Focal segmental glomerulosclerosis: Treatment

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications & trials

Abstract

Focal segmental glomerulosclerosis (FSGS) is a clinical-pathologic syndromes characterized by the accumulation of fibrotic proteins in glomeruli, initially involving only some glomeruli (focal) and involving portions (segments) of the affected glomeruli. FSGS can be classified as follows: idiopathic FSGS, genetic FSGS and post-adaptive FSGS (associated with glomerular hypertrophy and hyperfiltration, and due to reduced renal mass, renal toxins, obesity, and sickle cell disease). A related syndrome is collapsing glomerulopathy, associated with podocyte hyperplasia whereas FSGS is associated with podocyte depletion. Collapsing glomerulopathy can be classified as HIV-associated or idiopathic.[unreadable] [unreadable] Many patients with podocyte diseases, including minimal change nephropathy (MCN), FSGS, and collapsing glomerulopathy are refractory to all conventional remittive therapy. We now have three open-label, phase 2 trials for podocyte diseases (current number enrolled given in parentheses): oral pulse dexamethasone for therapy-naove patients with FSGS and MCN (N=8), isotretinoin for immunotherapy-resistant patients with FSGS (N=5) and plasma exchange plus cyclophosphamide (N12).[unreadable] [unreadable] In the past year, a multi-center, randomized, double-blind, placebo controlled trial of pirfenidone in diabetic nephropathy that we participated in was completed and the results show a modest effect o of pirfenidone 1200 mg/d (but not pirfenidone 2400 mg/d) to slow loss of glomerular filtration rate over 1 year.[unreadable] [unreadable] We are nearing completion of our second open label, uncontrolled pilot trials of pulse oral dexamethasone for podocyte diseases, including minimal change nephropathy, FSGS, and collapsing glomerulopathy. The first trial (lower dose, 32 weeks) involved 14 patients, and the second trial (higher dose, 48 weeks) has enrolled 9 patients. Take together, these studies suggest that pulse oral dexamethasone is safe but only modestly effective.