic material
representing cryoprecipitate.

 more pronounced infiltration of macrophages within
capillary lumina.

95

Cryoglobulinemia - LM

96


See the hypercellularity and diminution of capillary lumens, one of them completely
occluded by a “hyaline thrombus” (arrow). Hyaline thrombi can be seen green,
bluish or reddish depending on the technique used for the trichrome stain and,
probably, on its composition (Masson’s trichrome, X1000).
97


98
www.renaldigest.com


99

Cryoglobulinemia - EM
 Vague wormy or microtubular or finely fibrillar consisting of the
precipitated cryoglobulins

100

Cryoglobulinemia - IF

MPGN HCV

C3 C3
± +
IF IgM, IgG IgM, IgG
+
kappa & lambda
chains

http://www.kidneypathology.com



MPGN HCV

C3 C3
± +
IF IgM, IgG IgM, IgG
+
kappa & lambda
chains

http://www.kidneypathology.com



Globular accumulations of cryoglobulin in the capillary lumens.
These can be seen by light microscopy as hyaline thrombi.
103
http://www.uncnephropathology.org/jennette/tutorial.htm

Autoimmune & Rheumatologic disease

MPGN Autoimmune &
Rheumatologic
diseases
C3 multiple
IF ± immunoglobulins and
 autoimmune diseases IgG
IgM, complement proteins
IgG, IgM, IgA, C1q,
C3, and kappa and
lambda light chains


Appendix A

-IF: 1ry is uniform diffuse, 2ry is irregular

- Cryoglobulins:
-a: LM: hyaline thrombi
-b: EM: vague wormy microtubules
-c: IF: bright ppt in the capillaries

-1ry: C3, IgM, IgG
-HCV IF: C3, IgG, IgM, Kappa, Lambda
-Autoimmune: C3, C1q, IgG, IgM, IgA,
Kappa, Lambda

107


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

108


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

Pathology
Tips 4, 5, 6

109

Paraproteinemias

MPGN Monoclonal
Gammopathy
C3 monotypic
IF ± immunoglobulin with
IgM, IgG kappa or lambda light
chain restriction.


Pathology Tips – Tip 4 Plasma Cell Dyscriasis
(increase number & activity of plasma
cells)
Paraproteinemias
Monoclonal Gammopathy
Polyclonal Gammopathy
(paraproteinemia)
(deposition of polyclonal Ig)
(deposition of monoclonal Ig)

Light Chain Light Chain Light Chain Light Chain
Heavy Chain IgG, C3, , IgG, C3, ,
or or Mainly Mainly

Cast formation in Amyloid fibril
tubules LCDD HCDD Fibrillariy
transformation Glomerulopathy
(cast nephropathy) Immunotactoid GN (granular deposits) (granular deposits)
(fibrils 8-15 nm) (fibrilis 12-22 nm)
(Crystalline deposits) (glomerulonephritis
with organized
monoclonal
microtubular
immunoglobulin
deposits GOMMID)
(microtubules HLCDD
>30nm) AL
(granular deposits)
(primary amyloidosis)

My Own
Plasma Cells

Classification
> 10 % < 10%

112 Myeloma
Multiple
Clonal Cell
Proliferation

Paraproteinemias – Fibrillary GN

approximately 20 nm diameter fibrils
113

Paraproteinemias – Immunotactoid GN

114

Postinfectious GN - LM

 Both disorders give global and diffuse glomerular hypercellularity, and
both may have an infiltrate of neutrophils in the tuft at early stages

 appearance of glomerular basement membranes on sections
stained by periodic acid-methenamine silver:
 In acute postinfective glomerulonephritis, these appear single,
 in subendothelial membranoproliferative glomerulonephritis, these
appear double.

 The glomerular tuft in subendothelial membranoproliferative
glomerulonephritis may appear in distinct lobules

115
Handbook of Renal Biopsy Pathology, 2nd Edition, Chapter 6, Page 121, 122

Postinfectious GN - LM

116
Handbook of Renal Biopsy Pathology, 2nd Edition, Chapter 6, Page 72

Postinfectious GN - IF

MPGN Postinfectious
GN
particularly of particularly of
Deposits complement and complement but often
sometimes of IgG of IgG and IgM as
well
mainly on the outside on the inner aspect of
Site of glomerular capillary loops
capillary loops

117


MPGN Postinfectious
GN
particularly of particularly of
Deposits complement and complement but often
sometimes of IgG of IgG and IgM as
well
mainly on the outside on the inner aspect of
Site of glomerular capillary loops
capillary loops

118


119

Postinfectious GN - EM

 Electron microscopy confirms the distribution of
immune deposits, and shows whether glomerular
basement membranes are single or double.

120
Handbook of Renal Biopsy Pathology, 2nd Edition, Chapter 6

Postinfectious GN - EM

121

IgA Nephropathy

 IgA nephropathy may present pathologically as
MPGN type I pattern

 Differentiate with IF, IgA predominates in IgA
nephropathy

122
Current Diagnosis & Treatment, Nephrology & Hypertension, Chapter 27, Page 243

Appendix B

- Paraprotinemia:
-IF: monoclonal or very rare
polyclonal Ig, Kappa, Lambda light
chains
- EM: characteristic appearance

-Postinfectious:
- LM:
- no double contour
- no lobulation
-IF: IgG, IgM on the inner aspect on
capillary wall
-EM: sybepithelial deposits

- IgA nephropathy: IF of IgA deposits
124

Appendix B

- Paraprotinemia:
-IF: monoclonal or very rare
polyclonal Ig, Kappa, Lambda light
chains
- EM: characteristic appearance

-Postinfectious:
- LM:
- no double contour
- no lobulation
-IF: IgG, IgM on the inner aspect on
capillary wall
-EM: sybepithelial deposits

- IgA nephropathy: IF of IgA deposits
125


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

126


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

Pathology Tip 7

127

Appendix C
No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

Pathology Tip 7

128

Thrombotic Microangiopathy - LM
 In the acute phase:
 endothelial swelling, and fibrin thrombi are present in the
glomerular capillaries.

 In the chronic phase:
 As the process evolves into a reparative and chronic
phase, there are no active thrombotic lesions
BUT
mesangial expansion and remodeling of the glomerular
capillary walls, including double-contour formation, take
place.

How

129


BUT
place.

How

130


BUT
place.

How

131


BUT
place.

 How to deferntiate chronic phase from MPGN?
132

Thrombotic Microangiopathy – IF & EM

MPGN TMA
(Chronic Phase)
C3
IF ±
IgM, IgG

Dense deposits
EM In mesangium
& along capillary
walls


Thrombotic Microangiopathy – IF & EM

MPGN TMA
(Chronic Phase)
C3
IF ± NO complement or Ig
IgM, IgG

Dense deposits
EM In mesangium NO dense deposits
& along capillary
walls


Thrombotic Microangiopathy

135
www.renaldigest.com


136
www.renaldigest.com


137
www.renaldigest.com

Other MPGN Like Pathologies

138

Pathology & Outcome
 The extent of the basement membrane broadening,
(due to mesangial interposition into the basement
membrane), may be a marker of disease severity, in
type I MPGN: focal changes may represent an early
manifestation of the disease and explain the more
favorable outcome in response to treatment. *

 Crescents

 tubulointerstitial lesions.

139
* Current Diagnosis & Treatment, Nephrology & Hypertension, Chapter 28, Page 251


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

140


No C3
no Ig

other
diseases
present
pathologically
like MPGN

1ry 2ry other
diseases
Think of
present
chronic
pathologically
phase of
like MPGN
TMA

141

Always suspect
secondary causes
especially if there is
an evidence

143

OBJECTIVES
 Epidemiology
 Pathology


Age & Sex

 MPGN Type I:
 Idiopathic in children and young adults (primary
kidney disease without systemic manifestations).

 DDD:
 females : males (3:2).
 between 5 and 15 years old.

145

OBJECTIVES
 Epidemiology
 Pathology


Causes

147

Causes

148

History

 Blood transfusion
 Drug abuse
 Dry eye & mouth
 Photosensitivity
 Traveling to tropic areas
 Surgical history: Ventriculoarterial shunt.
 Drugs:
 Graulocyte colony stimulating factor.
 Interferon α therapy
 Family history of GN

149

Examination
HCV & Mixed Cryoglobulinemia
 Meltzer Triad
 Arthralgia
 Myalgia & weakness
 Skin vasculitis (purpura)

 Liver disease
 Cirrhosis
 Portal hypertension

 Other manifestations

150 Cattran. Am J Kidney Dis 1999; 33:1174

Examination
 The arthralgias:
 rarely accompanied by arthritis,
 usually symmetric,
 classically involve the knees, hips, and shoulders.

 The purpura:
 usually painless,
 palpable,
 nonpruritic;
 occurs in “crops” that last 4 to 10 days
 preferentially localizes to the extremities.
151

Examination

152

Examination

 Other manifestations may include:
 ulcerative, vasculitic lesions that classically involve the
lower extremities and buttocks,

 Raynaud’s phenomenon,

 digital necrosis,

 peripheral neuropathy,

153

Examination

154

Examination - DDD
 It may precede the renal disease by many years.
 Partial lipodystrophy:
 preferentially involves the face and upper body may be
present

155

Examination - DDD
 It may precede the renal disease by many years.
 preferentially involves the face and upper body may be
present

156

Examination - DDD
 preferentially involves the face and upper body may be present

Family photographs of a normal young boy (left) who developed partial lipodystrophy
(right) following an attack of measles. He went on to have mesangiocapillary
glomerulonephritis and renal failure.

157

Examination - DDD
 preferentially involves the face and upper body may be present

Family photographs of a normal young boy (left) who developed partial lipodystrophy
(right) following an attack of measles. He went on to have mesangiocapillary
glomerulonephritis and renal failure.

Hereditary deficiencies of the classical pathway of complement (C1q, C2, C4) and of C3
are associated with the development of MPGN in addition to predisposing to lupus and
158 bacterial infections. Comprehensive Clinical Nephrology, 4th edition, Chapter 21, Page 260

Examination - DDD
 Some patients with DDD will have:
 mild visual field
 color defects
 prolonged dark adaptation
 mottled retinal pigmentation (drusen bodies)
 sometimes deterioration of vision.

 Eye examinations should be performed on first presentation and annually
thereafter including:
 dark adaptation,
 electroretinography,
 electro-oculography.

 Indocyanine green angiography of the retina may reveal
dense deposits in the ciliary epithelial basement membrane
(abnormal fluorescent dots) and choroidal neovascularization.

159

Examination

 Examine all lymph node groups
 Auscultate the heart for new murmur
 Search for drug injection marks on hands & thighs.
 Search for malar rash, discoid rash
 Search for oral ulcers

160

Examination

 Examine all lymph node groups
 Auscultate the heart for new murmur
 Search for drug injection marks on hands & thighs.
 Search for malar rash, discoid rash
 Search for oral ulcers

 Don’t miss FEVER
even the low grade one

161

OBJECTIVES
 Epidemiology
 Pathology


Causes

163

Causes

164

Investigations
 1- detection of infections:
 blood, urine, sputum cultures
 HCV Ab
 HBsAg
 HIV Ab
 Polymerase-chain reaction
 serologic tests for viral, bacterial,
and fungal infections.

165

Investigations
 HCV Ab
 HBsAg
 HIV Ab

 2- Cryoglobulins
 3- Rheumatoid factor
 4- C3, C4
 5- anti dsDNA
 6- ANA
 7- Anti Ro
 8- Anti La

166

Investigations
 HCV Ab
 HBsAg
 HIV Ab

 4- C3, C4
 5- anti dsDNA
 6- ANA
 7- Anti Ro
 8- Anti La

 9- ESR
 10- CRP
 11- CBC
167
 12- Blood film

Investigations
 1- detection of infections:  13- CXR
 14- US abdomen & pelvis (searching
 HCV Ab
abscess or RCC)
 HBsAg
 HIV Ab  15- CT (searching abscess or RCC)

 4- C3, C4
 5- anti dsDNA
 6- ANA
 7- Anti Ro
 8- Anti La

 9- ESR
 10- CRP
 11- CBC
168
 12- Blood film

Investigations
 14- US abdomen & pelvis (searching
 HCV Ab
abscess or RCC)
 HBsAg
 HIV Ab  15- CT (searching abscess or RCC)
and fungal infections.  16- ECHO

 4- C3, C4
 5- anti dsDNA
 6- ANA
 7- Anti Ro
 8- Anti La

 9- ESR
 10- CRP
 11- CBC
169
 12- Blood film

Investigations
 blood, urine, sputum cultures  14- US abdomen & pelvis (searching
 HCV Ab abscess or RCC)
 HBsAg
 15- CT (searching abscess or RCC)
 HIV Ab
 serologic tests for viral, bacterial,  16- ECHO
 17- detection of monoclonal gammopathy:
 2- Cryoglobulins  serum and urine electrophoresis
 Immunofixation studies
 4- C3, C4
 free light-chain assays
 5- anti dsDNA
 Positive results necessitate bone
 6- ANA
marrow studies for a more precise
 7- Anti Ro diagnosis..
 8- Anti La

 9- ESR
 10- CRP
 11- CBC
170
 12- Blood film

Investigations
 Hypocomplementemia

MPGN CH50 C3 C4
I ↓ ↓ or N ↓

II (DDD) ↓ ↓ N

III ↓ ↓

171

Investigations


172

Investigations


C3 nephritic factor activity is more common in type II disease, namely 60–70%
of patients, compared to 20–25% of patients with type I or III disease.
Interestingly, this autoantibody is also detectable in up to 50% of patients with
secondary forms of MPGN [1] and even in some healthy individuals [2]
173 [1] Current Diagnosis & Treatment, Nephrology & Hypertension, Chapter 28, Page 251
[2] Comprehensive Clinical Nephrology, 4th edition, Chapter 21, Page 260

Investigations

174

Investigations

Suspect any organism
as a cause of post
infectious MPGN
whenevr there is
evidence of infection
176

Investigations – Alternative Pathway

177

Follow On
www.nephrotube.blogspot.com
&
Facebook Group
NephroTube
178

Hope that it is clear now ….

Thank
You

Gawad
179

Membranoproliferative Glomerulonephritis - Diagnostic Road for Etiology - Dr. Gawad

Recommended

Recommended

More Related Content

Similar to Membranoproliferative Glomerulonephritis - Diagnostic Road for Etiology - Dr. Gawad

Similar to Membranoproliferative Glomerulonephritis - Diagnostic Road for Etiology - Dr. Gawad (20)

More from NephroTube - Dr.Gawad

More from NephroTube - Dr.Gawad (20)

Recently uploaded

Recently uploaded (20)

Membranoproliferative Glomerulonephritis - Diagnostic Road for Etiology - Dr. Gawad