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Published on: October 11, 2014
Recurrent focal glomerulosclerosis in pediatric renal allografts: the Miami experience
Hans Hubsch1, Brenda Montané, Carolyn Abitbol
1Division of Pediatric Nephrology, Holtz Children's Hospital, University of Miami, P.O. Box 016960 (M-714), Miami, FL 33101, USA.
Abstract:
Recurrence of focal glomerulosclerosis (FSGS) following renal transplantation is a common cause of allograft loss and clinical morbidity. Recent attempts to control proteinuria and morbidity with plasmapheresis (PP) have met with limited success. Our experience with the use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the management of refractory FSGS pre transplant suggested its potential benefit in post-transplant recurrence. This report presents our 25-year experience in pediatric renal transplantation of patients with FSGS divided into two treatment eras: Era 1-prior to use of daclizumab (anti-IL-2R) and Era 2-after daclizumab. A total of 179 pediatric patients were transplanted during the 25-year period. FSGS was confirmed in 27 (15%); 16 of 28 allografts (57%) had recurrence of FSGS during the post-transplant period. In Era 1, only 6 of 16 (38%) recurred in the allograft, while 10 of 12 (83%) recurred during Era 2. The odds ratio of recurrence of FSGS in the allograft after induction with anti-IL-2R was 8.3 (95% confidence interval=1.3-52, P =0.02). Only 2 patients in Era 1 received PP, while 10 in Era 2 were entered into an intensive PP protocol followed by maintenance with AB consisting of angiotensin receptor blockers alone, or in combination with angiotensin-converting enzyme inhibitor. Although proteinuria decreased an average of 80+/-16% with PP, the response was variable and severe morbid edema persisted in poor responders. Maximum benefit occurred with the addition of AB and MMF. After a follow-up of 27+/-15 months, proteinuria has shown a sustained decrease of 94+/-8% below baseline. In conclusion, our experience suggests that, with recurrent FSGS, a limited course of PP followed by maintenance therapy with AB and MMF improves symptoms and may preserve allograft function.
Insights
Recurrence of focal glomerulosclerosis (FSGS) after kidney transplant is common. Combining plasmapheresis with angiotensin blockade and mycophenolate mofetil offers improved outcomes for managing FSGS recurrence.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pediatric Nephrology
Background:
- Recurrence of focal glomerulosclerosis (FSGS) post-renal transplantation leads to graft loss and morbidity.
- Previous treatments like plasmapheresis (PP) showed limited success in managing FSGS recurrence.
- Pre-transplant use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) suggested potential benefits for post-transplant FSGS.
Purpose of the Study:
- To evaluate the 25-year experience with pediatric renal transplantation for FSGS.
- To compare outcomes between two treatment eras: pre- and post-daclizumab (anti-IL-2R) induction.
- To assess the efficacy of plasmapheresis, angiotensin blockade, and mycophenolate mofetil in managing recurrent FSGS.
Main Methods:
- Retrospective analysis of 179 pediatric renal transplant recipients over 25 years.
- Patients divided into Era 1 (prior to daclizumab) and Era 2 (post-daclizumab).
- Treatment protocols included plasmapheresis, angiotensin blockade (ARBs +/- ACE inhibitors), and MMF for recurrent FSGS.
Main Results:
- FSGS recurrence occurred in 57% of allografts, with significantly higher rates in Era 2 (83%) vs. Era 1 (38%).
- Odds of recurrence increased 8.3-fold with anti-IL-2R induction (P=0.02).
- Combination therapy (PP, AB, MMF) led to a sustained 94% decrease in proteinuria post-transplant.
Conclusions:
- Daclizumab induction is associated with increased FSGS recurrence risk in pediatric renal transplantation.
- A limited course of plasmapheresis followed by maintenance therapy with angiotensin blockade and MMF improves symptoms.
- This combined therapeutic approach may help preserve allograft function in patients with recurrent FSGS.
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