Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

Jonathan H. Pelletier, Karan R. Kumar, Rachel Engen, Adam Bensimhon, Jennifer D. Varner, Michelle N. Rheault, Tarak Srivastava, Caroline Straatmann, Cynthia Silva, T. Keefe Davis, Scott E. Wenderfer, Keisha Gibson, David Selewski, John Barcia, Patricia Weng, Christoph Licht, Natasha Jawa, Mahmoud Kallash, John W. Foreman, Delbert R. WigfallAnnabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Eileen D. Brewer, Shashi K. Nagaraj, Larry A. Greenbaum, Rasheed A. Gbadegesin*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

Original languageEnglish (US)
Pages (from-to)1773-1780
Number of pages8
JournalPediatric Nephrology
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Nephrotic Syndrome
Kidney Transplantation
Kidney
Biopsy
Recurrence
Lipoid Nephrosis
Focal Segmental Glomerulosclerosis
Steroids
Allografts
Pediatrics
Immunosuppression
Multicenter Studies
Chronic Kidney Failure
Histology
Adrenal Cortex Hormones
Transplantation
Logistic Models
Demography
Transplants

Keywords

  • Focal segmental glomerulosclerosis
  • Immunosuppression
  • Lipoid
  • Nephrosis
  • Nephrotic syndrome
  • Transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Pelletier, J. H., Kumar, K. R., Engen, R., Bensimhon, A., Varner, J. D., Rheault, M. N., ... Gbadegesin, R. A. (2018). Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings. Pediatric Nephrology, 33(10), 1773-1780. https://doi.org/10.1007/s00467-018-3994-3
Pelletier, Jonathan H. ; Kumar, Karan R. ; Engen, Rachel ; Bensimhon, Adam ; Varner, Jennifer D. ; Rheault, Michelle N. ; Srivastava, Tarak ; Straatmann, Caroline ; Silva, Cynthia ; Davis, T. Keefe ; Wenderfer, Scott E. ; Gibson, Keisha ; Selewski, David ; Barcia, John ; Weng, Patricia ; Licht, Christoph ; Jawa, Natasha ; Kallash, Mahmoud ; Foreman, John W. ; Wigfall, Delbert R. ; Chua, Annabelle N. ; Chambers, Eileen ; Hornik, Christoph P. ; Brewer, Eileen D. ; Nagaraj, Shashi K. ; Greenbaum, Larry A. ; Gbadegesin, Rasheed A. / Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings. In: Pediatric Nephrology. 2018 ; Vol. 33, No. 10. pp. 1773-1780.
@article{79377267a6d44aed92184ac0b45159a7,
title = "Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings",
abstract = "Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41{\%}) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78{\%} of patients with LSRNS compared to 39{\%} of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76{\%} recurrence rate compared with a 40{\%} recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95{\%} CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.",
keywords = "Focal segmental glomerulosclerosis, Immunosuppression, Lipoid, Nephrosis, Nephrotic syndrome, Transplantation",
author = "Pelletier, {Jonathan H.} and Kumar, {Karan R.} and Rachel Engen and Adam Bensimhon and Varner, {Jennifer D.} and Rheault, {Michelle N.} and Tarak Srivastava and Caroline Straatmann and Cynthia Silva and Davis, {T. Keefe} and Wenderfer, {Scott E.} and Keisha Gibson and David Selewski and John Barcia and Patricia Weng and Christoph Licht and Natasha Jawa and Mahmoud Kallash and Foreman, {John W.} and Wigfall, {Delbert R.} and Chua, {Annabelle N.} and Eileen Chambers and Hornik, {Christoph P.} and Brewer, {Eileen D.} and Nagaraj, {Shashi K.} and Greenbaum, {Larry A.} and Gbadegesin, {Rasheed A.}",
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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', Pediatric Nephrology, vol. 33, no. 10, pp. 1773-1780. https://doi.org/10.1007/s00467-018-3994-3

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings. / Pelletier, Jonathan H.; Kumar, Karan R.; Engen, Rachel; Bensimhon, Adam; Varner, Jennifer D.; Rheault, Michelle N.; Srivastava, Tarak; Straatmann, Caroline; Silva, Cynthia; Davis, T. Keefe; Wenderfer, Scott E.; Gibson, Keisha; Selewski, David; Barcia, John; Weng, Patricia; Licht, Christoph; Jawa, Natasha; Kallash, Mahmoud; Foreman, John W.; Wigfall, Delbert R.; Chua, Annabelle N.; Chambers, Eileen; Hornik, Christoph P.; Brewer, Eileen D.; Nagaraj, Shashi K.; Greenbaum, Larry A.; Gbadegesin, Rasheed A.

In: Pediatric Nephrology, Vol. 33, No. 10, 01.10.2018, p. 1773-1780.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

AU - Pelletier, Jonathan H.

AU - Kumar, Karan R.

AU - Engen, Rachel

AU - Bensimhon, Adam

AU - Varner, Jennifer D.

AU - Rheault, Michelle N.

AU - Srivastava, Tarak

AU - Straatmann, Caroline

AU - Silva, Cynthia

AU - Davis, T. Keefe

AU - Wenderfer, Scott E.

AU - Gibson, Keisha

AU - Selewski, David

AU - Barcia, John

AU - Weng, Patricia

AU - Licht, Christoph

AU - Jawa, Natasha

AU - Kallash, Mahmoud

AU - Foreman, John W.

AU - Wigfall, Delbert R.

AU - Chua, Annabelle N.

AU - Chambers, Eileen

AU - Hornik, Christoph P.

AU - Brewer, Eileen D.

AU - Nagaraj, Shashi K.

AU - Greenbaum, Larry A.

AU - Gbadegesin, Rasheed A.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

AB - Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

KW - Focal segmental glomerulosclerosis

KW - Immunosuppression

KW - Lipoid

KW - Nephrosis

KW - Nephrotic syndrome

KW - Transplantation

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U2 - 10.1007/s00467-018-3994-3

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