Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation

Vikas R. Dharnidharka; Rebecca R. Scobell; Mahmoud Kallash; Amy J.Goodwin Davies; Nicole Marchesani; Mitchell G. Maltenfort; Leslie Walther; Megan Kelton; Margret Bock; Eliza Blanchette; Hillarey K. Stone; Caroline Gluck; Frank Hullekes; Leonardo V. Riella; William E. Smoyer; Mark Mitsnefes; Bradley P. Dixon; Joseph T. Flynn; Michael J.G. Somers; Christopher B. Forrest; Susan Furth; Michelle R. Denburg

doi:10.1007/s00467-024-06452-z

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation

Vikas R. Dharnidharka
, Rebecca R. Scobell
, Mahmoud Kallash
, Amy J.Goodwin Davies
, Nicole Marchesani
, Mitchell G. Maltenfort
, Leslie Walther
, Megan Kelton
, Margret Bock
, Eliza Blanchette
, Hillarey K. Stone
, Caroline Gluck
, Frank Hullekes
, Leonardo V. Riella
, William E. Smoyer
, Mark Mitsnefes
, Bradley P. Dixon
, Joseph T. Flynn
, Michael J.G. Somers
, Christopher B. Forrest

Susan Furth, Michelle R. Denburg

Washington University St. Louis
The Children's Hospital of Philadelphia
Ohio State University
University of Washington
University of Colorado School of Medicine
Cincinnati Children's Hospital Medical Center
Massachusetts General Hospital
Boston Children's Hospital
University of Pennsylvania

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.

METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.

RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.

CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Original language	English
Pages (from-to)	3317-3331
Number of pages	15
Journal	Pediatric Nephrology
Volume	39
Issue number	11
DOIs	https://doi.org/10.1007/s00467-024-06452-z
State	Published - Nov 2024

Keywords

Adolescent
Child
Female
Glomerulosclerosis, Focal Segmental/diagnosis
Graft Survival/drug effects
Humans
Immunosuppressive Agents/therapeutic use
Kidney Transplantation/adverse effects
Male
Nephrotic Syndrome/diagnosis
Recurrence
Remission Induction
Retrospective Studies
Risk Factors
Treatment Outcome
United States/epidemiology

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10.1007/s00467-024-06452-z

Cite this

Dharnidharka, V. R., Scobell, R. R., Kallash, M., Davies, A. J. G., Marchesani, N., Maltenfort, M. G., Walther, L., Kelton, M., Bock, M., Blanchette, E., Stone, H. K., Gluck, C., Hullekes, F., Riella, L. V., Smoyer, W. E., Mitsnefes, M., Dixon, B. P., Flynn, J. T., Somers, M. J. G., ... Denburg, M. R. (2024). Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation. Pediatric Nephrology, 39(11), 3317-3331. https://doi.org/10.1007/s00467-024-06452-z

@article{ec254e546d8f434fb527c9e15b87622e,

title = "Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation",

abstract = "BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6\%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2\% and partial remission in 17.9\%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.",

keywords = "Adolescent, Child, Female, Glomerulosclerosis, Focal Segmental/diagnosis, Graft Survival/drug effects, Humans, Immunosuppressive Agents/therapeutic use, Kidney Transplantation/adverse effects, Male, Nephrotic Syndrome/diagnosis, Recurrence, Remission Induction, Retrospective Studies, Risk Factors, Treatment Outcome, United States/epidemiology",

author = "Dharnidharka, \{Vikas R.\} and Scobell, \{Rebecca R.\} and Mahmoud Kallash and Davies, \{Amy J.Goodwin\} and Nicole Marchesani and Maltenfort, \{Mitchell G.\} and Leslie Walther and Megan Kelton and Margret Bock and Eliza Blanchette and Stone, \{Hillarey K.\} and Caroline Gluck and Frank Hullekes and Riella, \{Leonardo V.\} and Smoyer, \{William E.\} and Mark Mitsnefes and Dixon, \{Bradley P.\} and Flynn, \{Joseph T.\} and Somers, \{Michael J.G.\} and Forrest, \{Christopher B.\} and Susan Furth and Denburg, \{Michelle R.\}",

note = "{\textcopyright} 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.",

year = "2024",

month = nov,

doi = "10.1007/s00467-024-06452-z",

language = "English",

volume = "39",

pages = "3317--3331",

journal = "Pediatric Nephrology",

issn = "0931-041X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "11",

}

Dharnidharka, VR, Scobell, RR, Kallash, M, Davies, AJG, Marchesani, N, Maltenfort, MG, Walther, L, Kelton, M, Bock, M, Blanchette, E, Stone, HK, Gluck, C, Hullekes, F, Riella, LV, Smoyer, WE, Mitsnefes, M, Dixon, BP, Flynn, JT, Somers, MJG, Forrest, CB, Furth, S & Denburg, MR 2024, 'Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation', Pediatric Nephrology, vol. 39, no. 11, pp. 3317-3331. https://doi.org/10.1007/s00467-024-06452-z

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation. / Dharnidharka, Vikas R.; Scobell, Rebecca R.; Kallash, Mahmoud et al.
In: Pediatric Nephrology, Vol. 39, No. 11, 11.2024, p. 3317-3331.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation

AU - Dharnidharka, Vikas R.

AU - Scobell, Rebecca R.

AU - Kallash, Mahmoud

AU - Davies, Amy J.Goodwin

AU - Marchesani, Nicole

AU - Maltenfort, Mitchell G.

AU - Walther, Leslie

AU - Kelton, Megan

AU - Bock, Margret

AU - Blanchette, Eliza

AU - Stone, Hillarey K.

AU - Gluck, Caroline

AU - Hullekes, Frank

AU - Riella, Leonardo V.

AU - Smoyer, William E.

AU - Mitsnefes, Mark

AU - Dixon, Bradley P.

AU - Flynn, Joseph T.

AU - Somers, Michael J.G.

AU - Forrest, Christopher B.

AU - Furth, Susan

AU - Denburg, Michelle R.

PY - 2024/11

Y1 - 2024/11

N2 - BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

AB - BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

KW - Adolescent

KW - Child

KW - Female

KW - Glomerulosclerosis, Focal Segmental/diagnosis

KW - Graft Survival/drug effects

KW - Humans

KW - Immunosuppressive Agents/therapeutic use

KW - Kidney Transplantation/adverse effects

KW - Male

KW - Nephrotic Syndrome/diagnosis

KW - Recurrence

KW - Remission Induction

KW - Retrospective Studies

KW - Risk Factors

KW - Treatment Outcome

KW - United States/epidemiology

UR - https://www.scopus.com/pages/publications/85198428497

U2 - 10.1007/s00467-024-06452-z

DO - 10.1007/s00467-024-06452-z

M3 - Article

C2 - 39001911

AN - SCOPUS:85198428497

SN - 0931-041X

VL - 39

SP - 3317

EP - 3331

JO - Pediatric Nephrology

JF - Pediatric Nephrology

IS - 11

ER -

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation

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