Incidence, risk factors, management strategies, and outcomes of antibody-mediated rejection in pediatric kidney transplant recipients-a multicenter analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)

Abstract

Background: This study by the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) was designed to determine the incidence, risk factors, current management strategies, and outcomes of antibody-mediated rejection (ABMR) in pediatric kidney transplant recipients (pKTR).

Methods: We performed an international, multicenter, longitudinal cohort study of data reported to the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. Three hundred thirty-seven pKTR from 21 European centers were analyzed. Clinical outcomes, including kidney dysfunction, rejection, HLA donor-specific antibodies, BK polyomavirus-associated (BKPyV) nephropathy, and allograft loss, were assessed through 5 years post-transplant.

Results: The cumulative incidence of de novo donor-specific class I HLA antibodies (HLA-DSA) post-transplant was 4.5% in year 1, 8.3% in year 3, and 13% in year 5; the corresponding data for de novo class II HLA-DSA were 10%, 22.5%, and 30.6%, respectively. For 5 years post-transplant, the cumulative incidence of acute ABMR was 10% and that of chronic active ABMR was 5.9%. HLA-DR mismatch and de novo HLA-DSA, especially double positivity for class I and class II HLA-DSA, were significant risk factors for ABMR, whereas cytomegalovirus (CMV) IgG negative recipient and CMV IgG negative donor were associated with a lower risk. BKPyV nephropathy was associated with the highest risk of graft dysfunction, followed by ABMR, T-cell mediated rejection, and older donor age.

Conclusions: This study provides an estimate of the incidence of de novo HLA-DSA and ABMR in pKTR and highlights the importance of BKPyV nephropathy as a strong risk factor for allograft dysfunction.

Keywords: DnDSA development; Antibody-mediated rejection; BKPyV nephropathy; Graft outcome; Pediatric kidney transplantation; Risk factors.

A higher resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

Cumulative incidence of de novo HLA-DSA during the first 5 years post-transplant. The red line indicates class I HLA-DSA, the blue line indicates class II HLA-DSA, and the shaded areas indicate the respective 95% confidence intervals. A Data reported by the respective transplant centers according to the center-specific cut-off for HLA-DSA positivity. B Data calculated using a uniform MFI cut-off value of 1400

Fig. 2

Cumulative incidence of acute antibody-mediated rejection (ABMR) and chronic active ABMR during the first 5 years post-transplant. The red line indicates acute ABMR; the blue line indicates chronic active ABMR; shaded areas indicate 95% confidence interval

Fig. 3

Allograft survival probability of acute ABMR (n = 30, red line) and chronic active ABMR (n = 16, blue line). Patients with mixed ABMR and TCMR (n = 13) were assigned to the ABMR category determined by the histologic lesions, in this analysis always the acute ABMR category. Analysis was performed using a semi-Markov multi-state model. Follow-up time is taken from the time of the event (clock reset model). The grey line indicates patients without ABMR