Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor
UNLABELLED We report our experience of transplantation using Ahmedabad Tolerance Induction Protocol (ATIP) in primary focal segmental glomerulosclerosis (FSGS) known to recur leading to graft loss. METHODS Twenty-four primary FSGS patients were transplanted at our centre from 1997 to 2007. The 15 ATIP patients using hematopoietic stem cell transplantation (HSCT) under minimum nonmyeloablative conditioning was performed using living donors. Recipient mean age was 28 years and mean follow-up is 4.4 years. In contrast, nine control subjects of mean age 36 years had 4.8-year follow-up and received standard immunosuppression. Our Institutional Ethics Committee approved ATIP. Donor-recipient HLA match was similar. RESULTS Mean serum creatinine (SCr) values of the 12 ATIP patients who were doing well at 1, 3, 5 years and at present were: 1.62, 1.48, 1.6, and 1.92 mg%, respectively, on cyclosporine (1.5 +/- 1 mg/kg per day) and prednisone (7.5 mg/day). No recurrence was observed. One patient died at 19 months posttransplant following relentless acute rejection; two patients with unrelated grafts were lost due to acute rejection at 11 weeks and 2 years posttransplant. Two graft biopsies performed at 1 and 2 years posttransplant revealed unremarkable histology, seven showed acute CsA toxicity at 1 year posttransplant. No chronic changes were noted. Among control group B, with 5 of 9 functioning grafts, two were obtained from deceased and three from unrelated donors with mean SCr values at 1, 3, and 4 years as well as present, were 1.77, 1.65, 1.6, and 1.53 mg%, respectively. Four patients displayed recurrences at 8 days, 1 month, and 1 and 2 years posttransplant. One patient died at 1 year posttransplant; one patient received a subsequent cadaver donor graft and two are on maintenance dialysis. CONCLUSION Transplantation under ATIP seemed to mitigate recurrence of primary FSGS.