Page 685 - Textbook of Pathology, 6th Edition

minimal amounts of high molecular weight proteins such as 669
α2-macroglobulin. The basis for selective proteinuria appears
to be as under:
i) Reduction of normal negative charge on GBM (page 650)
due to loss of heparan sulfate proteoglycan from the GBM.
ii) Change in the shape of epithelial cells producing foot
process flattening due to reduction of sialoglycoprotein cell
coat.
Adults having MCD, however, have non-selective protein-
uria, suggesting more extensive membrane permeability
defect.

MORPHOLOGIC FEATURES. Grossly, the kidneys are
of normal size and shape.
By light microscopy, the findings are as under
(Fig. 22.16,A):
i) Glomeruli—The most characteristic feature is no
apparent abnormality in the glomeruli except for slight
Figure 22.15 RPGN, diagrammatic representation of ultrastructure increase in the mesangial matrix at the most (minimal
of a portion of glomerular lobule showing epithelial crescent formation change disease or nil lesion).
and subepithelial granular deposits.
ii) Tubules—There is presence of fine lipid vacuolation
and hyaline droplets in the cells of proximal convoluted
Minimal Change Disease tubules and, hence, the older name of the condition as
(Synonyms: MCD, Lipoid Nephrosis, Foot Process ‘lipoid nephrosis’.
Disease, Nil Deposit Disease)
iii) Interstitium—There may be oedema of the CHAPTER 22
Minimal change disease (MCD) is a condition in which the interstitium.
nephrotic syndrome is accompanied by no apparent change iv) Vessels—Blood vessels do not show any significant
in glomeruli by light microscopy. Its other synonyms, lipoid change.
nephrosis and foot process disease, are descriptive terms for
fatty changes in the tubules and electron microscopic By electron microscopy, the most characteristic feature of
appearance of flattened podocytes respectively. Minimal the disease is identified which is diffuse flattening of foot
change disease accounts for 80% cases of nephrotic syndrome processes of the visceral epithelial cells (podocytes) and,
in children under 16 years of age with preponderance in boys hence, the name foot process disease or podocytopathy
(ratio of boys to girls 2:1). In fact, historically, lipoid nephrosis (Fig. 22.16,B). Unlike other forms of GN, no deposits are
was the first condition associated with nephrotic sndrome. seen and the GBM is normal.
By immunofluorescence microscopy, no deposits of
ETIOPATHOGENESIS. The etiology of MCD remain complement or immunoglobulins are recognised (nil
elusive. However, following two groups have been deposit disease).
identified: The Kidney and Lower Urinary Tract
i) Idiopathic (majority of cases). CLINICAL FEATURES. The classical presentation of MCD
ii) Cases associated with systemic diseases (Hodgkin’s is of fully-developed nephrotic syndrome with massive and
disease, HIV infection) and drug therapy (e.g. NSAIDs, highly selective proteinuria, but hypertension is unusual. Most
rifampicin, interferon-α). frequently, the patients are children under 16 years (peak
incidence at 6-8 years of age).
The following features point to possible immunologic The onset may be preceded by an upper respiratory
pathogenesis for MCD: infection, atopic allergy or immunisation.
i) Absence of deposits by immunofluorescence microscopy. The disease characteristically responds to steroid therapy.
ii) Normal circulating levels of complement but presence In spite of remissions and relapses, long-term prognosis is
of circulating immune complexes in many cases. very good and most children become free of albuminuria
iii) Universal satisfactory response to steroid therapy. after several years.
iv) Evidence of increased suppressor T cell activity with
elaboration of cytokines (interleukin-8, tumour necrosis Membranous Glomerulonephritis
factor) which probably cause foot process flattening and (Synonym: Epimembranous Nephropathy)
altered charge on the GBM. Membranous GN is characterised by widespread thickening
v) Detection of a mutation in nephrin gene in cases of of the glomerular capillary wall and is the most common
congenital MCD has focused attention on genetic basis. cause of nephrotic syndrome in adults. In majority of cases
Nephrotic syndrome in MCD in children is characterised (85%), membranous GN is truly idiopathic, while in about
by selective proteinuria containing mainly albumin, and 15% of cases it is secondary to an underlying condition (e.g.