Page 542 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

528 C H A P T E R 13 Kidney and Its Collecting System

Type I MPGN

Subendothelial
deposit

Interposed
mesangial
cell process

A

Intramembranous
deposit

Dense Deposit Disease

B

Figure 13–9 A, Membranoproliferative glomerulonephritis (MPGN), showing mesangial cell proliferation, basement membrane thickening, leukocyte
infiltration, and accentuation of lobular architecture. B, Schematic representation of patterns in the two types of MPGN. In type I there are subendo-
thelial deposits; in type II, now called dense deposit disease, intramembranous characteristically dense deposits are seen. In both types, mesangial
interposition gives the appearance of split basement membranes when viewed by light microscopy.

Type I MPGN is characterized by discrete subendothe- recipients. MPGN type I may occur in association with
lial electron-dense deposits (Fig. 13–9, B). By immuno- other disorders (secondary MPGN), such as systemic lupus
fluorescence microscopy, C3 is deposited in an irregular erythematosus, hepatitis B and C, chronic liver disease, and
granular pattern, and IgG and early complement components chronic bacterial infections. Indeed, many so-called idio-
(C1q and C4) often are also present, indicative of an immune pathic cases are believed to be associated with hepatitis C
complex pathogenesis. and related cryoglobulinemia.

By contrast, in the aptly named dense deposit disease S U M M A RY
the lamina densa and the subendothelial space of the GBM The Nephrotic Syndrome
are transformed into an irregular, ribbon-like, extremely
electron-dense structure, resulting from the deposition of • The nephrotic syndrome is characterized by proteinuria,
material of unknown composition. C3 is present in irregular which results in hypoalbuminemia and edema.
chunky and segmental linear foci in the basement membranes
and in the mesangium. IgG and the early components of the • Podocyte injury is an underlying mechanism of proteinuria,
classical complement pathway (C1q and C4) are usually and may be the result of nonimmune causes (as in minimal-
absent. change disease and FSGS) or immune mechanisms (as in
membranous nephropathy).
Clinical Course
The principal mode of presentation (in approximately 50% • Minimal-change disease is the most frequent cause of
of cases) is the nephrotic syndrome, although MPGN or nephrotic syndrome in children; it is manifested by pro-
dense deposit disease may begin as acute nephritis or mild teinuria and effacement of glomerular foot processes
proteinuria. The prognosis of MPGN type I generally is without antibody deposits; the pathogenesis is unknown;
poor. In one study, none of the 60 patients followed for 1 the disease responds well to steroid therapy.
to 20 years showed complete remission. Forty percent pro-
gressed to end-stage renal failure, 30% had variable degrees • FSGS may be primary (podocyte injury by unknown mech-
of renal insufficiency, and the remaining 30% had persis- anisms) or secondary (e.g., as a consequence of previous
tent nephrotic syndrome without renal failure. Dense glomerulonephritis, hypertension, or infection such as
deposit disease carries an even worse prognosis, and it with HIV); glomeruli show focal and segmental oblitera-
tends to recur more frequently in renal transplant tion of capillary lumina, and loss of foot processes; the
disease often is resistant to therapy and may progress to
end-stage renal disease.