420.4 De Novo Complement-Activating Donor Specific Antibodies in Pediatric Renal Transplant Recipients are Highly Responsive to Therapy
Tuesday May 07, 2019 from 13:45 to 15:00
Bayshore D/E/F
Award Winner
Vaka K Sigurjonsdottir, United States has been granted the IPTA Scientific Award
Presenter

Vaka K Sigurjonsdottir, United States

Pediatric Nephrology Fellow

Pediatric Nephrology, Lucile Packard Children's Hospital at Stanford

Stanford

Abstract

De Novo Complement-Activating Donor Specific Antibodies in Pediatric Renal Transplant Recipients are Highly Responsive to Therapy

Vaka Sigurjonsdottir1, Bing M. Zhang2, Marcelo Fernandez Vina2, Abanti Chaudhuri1, Waldo Concepcion1,3, Amy Gallo1,3, Paul Grimm1.

1Department of Pediatric Nephrology, Stanford University, Palo Alto, CA, United States; 2Histocompatibility, Immunogenetics and Disease Profiling Laboratory, Stanford University, Palo Alto, CA, United States; 3Surgery - Multi-Organ Transplantation, Stanford University, Palo Alto, CA, United States

Introduction: Antibody mediated rejection remains a common cause for pediatric renal allograft loss. After recognizing that graft failure was more common in our pediatric renal transplant recipients with positive de Novo DSAs (dnDSAs) by C1q we started using the C1q assay as a guide to therapy. The aim of this study was to 1. Investigate evolution and response of C1q biomarker to treatment 2. Investigate allograft function and clinical characteristics of cohort.

Methods: This was a retrospective study. Pediatric renal transplant recipients transplanted 1/1/2010-1/1/2018 were considered for inclusion. dnDSAs were identified by routine screening from 2010 or at investigation of allograft dysfunction. Patients with least 6-month follow-up were included. dnDSAs were identified by single-antigen flow bead assay. Outcomes: - Evolution of C1q dnDSAs - Renal survival, defined as >50% decline of eGFR or progression to ESRD according to DSA status. - GFR was estimated using Schwartz method.

Results: A total of 262 patients were considered for inclusion, 220 met inclusion criteria. Age of patients was 12 years (11 mo21 y), (median, range), 47 % were female and 26% got a living donor transplant. Follow up was 34 months (6-88), (median, range). Figure 1

shows renal survival in the cohort according to DSA status after transplant, 45% (102) formed no DSA, 18 %(35) IgG only and 37%(83) C1q. Figure 2

shows the evolution of dnDSA by C1q over time after first detection in the post-transplant period. We compared renal survival in patients with eliminated C1q with therapy to those with persistent C1q.

Rejection therapy was per institution standard of care. However, treatment was intensified if DSAs by C1q was not eliminated. C1q was eliminated in 78% of patients (n=66.).

Conclusion: Persistent C1q positive DSA in spite of therapy is a strong predictor of poor graft outcome, Patients with a persistently positive C1q DSA should be considered for more aggressive therapy and participation in clinical trials.

Tashia and John Morgridge Endowed Postdoctoral Fellow.


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