Page 541 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster
P. 541
Glomerular Diseases 527
Membranoproliferative Glomerulonephritis and
Dense Deposit Disease
Membranoproliferative GN (MPGN) is manifested histo-
logically by alterations in the GBM and mesangium and by
proliferation of glomerular cells. It accounts for 5% to 10%
of cases of idiopathic nephrotic syndrome in children
and adults. Some patients present only with hematuria or
proteinuria in the non-nephrotic range; others exhibit a
combined nephrotic–nephritic picture. 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). Of the
two types of disease, MPGN type I is far more common
A (about 80% of cases).
Podocyte with effaced PAT H O G E N E S I S
foot processes
Different pathogenic mechanisms are involved in the devel-
Thickened opment of MPGN and dense deposit disease.
basement • Some cases of type I MPGN may be caused by
membrane
circulating immune complexes, akin to chronic
Subepithelial serum sickness, or may be due to a planted antigen with
deposits subsequent in situ immune complex formation. In either
"Spikes" case, the inciting antigen is not known. Type I MPGN also
occurs in association with hepatitis B and C antigenemia,
B systemic lupus erythematosus, infected atrioventricular
shunts, and extrarenal infections with persistent or epi-
Figure 13–8 Membranous nephropathy. A, Diffuse thickening of the sodic antigenemia.
glomerular basement membrane (periodic acid–Schiff stain). B, Sche- • The pathogenesis of dense deposit disease is less clear.
matic diagram illustrating subepithelial deposits, effacement of foot pro- The fundamental abnormality in dense deposit
cesses, and the presence of spikes of basement membrane material disease appears to be excessive complement acti-
between the immune deposits. vation. Some patients have an autoantibody against C3
convertase, called C3 nephritic factor, which is believed
Clinical Course to stabilize the enzyme and lead to uncontrolled cleavage
Most cases of membranous nephropathy present as full- of C3 and activation of the alternative complement
blown nephrotic syndrome, usually without antecedent pathway. Mutations in the gene encoding the complement
illness; other individuals may have lesser degrees of pro- regulatory protein factor H or autoantibodies to factor
teinuria. In contrast with minimal-change disease, the pro- H have been described in some patients. These abnor-
teinuria is nonselective, with urinary loss of globulins as malities result in excessive complement activation. Hypo-
well as smaller albumin molecules, and does not usually complementemia, more marked in dense deposit disease,
respond to corticosteroid therapy. Secondary causes of is produced in part by excessive consumption of C3 and
membranous nephropathy should be ruled out. Membra- in part by reduced synthesis of C3 by the liver. It is still
nous nephropathy follows a notoriously variable and often not clear how the complement abnormality induces the
indolent course. Overall, although proteinuria persists in glomerular changes.
greater than 60% of patients with membranous nephropa-
thy, only about 40% suffer progressive disease terminating MORPHOLOGY
in renal failure after 2 to 20 years. An additional 10% to
30% have a more benign course with partial or complete By light microscopy, type I MPGN and many cases of dense
remission of proteinuria. deposit disease are similar. The glomeruli are large, with an
accentuated lobular appearance, and show prolifera-
tion of mesangial and endothelial cells as well as infil-
trating leukocytes (Fig. 13–9, A). 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 “split-
ting” of the GBM is due to extension of processes of
mesangial and inflammatory cells into the peripheral capillary
loops and deposition of mesangial matrix (Fig. 13–9, B).
