Abstract
Background
Children with non-genetic steroid-resistant nephrotic syndrome (SRNS) are at high risk of disease recurrence (DR) and graft loss following renal transplant (RT). Although pre-emptive plasma exchange (PE) and rituximab have been suggested to prevent DR, there is insufficient published data to support this practice. The aim is to study the role of pre-emptive PE and rituximab in the prevention of DR in children with non-genetic SRNS undergoing living donor (LD) RT.
Methods
Prospective single-centre study of four consecutive children (age 6–17 years) with non-genetic SRNS (including two with previous graft loss due to DR) who underwent LD RT between July 2014 and September 2016. All patients received a single dose of rituximab 375 mg/m2 2–4 weeks prior to the RT and four sessions of PE in the week prior to RT. All patients had previously undergone bilateral native nephrectomies.
Results
All children had early DR (2–26 days) following LD RT. Following early initiation of PE, three children achieved partial remission (PR) or complete remission (CR) 5–22 days after commencing treatment. One child continued to have heavy proteinuria along with graft dysfunction despite 52 sessions of PE and lost the graft 5 months after RT. At the latest follow-up of 36–60 months following RT, one child remains in CR and two are in PR. The latest eGFR was 45–104 ml/min/1.73m2.
Conclusions
Pre-emptive rituximab and PE does not prevent DR in high-risk non-genetic SRNS. Prompt initiation of PE following DR appears to achieve PR or CR in the majority of patients.
Similar content being viewed by others
References
Bierzynska A, Saleem MA (2018) Deriving and understanding the risk of post-transplant recurrence of nephrotic syndrome in the light of current molecular and genetic advances. Pediatr Nephrol 33(11):2027–2035
Jungraithmayr TC, Hofer K, Cochat P, Chernin G, Cortina G, Fargue S, Grimm P, Knueppel T, Kowarsch A, Neuhaus T, Pagel P, Pfeiffer KP, Schäfer F, Schönermarck U, Seeman T, Toenshoff B, Weber S, Winn MP, Zschocke J, Zimmerhackl LB (2011) Screening for NPHS2 mutations may help predict FSGS recurrence after transplantation. J Am Soc Nephrol 22(3):579–585
Weber S, Gribouval O, Esquivel EL, Morinière V, Tête MJ, Legendre C, Niaudet P, Antignac C (2004) NPHS2 mutation analysis shows genetic heterogeneity of steroid resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int 66(2):571–579
Tejani A, Stablein DH (1992) Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the north American pediatric renal transplant co-operative study. J Am Soc Nephrol 2(12 suppl):S258–S263
Ding WY, Koziell A, McCarthy HJ (2014) Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence. J Am Soc Nephrol 25(6):1342–1348
Pelletier JH, Kumar KR, Engen R, Bensimhon A, Varner JD, Rheault MN, Srivastava T, Straatmann C, Silva C, Davis TK, Wenderfer SE, Gibson K, Selewski D, Barcia J, Weng P, Licht C, Jawa N, Kallash M, Foreman JW, Wigfall DR, Chua AN, Chambers E, Hornik CP, Brewer ED, Nagaraj SK, Greenbaum LA, Gbadegesin RA (2018) Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings. Pediatr Nephrol 33(10):1773–1780
Gohh RY, Yango AF, Morrissey PE, Monaco AP, Gautam A, Sharma M, McCarthy ET, Savin VJ (2005) Pre-emptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients. Am J Transplant 5(12):2907–2912
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 focal segmental glomerulosclerosis in children. Transplantation 71(5):628–633
Gonzalez E, Ettenger R, Rianthavorn P, Tsai E, Malekzadeh M (2011) Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation. Pediatr Transplant 15(5):495–501
Audard V, Kamar N, Sahali D, Cardeau-Desangles I, Homs S, Remy P, Aouizerate J, Matignon M, Rostaing L, Lang P, Grimbert P (2012) Rituximab therapy prevents focal and segmental glomerulosclerosis recurrence after a second renal transplantation. Transpl Int 25(5):e62–6
Park HS, Hong Y, Sun IO, Chung BH, Kim HW, Choi BS, Park CW, Jin DC, Kim YS, Yang CW (2014) Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult transplant recipients. Korean J Intern Med 29(4):482–488
Chikamoto H, Hattori M, Kuroda N, Kajiho Y, Matsumura H, Fujii H, Ishizuka K, Hisano M, Akioka Y, Nozu K, Kaito H, Shimizu M (2012) Pretransplantation combined therapy with plasmapheresis and rituximab in a second living-related kidney transplant pediatric recipient with a very high risk for focal segmental glomerulosclerosis recurrence. Pediatr Transplant 16(7):E286–E290
Bierzynska A, McCarthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, Nabhan MM, Kerecuk L, Hegde S, Hughes D, Marks S, Feather S, Jones C, Webb NJ, Ognjanovic M, Christian M, Gilbert RD, Sinha MD, Lord GM, Simpson M, Koziell AB, Welsh GI, Saleem MA (2017) Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 91(4):937–947
Grenda R, Watson A, Trompeter R, Tönshoff B, Jaray J, Fitzpatrick M, Murer L, Vondrak K, Maxwell H, van Damme-Lombaerts R, Loirat C, Mor E, Cochat P, Milford DV, Brown M, Webb NJ (2010) A randomised trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study. Am J Transplant 10(4):828–836
Schwartz GJ, Haycock GB, Edelman CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 51:875–878
Bierzynska A, Saleem MA (2017) Recent advances in understanding and treating nephrotic syndrome. F1000Res 6:121
Verghese PS, Rheault MN, Jackson S, Matas AJ, Chinnakotla S, Chavers B (2018) The effect of peritransplant plasmapheresis in the prevention of recurrent FSGS. Pediatr Transplant 22(3):e13154
Francis A, Trnka P, McTaggart SJ (2016) Long-term outcome of kidney transplantation in recipients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 11(11):2041–2046
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Shenoy, M., Lennon, R., Plant, N. et al. Pre-emptive rituximab and plasma exchange does not prevent disease recurrence following living donor renal transplantation in high-risk idiopathic SRNS. Pediatr Nephrol 35, 1081–1084 (2020). https://doi.org/10.1007/s00467-020-04500-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-020-04500-y