ESPN 54th Annual Meeting

ESPN 2022


 
Landscape of subclinical rejection in a large international cohort of pediatric kidney transplant (kTx) recipients
JULIEN HOGAN 11 ROUBA GARRO 2 GILLIAN DIVARD 1 OLIVIA BOYER 3 JODI SMITH 4 KATHERINE TWOMBLEY 5 BRAD WARADY 6 PATRICIA WENG 7 RIMA ZAHR 8 RACHEL PATZER 9 ALEXANDRE LOUPY 1 ALTON BRAD FARRIS 10

1- PARIS TRANSPLANT GROUP, UNIVERSITY OF PARIS, PARCC, INSERM, FRANCE
2- PEDIATRIC NEPHROLOGY, CHILDREN HEALTHCARE OF ATLANTA, EMORY UNIVERSITY, ATLANTA, GA, USA
3- PEDIATRIC NEPHROLOGY, NECKER HOSPITAL, APHP, PARIS, FRANCE
4- PEDIATRIC NEPHROLOGY, SEATTLE CHILDREN, SEATTLE, NY, USA
5- PEDIATRIC NEPHROLOGY, MEDICAL UNIVERSITY OF SOUTH CAROLINA, CHARLESTON, SC, USA
6- PEDIATRIC NEPHROLOGY, CHILDREN’S MERCY, KANSAS CITY, MI, USA
7- PEDIATRIC NEPHROLOGY, DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA, LOS ANGELES, CA, USA
8- PEDIATRIC NEPHROLOGY, LE BONHEUR CHILDRENS HOSPITAL, MEMPHIS, TN, USA
9- EMORY TRANSPLANT CENTER, DEPARTMENT OF SURGERY, EMORY UNIVERSITY, ATLANTA, GA, USA
10- DEPARTMENT OF PATHOLOGY, EMORY UNIVERSITY SCHOOL OF MEDICINE, ATLANTA, GA, USA
11- PEDIATRIC NEPHROLOGY, ROBERT DEBRE HOSPITAL, APHP, PARIS, FRANCE
 
Introduction:

Kidney allograft rejection can occur in clinically stable patients, but long-term significance in pediatric kTx recipients is unknown. Previous single-center studies demonstrated that subclinical borderline (SC-Borderline) or T-cell mediated rejection (SC-TCMR) are associated with an increased risk of acute rejection. However, the prevalence and significance of subclinical antibody-mediated rejection (SC-AMR) and the impact of subclinical rejection phenotypes on graft survival remained to be assessed.

Material and methods:

We used data from pediatric (<21) patients transplanted between 2005 and 2017 from 8 institutions in France and the United States performing surveillance biopsies. Biopsies were identified as surveillance if they were recorded as such in the medical record with no significant increase in serum creatinine or proteinuria. Biopsies were graded according to the Banff 2019 criteria. DSA screening was performed according to each center protocol. Kaplan Meier method and log-rank test were used to compare the risk of acute rejection, transplant glomerulopathy and graft loss stratified on the surveillance biopsies’ findings.

Results:

1390 surveillance biopsies were performed in 763 kTx recipients including 135 (9,7%) SC-borderline, 46 (3,3%) SC-TCMR, 54 (3,9%) SC-ABMR, 8 (0,6%) subclinical mixte rejections. Subclinical rejection was associated with acute rejection with 5-year rejection-free survival of 88%, 78%, 68% and 63% in the no rejection, SC-borderline, SC-TCMR and SC-AMR groups, respectively (p<0,0001). SC-TCMR and SC-AMR were associated with the development of transplant glomerulopathy, p<0,0001. Subclinical AMR only was associated with a lower 5-year graft survival (79% vs. 93% (SC-TCMR), 95% (SC-Borderline), 94% (no rejection)), p=0,002.

Conclusions:

Subclinical rejection is prevalent in pediatric kidney recipients without clinical dysfunction and is associated with acute rejection. Subclinical AMR is associated with the development of transplant glomerulopathy and with an increased risk of allograft failure.