Tacrolimus and Plasmapheresis in Treatment-Resistant FSGS

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DESCRIPTION (provided by applicant): Focal segmental glomerulosclerosis (FSGS) is observed in 10-20% of children and 5% of adults with idiopathic nephrotic syndrome, and in 15% of children and 5% of adults with end-stage renal disease (ESRD). A significant number of patients with FSGS do not respond to corticosteroid therapy and the results of other therapeutic regimens have been disappointing. No evidence-based treatment guidelines exist for steroid- resistant patients because of the lack of well-controlled prospective studies and the small number of patients included in most reports. In 2003, NIDDK initiated a multicenter, prospective randomized, clinical trial (FSGS-CT) that will compare the effectiveness of cyclosporin A to a regimen of mycophenolate mofetil and oral pulse steroids in inducing clinical remission in patients with steroid-resistant FSGS. The recruitment for the study, which will include 500 patients, started in 2004 and will continue through the end of January 2008. Very limited therapeutic options exist in patients who fail to respond to either of the two treatment regimes of FSGS-CT. The aim of the proposed FSGS-CT ancillary study is to compare the effectiveness of tacrolimus with tacrolimus plus plasmapheresis in inducing clinical remission in patients who fail to respond to either of the two treatment regimens of FSGS-CT. This prospective pilot study will include 50 patients, who will be randomized into two groups of 25 patients each. Patients in both groups (Group 1 and II) will receive tacrolimus as well as angiotensin converting enzyme inhibitor or an angiotensin receptor blocker for a period of 6 months. Those in Group 2 will also receive 15 sessions of plasmapheresis over initial 6-week period. The primary endpoint is the number of patients in remission at the end of the study at 26 weeks. This study proposal, which is being submitted on behalf of the Midwest Pediatric Nephrology Consortium, has been approved by the Ancillary Studies Committee of the FSGS-CT, and is awaiting final approval by the FSGS-CT Steering Committee. The diagnosis of FSGS is associated with a sense of helplessness because of its poor response to the currently used medications, progression to chronic renal failure in a significant number of patients, and a high risk of recurrence in transplanted kidneys. The proposed study will offer new treatment options in such patients and save many from the pain and the distress of undergoing dialysis and renal transplantation.