Focal segmental glomerulosclerosis - Pathogenesis clinical manifestation and treatment

Focal segmental glomerulosclerosis (FSGS) is a clinicopathological entity of not fully explained etiology characterized by focal and segmental occurrence of lesions. It is currently believed that primary FSGS is caused by alterations in glomerular epithelial cells (podocytes). FSGS is one of the most frequent causes of nephrotic syndrome in adults. The course of the disease is strongly influenced by proteinuria or nephrotic syndrome and renal insufficiency at presentation. The prognosis of FSGS is poor because there are no spontaneous remissions and because of resistance to treatment. FSGS has a high recurrence rate after kidney transplantation with loss of graft function in half of affected individuals. The efficacy of treatment of FSGS depends on histopathological findings in renal biopsy and clinical presentation, especially on the intensity of proteinuria. There is no uniform standard of therapy for FSGS. A six-month course of steroids and/or cyclosporine A (CsA) as well as ACE inhibitors and/or angiotensin receptor blockers (ARBs) and lipid-lowering agents are recommended. In steroid-dependent patients or those with frequent relapse of proteinuria, cyclophosphamide with prednisone should be administered. In steroid-resistant nephrotic syndrome the podocine gene mutation (NPHS2 gene) should be assessed to avoid prolonged and ineffective treatment with adverse effects and evaluation before further kidney allograft transplantation, with a low risk of recurrence in homozygous mutation patients (Adv Clin Exp Med 2008, 17, 2, 221-226).