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. 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): isotretinoin for immunotherapy-resistant patients with FSGS (N=5) and plasma exchange plus cyclophosphamide (N12) and rituximab + cyclosporine. We are carrying out a trial of rituximab (one or two courses) combined with cyclosporine, in an open label trial recruiting patients with treatment-refractory FSGS. We have recruited 12 patients. Responses have included complete remission, partial remission, and no response. We are participating in the Genzyme-sponsored, multi-center trial of fresolimumab (anti-TGFbeta ab) for primary FSGS.

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Sharma, Kumar; Karl, Bethany; Mathew, Anna V et al. (2013) Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol 24:1901-12
Joy, Melanie S; Gipson, Debbie S; Dike, Mary et al. (2009) Phase I trial of rosiglitazone in FSGS: I. Report of the FONT Study Group. Clin J Am Soc Nephrol 4:39-47