title: A prospective, open-label trial of sirolimus in the treatment of focal segmental glomerulosclerosis.
abstract: Calcineurin inhibitors are effective therapy for steroid-resistant focal segmental glomerulosclerosis (FSGS) but are associated with significant morbidity and nephrotoxicity. Sirolimus is a novel immunosuppressive agent that is structurally related to tacrolimus but demonstrates no long-term nephrotoxicity. For determination of the efficacy of sirolimus in reducing proteinuria, a prospective, open-label trial was conducted of 21 patients with idiopathic, steroid-resistant FSGS. A complete response was defined as <300 mg protein/24 h after 6 mo, whereas a partial response was defined as a 50% reduction in baseline proteinuria. After 6 mo of therapy, sirolimus induced complete remission in four (19%) of 21 patients and partial remissions in eight (38%). Among sirolimus-responsive patients, 6 mo of therapy decreased proteinuria from a mean of 8.8 +/- 1.7 to 2.1 +/- 0.5 g/24 h (P = 0.0003). In responsive patients, GFR was maintained (45 +/- 6 versus 47 +/- 7 ml/min per 1.73 m2 at 6 mo) throughout the study, whereas nonresponders tended to decrease (31 +/- 4 versus 28 +/- 5 ml/min per 1.73 m2). Using dextran sieving analysis, complete or partial response was associated with an increase in the glomerular ultrafiltration coefficient (K(f), 7 +/- 1. versus 8 +/- 0.9 units at 6 mo; P < 0.05). Glomerular permselectivity and K(f) tended to decrease in nonresponders (8.2 +/- 1.9 versus 6.2 +/- 1.3 units at 6 mo; P = 0.07). Patients with complete remission had a higher GFR (45 +/- 6 versus 31 +/- 4 ml/min per 1.73 m2) at the end of 6 mo compared with nonresponders. In patients with steroid-resistant FSGS, sirolimus reduced proteinuria and glomerular pore size and increased K(f) in patients with steroid-resistant FSGS.
authors: Department of Medicine, Division of Nephrology, Emory University School Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA. jtumlin@emory.edu
authors: James A
authors: JA
authors: Tumlin
authors: Danlyn
authors: D
authors: Miller
authors: Mitzi
authors: M
authors: Near
authors: Sasi
authors: S
authors: Selvaraj
authors: Randolph
authors: R
authors: Hennigar
authors: Antonio
authors: A
authors: Guasch
mesh_terms: D000328:Adult; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus