Focal Segmental Glomerulosclerosis (FSGS) Recurrence in Kidney Allograft Recipients

Abstract

Primary or idiopathic focal and segmental glomerulosclerosis (FSGS) accounts for approximately 10% and 20% of cases of idiopathic nephrotic syndrome in children and adults, respectively. The primary pathophysiologic process appears to be an injury of glomerular visceral epithelial cells, so-called podocytes, followed by an initial proliferation of mesangial, epithelial and endothelial cells with subsequent collapse of glomerular capillary loops and eventual sclerosis. The most popular pathogenetic hypothesis suggests the involvement of one or more circulating plasma factor(s), that appears to be protein between 30 and 50 kD molecular weight, altering glomerular permeability to proteins and causing proteinuria. Familial forms of FSGS occur due to mutations of several podocyte protein genes. FSGS can be a secondary process as well. Regardless of the etiology, the natural history of the disease include: peripheral edema, refractory proteinuria, hypertension, and progressive loss of renal function. FSGS frequently recurs after kidney transplantation with the recurrence rate of 30% after first transplantation, and 80% or more in the subsequent transplants. Risk factors of recurrence include a rapid progression of the primary disease to chronic kidney disease (CKD) stage 5, younger recipient age, early onset of nephrotic range proteinuria after kidney transplantation and frequent loss of the first and subsequent allografts. Considerable number of patients with recurrent FSGS respond to plasmapheresis (PP), especially if instituted early in the course of disease and before glomerulosclerosis has been established. Combined therapy with PP and cyclophosphamide may be beneficial. Other treatments consists of intravenous cyclosporine (CsA) and oral steroids. In some patients successful treatment of recurrent FSGS with the anti-CD20 monoclonal antibody, rituximab, in conjunction with PP has been reported. As a symptomatic treatment the use of ACE inhibitors should be recommended.