A Prospective, Open-Label Trial of Sirolimus in the Treatment of Focal Segmental Glomerulosclerosis

[摘要] 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 (Kf, 7 ± 1. versus 8 ± 0.9 units at 6 mo; P < 0.05). Glomerular permselectivity and Kf 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 Kf in patients with steroid-resistant FSGS.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome