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Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Kim, JJ; Shaw, O; Martin, C; Michaelides, G; Balasubramaniam, R; Sebire, NJ; Mamode, N; ... Marks, SD; + view all (2017) Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies. Pediatric Nephrology 10.1007/s00467-017-3772-7. Green open access

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Abstract

INTRODUCTION: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. METHODS: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan-Meier estimator. RESULTS: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R (2) 0.072; C3d: adjusted R (2) 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q-) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q-) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30-1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d-); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d-) years; HR 0.38; 95% CI 0.15-0.97; p = 0.04]. CONCLUSION: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction.

Type: Article
Title: Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00467-017-3772-7
Publisher version: http://dx.doi.org/10.1007/s00467-017-3772-7
Language: English
Additional information: © The Author(s) 2017. This article is an open access publication
Keywords: Complement fixation, Donor-specific antibodies, HLA antibodies, Prognosis, Renal transplant
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1575824
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