ESPN 50th Annual Meeting

ESPN 2017


 
Clinical Risk Stratification of Paediatric Renal Transplant Recipients Using C1q and C3d Fixing of de novo Donor Specific Antibodies
JON JIN KIM 1 OLIVIA SHAW 4 CHLOE MARTIN 4 GEORGE MICHAELIDES 5 NEIL SEBIRE 2 NIZAM MAMODE 3 ANTHONY DORLING 3 ROBERT VAUGHAN 4 STEPHEN MARKS 2

1- NOTTINGHAM UNIVERSITY HOSPITAL
2- GREAT ORMOND STRET HOSPITAL FOR CHILDREN
3- MRC CENTRE FOR TRANSPLANTATION, GUYS HOSPITAL, LONDON
4- VIAPATH CLINICAL TRANSPLANTATION LABORATORY, GUYS HOSPITAL, LONDON
5- BIRKBECK, UNIVERSITY OF LONDON
 
Introduction:

We previously showed that children who developed de novo donor specific HLA antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement activating DSA would have poorer renal allograft outcomes. 

Material and methods:

75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. Primary event was defined as 50% reduction from baseline estimated glomerular filtration rate (eGFR) and was analysed using Kaplan-Meier estimator. Serial DSA positive samples were subsequently tested for C3d fixing and MFI results were correlated with eGFR using multi-level models.

Results:

Of 65 patients tested, 32 (49%) and 23 (35%) were positive for C1q and C3d fixing respectively. 13/32 (41%) C1q positive patients did not show concomitant C3d fixing. MFI values of original IgG DSA correlated poorly with complement fixing positivity [C1q: adjusted R2=0.072; C3d: adjusted R2=0.11, p<0.05]. C1q+ antibodies were associated with acute tubulitis [C1q+ 0.75(± 0.18) v C1q- 0.25(± 0.08) episodes per patient, p<0.05] but not worse long-term renal allograft dysfunction [median time to primary event C1q+ 5.9 v C1q- 6.4 years, p=0.58]. C3d+ antibodies were associated with positive C4d histological staining [C3d+ 47% v C3d- 20%, p=0.04] and significantly worse long-term allograft dysfunction [median time to primary event C3d+ 5.6 v C3d- 6.5 years, p = 0.04]. Changes in C3d MFI did not correlate with eGFR over time. 

 

Conclusions:

 Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at highest risk of long-term renal allograft dysfunction.