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

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A Correction to this article was published on 15 November 2018

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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.

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Change history

  • 15 November 2018

    The original version of this article unfortunately contained a mistake. The subtitle “A Midwest Pediatric Nephrology Consortium (MWPNC) study” was missing. The correct title including subtitle is given above.

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Funding

National Institute of Health (NIH) and National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) 5R01DK098135 and 5R01DK094987 to RG. RG and JDV are recipients of the Doris Duke Clinical Research Mentorship grant award. JHP, KK, and AB are supported by the Duke Pediatric Research Scholar (DPRS) program.

Author information

Author notes

  1. Jonathan H. Pelletier, Karan R. Kumar and Rachel Engen contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Divisions of Nephrology and Critical Care, Duke University Medical Center, Durham, NC, 27710, USA

    Jonathan H. Pelletier, Karan R. Kumar, Adam Bensimhon, Jennifer D. Varner, John W. Foreman, Delbert R. Wigfall, Annabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Shashi K. Nagaraj & Rasheed A. Gbadegesin

  2. Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois and Children’s Hospital Seattle, Washington, USA

    Rachel Engen

  3. University of Minnesota Masonic Children’s Hospitals, Minneapolis, MN, USA

    Michelle N. Rheault

  4. Children’s Mercy Hospital, Kansas City, MO, USA

    Tarak Srivastava

  5. Louisiana State University Children’s Hospital, New Orleans, Louisiana, USA

    Caroline Straatmann

  6. Connecticut Children’s Medical Center, Hartford, CT, USA

    Cynthia Silva

  7. St. Louis Children’s Hospital, St Louis, MO, USA

    T. Keefe Davis

  8. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Scott E. Wenderfer & Eileen D. Brewer

  9. North Carolina Children’s Hospital, Chapel Hill, NC, USA

    Keisha Gibson

  10. C.S. Mott Children’s Hospital, Ann Arbor, MI, USA

    David Selewski

  11. University of Virginia Children’s Hospital, Charlottesville, Virginia, USA

    John Barcia

  12. Mattel Children’s Hospital University of California, California, Los Angeles, USA

    Patricia Weng

  13. The Hospital for Sick Children, Toronto, ON, Canada

    Christoph Licht & Natasha Jawa

  14. Nationwide Children’s Hospital, Columbus, OH, USA

    Mahmoud Kallash

  15. Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Larry A. Greenbaum

Authors
  1. Jonathan H. Pelletier
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  2. Karan R. Kumar
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  5. Jennifer D. Varner
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  6. Michelle N. Rheault
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  8. Caroline Straatmann
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  9. Cynthia Silva
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  10. T. Keefe Davis
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  14. John Barcia
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  15. Patricia Weng
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  16. Christoph Licht
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  17. Natasha Jawa
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  18. Mahmoud Kallash
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  19. John W. Foreman
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  20. Delbert R. Wigfall
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  21. Annabelle N. Chua
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  22. Eileen Chambers
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  23. Christoph P. Hornik
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  24. Eileen D. Brewer
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  25. Shashi K. Nagaraj
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  26. Larry A. Greenbaum
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  27. Rasheed A. Gbadegesin
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Corresponding author

Correspondence to Rasheed A. Gbadegesin.

Ethics declarations

Each center completed a local institutional review board approval and data usage agreements with the coordinating center at Duke University. Individual centers independently performed chart review to identify eligible patients as determined by the inclusion and exclusion criteria.

Conflict of interest

The authors declare that they have no conflict of interest.

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Pelletier, J.H., Kumar, K.R., Engen, R. et al. Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings. Pediatr Nephrol 33, 1773–1780 (2018). https://doi.org/10.1007/s00467-018-3994-3

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  • DOI: https://doi.org/10.1007/s00467-018-3994-3

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