Page 953 - Clinical Immunology_ Principles and Practice ( PDFDrive )

920 Part Seven Organ-Specific Inflammatory Disease

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FIG 68.4 Focal Segmental Glomerulosclerosis (FSGS). Several forms of glomerular lesions
are seen in FSGS, often within the same biopsy: A, minimal abnormality (periodic acid–Schiff
[PAS] stain); B, tip lesion manifested by segmental glomerular tuft lesion near the origin of the
proximal tubule (PAS stain); C, classical perihilar lesion (PAS stain); and D, collapsing glomerulopathy;
the glomerulus is globally contracted with wrinkling of the basement membranes; this is associated
with hyperplasia of podocytes surrounding the glomerular capillaries (methenamine silver stain).

cyclophosphamide, calcineurin inhibitors, or mycophenolate. KeY COnCePtS
There are mixed outcomes with use of rituximab for FSGS, but
it appears less effective for steroid resistant cases. 9,10 Complete Membranous Nephropathy (MN)
remission of proteinuria is less commonly achieved in FSGS • Common cause of idiopathic nephrotic syndrome in adults
than in MCD. Relapses of the disease and progression to end-stage • Autoantibodies to phospholipase A 2 receptor (PLA 2 R) detected in large
kidney disease (ESKD) remains a major concern despite immu- percentage of patients with primary MN
nosuppression, particularly in steroid-resistant and frequently • Several secondary causes: systemic lupus erythematosus (SLE), drugs,
relapsing patients. Several novel therapies that target various chronic hepatitis, certain malignancies
immunological, inflammatory, and costimulatory pathways (i.e., • One-quarter of patients have spontaneous remission
blockade of CD 80 with cytotoxic T lymphocyte antigen 4-Ig • One-quarter of patients develop end-stage renal disease within a
decade
(CTLA-4-Ig) are currently under investigation for FSGS. 11,12 • Protracted nephrotic syndrome confers risks of cardiovascular and
thromboembolic events
MEMBRANOUS NEPHROPATHY • Therapies: steroids, alkylating agents, calcineurin inhibitors, rituximab,
lipid-lowering drugs, angiotensin antagonists
MN is identified in approximately 20% of adults who undergo
renal biopsy for nephrotic syndrome. It is a less frequent cause
of nephrotic syndrome in children. Primary MN is usually a Etiology and Pathogenesis
diagnosis of exclusion after considering secondary causes, such MN is characterized by subepithelial (epimembranous) immune
as medication reactions, infections, neoplasms, and systemic deposits containing IgG and complement components. The
illnesses (i.e., SLE) leading hypothesis based on experimental models is that immune