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.
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Dall’Amico R, Ghiggeri G, Carraro M, Artero M, Ghio L, Zamorani E, Zennaro C, Basile G, Montini G, Rivabella L, Cardillo M, Scalamogna M, Ginevri F (1999) Prediction and treatment of recurrent FSGS after renal transplantation in children. Am J Kidney Dis 34:1048–1055
Benfield M, McDonald R, Sullivan E, Stablein D, Tejani A (1999) The 1997 annual renal transplantation in children: Report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 3:152–167
Sharma M, Sharma R, McCarthy E, Savin V (1999) “The FSGS factor”: enrichment in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol 10:552–561
Savin V, Sharma R, Sharma M, McCarthy E, Swan U, Ellis E, Lovell H, Warady B, Gunwar R, Chonko A, Artero M, Vincenti F (1996) Circulating factor with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 334:878–883
Greenstein S, Delrio M, Ong E, Feuerstein D, Schechner R, Kim D, Corey H, Kaskel R, Tellis V, Moritz M (2000) Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts. Pediatr Nephrol 14:1061–1065
Ohta T, Kawaguchi H, Hattori M, Komatsu Y, Akioka Y, Nagata M, Shiraga H, Ito K, Takahashi K, Ishikawa N, Tanabe K, Yamaguchi Y, Ota K (2001) Effect of pre and postoperative plasmapheresis on posttransplant recurrence of FSGS in children. Transplantation 71:628–633
Belson A, Yorgin P, Al-Uzri A, Salvatierra O, Higgins J, Alexander S (2001) Long term plasmapheresis and protein A column treatment of recurrent FSGS. Pediatr Nephrol 16:985–989
Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G (2003) Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 18:772–777
Abitbol C, Burke G, Zilleruelo G, Montane B, Strauss J (1991) Clinical management of the pediatric renal-allograft recipient. Child Nephrol Urol 11:169–178
Ciancio G, Burke G, Suzart K, Mattiazzi A, Rosen A, Zilleruelo G, Abitbol C, Montane B, Miller J (2002) Effect of daclizumab, tacrolimus and mycophenolate mofetil in pediatric first renal transplant recipients. Transplant Proc 34:1944–1945
Ettenger R, Mentser M, Warshaw B (1999) The long-term use of mycophenolate mofetil in pediatric renal transplantation: a report of the pediatric mycophenolate mofetil study group. Transplantation 67:S118
International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564
Tarshish P, Tobin J, Bernstein J, Edelman C (1996) Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. Pediatr Nephrol 10:590–593
Abitbol C, Zilleruelo G, Freundlich M, Strauss J (1990) Quantification of proteinuria with urinary protein/creatinine ratios and random testing with dipsticks in nephrotic syndrome. J Pediatr 116:243–247
Motulsky H (1995) Intuitive biostatistics, 2nd edn. Oxford University Press, New York, pp 207–262
Raafat R, Travis L, Kalia A, Diven S (2000) Role of transplant induction therapy on recurrence rate of focal segmental glomerulosclerosis. Pediatr Nephrol 14:189–194
Sheth R, Kale A, Goldstein S, Brewer E (2001) Rapid recurrence of post-transplant FSGS in pediatric patients after daclizumab induction. Pediatr Nephrol 16:C190
Gagnadoux MF (2002) Does antibody induction therapy with daclizumab or basiliximab increase the risk of recurrence of post-transplant focal segmental glomerulosclerosis? Pediatr Nephrol 17:305
Grimbert P, Audard V, Remy P, Lang P, Sahali D (2003) Recent approaches to the pathogenesis of minimal-change nephrotic syndrome. Nephrol Dial Transplant 18:245–248
Baum M, Stablein D, Panzarino V, Tejani A, Harmon W, Alexander S (2001) Loss of living donor renal allograft survival advantage in children with focal segmental glomerulosclerosis. Kidney Int 59:328–333
Briggs W, Choi M, Scheel P (1998) Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 31:213–217
Fujihara C, De L, Malheiros I, Antunes G, Oliveira I, Zatz R (2000) Combined mycophenolate mofetil and losartan therapy arrests established injury in the remnant kidney. J Am Soc Nephrol 11:283–290
Stigant C, Cohen J, Vivera M, Zaltsman J (2000) ACE inhibitors and angiotensin II antagonist in renal transplantation: an analysis of safety and efficacy. Am J Kidney Dis 35:58–63
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This work was supported in part by a grant from Children’s Medical Services, Florida’s Department of Health.
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Hubsch, H., Montané, B., Abitbol, C. et al. Recurrent focal glomerulosclerosis in pediatric renal allografts: the Miami experience. Pediatr Nephrol 20, 210–216 (2005). https://doi.org/10.1007/s00467-004-1706-7
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DOI: https://doi.org/10.1007/s00467-004-1706-7