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.
N1 - © 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.
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 -