A Case of Posttransplant Recurrence of Focal Segmental Glomerulosclerosis with Donor-derived Immunoglobulin A Nephropathy and Banff IIA Acute Cell-mediated Rejection: A Therapeutic Challenge

Abstract

Primary focal segmental glomerulosclerosis (FSGS) recurrence varies between 10% and 60% and is an important predictor of graft survival. Here, we report the case with a combination of recurrence of FSGS, acute cell-mediated rejection, and donor-derived immunoglobulin A (IgA) nephropathy which required treatment with plasmapheresis and antithymocyte globulin. This patient is an 18-year-old female whose native kidney disease was a biopsy-proven FSGS and underwent ABO compatible live-related renal transplant with her mother as a donor. No induction agents were given and the patient was put on triple immunosuppression with Calcineurin inhibitors (CNIs), Mycophenolate mofetil (MMF), and steroids. On postoperative Day 2, the patient developed nephrotic range proteinuria. A transplant kidney biopsy was done. Biopsy revealed acute cell-mediated rejection, Banff II A with i3, t3, ptc1, v1, and C4d negative. There was also an increase in mesangial cellularity with IgA 3+ and C3 1+ on immunofluorescence which is IgA nephropathy, likely donor derived. Electron microscopy revealed significant effacement of podocytes. CNI levels are adequate. Pulse methylprednisolone 5 doses given. The patient was given two sessions of plasmapheresis with albumin and a single dose of rabbit antithymocyte globulin (ATG) 1.5 mg/kg was given. Plasmapheresis was withheld in view of studies reporting the removal of ATG following plasmapheresis. There was a gradual worsening of renal function with peak serum creatinine of 9 mg/dL which required three sessions of hemodialysis. The second renal biopsy on Day 13 showed features of acute tubular injury with borderline changes suspicious of acute cell mediated rejection (ACMR)–i1, t1. Currently, the patient is on regular follow-up with normal renal function with urine polymerase chain reaction of 0.4. We report this case which presented with a puzzling combination of ACMR, possible recurrence of native disease, and likely donor-derived IgA nephropathy that provided us with challenges in management. Treatment protocols with optimal dosing strategies and assessing response to treatment in these situations are still unclear due to the lack of large randomized trials.