TY - JOUR
T1 - Factors at de novo donor-specific antibody initial detection associated with allograft loss
T2 - a multicenter study
AU - Schinstock, Carrie A.
AU - Dadhania, Darshana M.
AU - Everly, Matthew J.
AU - Smith, Byron
AU - Gandhi, Manish
AU - Farkash, Evan
AU - Sharma, Vijay K.
AU - Samaniego-Picota, Milagros
AU - Stegall, Mark D.
N1 - Funding Information:
Carrie Schinstock received support from CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Evan
Funding Information:
The authors have declared no funding. Carrie Schinstock received support from CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Evan Farkash received support from NIAID 1K23AI108951. We acknowledge the work of Jennifer Mawby for her work as a research coordinator.
Publisher Copyright:
© 2019 Steunstichting ESOT
PY - 2019/5
Y1 - 2019/5
N2 - We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.
AB - We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.
KW - HLA-antibody post-transplantation
KW - histocompatibility and immunogenetics
KW - infection
KW - kidney clinical
KW - other
KW - rejection
UR - http://www.scopus.com/inward/record.url?scp=85061291304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061291304&partnerID=8YFLogxK
U2 - 10.1111/tri.13395
DO - 10.1111/tri.13395
M3 - Article
C2 - 30597643
AN - SCOPUS:85061291304
SN - 0934-0874
VL - 32
SP - 502
EP - 515
JO - Transplant International
JF - Transplant International
IS - 5
ER -