Recurrent focal segmental glomerulosclerosis: a discrete clinical entity

Abstract

Focal segmental glomerulosclerosis refers to a set of particular histopathologic lesions in which steroid-resistant podocyte injury leads to patchy adhesions between the glomerular tuft and Bowman's capsule, followed by progressive glomerulosclerosis and proteinuric renal failure. Because of the nonspecific nature of this lesion, it has been difficult to classify the various forms of primary nephrotic syndrome in children. However, with the recognition of hereditary FSGS caused by mutations podocyte slit diaphragm genes, it is increasingly clear that the steroid-resistant form of FSGS that recurs in the renal allografts (R-FSGS) constitutes a distinct clinical entity. Capitalizing on recent studies in which patients have been screened for slit diaphragm gene mutations, this review focuses on the natural history and pathogenesis of R-FSGS.

Figure 1

Immediate recurrence of FSGS (rFSGS) following deceased donor kidney transplantation. A 15-year-old girl with steroid-resistant FSGS had bilateral nephrectomy prior to transplantation. Proteinuria recurred within the first 12 hours but was controlled with intensive plasma exchange therapy (1.5 plasma volumes with albumin replacement). Efforts to wean plasmapheresis lead to a rise in urine protein/creatinine ratio (g/g) on several occasions. Each triangle represents a plasma exchange.

Figure 2

Plasmapheresis effluent from a patient with a recurrent FSGS disrupts the cytoskeleton of human podocytes in culture. Immortalized human podocytes (gift from Dr. Saleem) were incubated for 6 hours with 10% plasmapheresis effluent from a control patient undergoing plasmapheresis for a nonrenal disease (upper panel); PPE from a patient with recurrent FSGS collected at the start of procedure (middle panels, “early PPE”); end of plasmapheresis (lower panels, “late PPE”). The “early PPE,” but not the late PPE FSGS sample disrupts polymerized actin (phalliodin staining, red) and nonmuscle mysosin II (staining with anti-MYH9 antibody-green); arrowheads: actin stress fibers; scale bar 5 mc.