Focal Sclerosing Glomerulosclerosis

FOCAL SCLEROSING GLOMERULOSCLEROSIS

Focal glomerulosclerosis or focal segmental glomerulosclerosis (FSGS) is a common cause of idiopathic nephrotic syndrome in adults, accounting for about 35 percent of all cases. About 50 percent of all FSGS cases appear to afflict black people, suggest-ing possible involvement of their genetic background and socioeconomic status. FSGS is classified as primary or second-ary. Primary or idiopathic FSGS usually presents with overt nephrotic syndrome. Secondary FSGS presents with nonne-phrotic-range proteinuria (<3.5 g/day) and renal dysfunction. The latter form has been considered to be a physiologic response to hyperfiltration or glomerular hypertro-phy as a result of nephron loss. This loss can be seen in unilateral nephrectomy, unilateral agenesis of one kidney, reflux nephropathy, renal vasodilation, obesity, and preeclampsia. Secondary FSGS may be seen as a response to a prior injury of any cause (e.g., acute glomerulonephritis, or vasculitis). The transforming growth fac-tor–beta (TGF-β), which is released from affected glomerular cells and platelets, appears to contribute to the development of glomerulosclerosis. TGF-β promotes extracellular matrix production, prevents matrix degradation, and facilitates migra-tion and adhesion of inflammatory cells to the matrix. In experimental animals, inhi-bition of TGF-β with use of antibodies or inhibitors appears to decrease or abrogate glomerular scarring.

FSGS is diagnosed with a kidney biopsy. On light microscopy, some of the glomeruli show segmental areas of mesangial collapse and sclerosis. There is minimal mesangial hypercellularity. No immune deposits can be found except for nonspecific binding of IgM and complements in sclerotic lesions. Like MCD, there is diffuse fusion of the epithelial foot processes. The histologic similarities between FSGS and MCD have led many investigators to believe that the former may be a more severe form of the latter. Like MCD, a circulating toxin has been identified from the serum of FSGS patients that can increase permeability of isolated glomeruli to albumin. This toxin (or cytokine) appears to cause injury to the podocytes similar to the GPF found in MCD. This finding is also supported by rapid recurrence of FSGS in kidney trans-plant patients.

Primary FSGS can cause progressive renal disease if not treated aggressively. Like MCD, primary FSGS will respond to steroids and immunosuppressive agents, albeit it entails a more prolonged therapy. The degree of proteinuria is an important prognostic factor. Patients with nonne-phrotic proteinuria have better survival rates that those with nephrotic-range pro-teinuria. Poor prognostic factors include advanced renal insufficiency at the out-set of treatment and presence of intersti-tial fibrosis on the biopsy. Treatment of secondary FSGS is directed to modify-ing the underlying primary disease (e.g., antiviral therapy for HIV-associated nephropathy). In both types of FSGS, use of ACE inhibitors and ARBs are used for their antiproteinuric properties and renoprotective potentials.