Membranoproliferative glomerulonephritis (MPGN) is characterized by alterations in the glomerular basement membrane and mesangium as well as proliferation of glomerular cells. There are two main types of MPGN, type I and dense deposit disease (formerly type II), which are pathological entities with distinct features. Type I MPGN, which is more common, can be caused by circulating immune complexes or planted antigens, while dense deposit disease appears to be due to excessive complement activation from C3 nephritic factor. Both present variably with hematuria, proteinuria, or nephrotic syndrome and carry poor prognoses, with dense deposit disease being worse.

1. DR. SHAGUN HARSH
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS

2.  Membranoproliferative GN (MPGN) is
manifested histologically
by alterations in the GBM and mesangium
and by
proliferation of glomerular cells
 Some patients present only with hematuria
or proteinuria in the non-nephrotic range;
others exhibit a combined nephrotic–
nephritic picture.

3.  Two major types of
 MPGN (I and II) have traditionally been
recognized on the basis of distinct
ultrastructural, immunofluorescence,
microscopic, and pathogenic findings
 But these are now recognized to be separate
entities, termed MPGN type I and dense
deposit disease (formerly MPGN type II)
 MPGN type I is far more common (about 80%
of cases).

4.  Some cases of type I MPGN may be caused by-
 circulating immune complexes, akin to chronic
serum sickness, or may be due to a planted
antigen with subsequent in situ immune complex
formation.
 Type I MPGN alsooccurs in association with
 hepatitis B and C antigenemia,
 systemic lupus erythematosus,
 infected atrioventricular shunts, and
 extrarenal infections with persistent or episodic
antigenemia.

5.  The fundamental abnormality in dense
deposit disease (MPGNType II) appears to
be excessive complement activation.
 Some patients have an autoantibody against
C3 convertase, called C3 nephritic factor,
which is believed to stabilize the enzyme and
lead to uncontrolled cleavage of C3 and
activation of the alternative complement
pathway.

6. LIGHT MICROSCOPY
 By light microscopy, type I MPGN and many
cases of dense deposit disease are similar
 The glomeruli are large, with an accentuated
lobular appearance, and show proliferation
of mesangial and endothelial cells as well as
infiltrating leukocytes

7. Membranoproliferative glomerulonephritis (MPGN), showing
mesangial cell proliferation, basement membrane thickening,
leukocyte
infiltration, and accentuation of lobular architecture

8.  The GBM is thickened, and the glomerular
capillary wall often shows a double contour, or
“tram track,” appearance, especially evident
with use of silver or periodic acid–Schiff (PAS)
stains
 This “splitting” of the GBM is due to extension
of processes of mesangial and inflammatory
cells into the peripheral capillary loops and
deposition of mesangial matrix

9.  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) often are also present, indicative of an
immune complex pathogenesis

10.  By contrast, in the aptly named dense
deposit disease 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.

11. CLINICAL COURSE
 The principal mode of presentation (in
approximately 50% of cases) is the nephrotic
syndrome, although MPGN or dense deposit
disease may begin as acute nephritis or mild
proteinuria.
 The prognosis of MPGN type I generally is
poor.

12.  Dense deposit disease carries an even worse prognosis, and
it tends to recur more frequently in renal transplant
recipients
 MPGN type I may occur in association withother disorders
(secondary MPGN), such as
 systemic lupus erythematosus,
 hepatitis B and C,
 chronic liver disease,
 chronic bacterial infections.
 Indeed, many so-called idiopathic cases are believed to be
associated with hepatitisC and related cryoglobulinemia.

13. THANKYOU