Page 539 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster
P. 539
A Glomerular Diseases 525
Podocyte with effaced nephrotic syndrome. FSGS may be primary (idiopathic) or
foot processes secondary to one of the following conditions:
• In association with other conditions, such as HIV
infection (HIV nephropathy) or heroin abuse (heroin
nephropathy)
• As a secondary event in other forms of GN (e.g., IgA
nephropathy)
• As a maladaptation to nephron loss (as described earlier)
• In inherited or congenital forms. Autosomal dominant
forms are associated with mutations in cytoskeletal pro-
teins and podocin, both of which are required for the
integrity of podocytes. In addition, a sequence variant
in the apolipoprotein L1 gene (APOL1) on chromosome
22 appears to be strongly associated with an increased
risk of FSGS and renal failure in individuals of African
descent.
Primary FSGS accounts for approximately 20% to 30% of
all cases of the nephrotic syndrome. It is an increasingly
common cause of nephrotic syndrome in adults and
remains a frequent cause in children.
Normal PAT H O G E N E S I S
basement
membrane The pathogenesis of primary FSGS is unknown. Some inves-
tigators have suggested that FSGS and minimal-change disease
B are part of a continuum and that minimal-change disease
may transform into FSGS. Others believe them to be
Figure 13–6 Minimal-change disease. A, Under the light microscope distinct clinicopathologic entities from the outset. In any case,
the silver methenamine–stained glomerulus appears normal, with a deli- injury to the podocytes is thought to represent the
cate basement membrane. B, Schematic diagram illustrating diffuse initiating event of primary FSGS. As with minimal-
effacement of foot processes of podocytes with no immune deposits. change disease, permeability-increasing factors produced by
lymphocytes have been proposed. The deposition of hyaline
confined to the smaller plasma proteins, chiefly albumin masses in the glomeruli represents the entrapment of plasma
(selective proteinuria). The prognosis for children with this proteins and lipids in foci of injury where sclerosis develops.
disorder is good. More than 90% of children respond to a IgM and complement proteins commonly seen in the lesion
short course of corticosteroid therapy; however, proteinuria are also believed to result from nonspecific entrapment in
recurs in more than two thirds of the initial responders, damaged glomeruli. The recurrence of proteinuria and sub-
some of whom become steroid-dependent. Less than 5% sequent FSGS in a renal transplant in some patients who had
develop chronic kidney disease after 25 years, and it is FSGS, sometimes within 24 hours of transplantation, sup-
likely that most persons in this subgroup had nephrotic ports the idea that a circulating mediator is the cause of the
syndrome caused by focal and segmental glomerulosclero- podocyte damage in some cases.
sis not detected by biopsy. Because of its responsiveness
to therapy in children, minimal-change disease must be MORPHOLOGY
differentiated from other causes of the nephrotic syndrome
in nonresponders. Adults with this disease also respond to In FSGS, the disease first affects only some of the glomeruli
steroid therapy, but the response is slower and relapses are (hence the term focal) and, in the case of primary FSGS,
more common. initially only the juxtamedullary glomeruli. With progression,
eventually all levels of the cortex are affected. On histologic
Focal Segmental Glomerulosclerosis examination, FSGS is characterized by lesions occurring in
some tufts within a glomerulus and sparing of the others
Focal segmental glomerulosclerosis (FSGS) is character- (hence the term segmental). Thus, the involvement is
ized histologically by sclerosis affecting some but not both focal and segmental (Fig. 13–7). The affected glomeruli
all glomeruli (focal involvement) and involving only exhibit increased mesangial matrix, obliterated
segments of each affected glomerulus (segmental involve- capillary lumina, and deposition of hyaline masses
ment). This histologic picture often is associated with the (hyalinosis) and lipid droplets. In affected glomeruli,
immunofluorescence microscopy often reveals nonspecific
trapping of immunoglobulins, usually IgM, and complement
