Dataset Information

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

ABSTRACT: The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.

SUBMITTER: Kamburova EG

PROVIDER: S-EPMC6899679 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Antibodies against ARHGDIB are associated with long-term kidney graft loss.

Kamburova Elena G EG Gruijters Maartje L ML Kardol-Hoefnagel Tineke T Wisse Bram W BW Joosten Irma I Allebes Wil A WA van der Meer Arnold A Hilbrands Luuk B LB Baas Marije C MC Spierings Eric E Hack Cornelis E CE van Reekum Franka E FE van Zuilen Arjan D AD Verhaar Marianne C MC Bots Michiel L ML Drop Adriaan C A D ACAD Plaisier Loes L Melchers Rowena C A RCA Seelen Marc A J MAJ Sanders Jan Stephan JS Hepkema Bouke G BG Lambeck Annechien J A AJA Bungener Laura B LB Roozendaal Caroline C Tilanus Marcel G J MGJ Voorter Christina E CE Wieten Lotte L van Duijnhoven Elly M EM Gelens Mariëlle A C J MACJ Christiaans Maarten H L MHL van Ittersum Frans J FJ Nurmohamed Shaikh A SA Lardy Neubury M NM Swelsen Wendy W van der Pant Karlijn A M I KAMI van der Weerd Neelke C NC Ten Berge Ineke J M IJM Hoitsma Andries A van der Boog Paul J M PJM de Fijter Johan W JW Betjes Michiel G H MGH Heidt Sebastiaan S Roelen Dave L DL Claas Frans H FH Bemelman Frederike J FJ Otten Henny G HG

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20190703 12

The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplante ...[more]

PMID: 31194283

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Project description:Rationale & objectiveSepsis-associated acute kidney injury often leads to acute kidney disease (AKD), predisposing patients to long-term complications such as chronic kidney disease (CKD), kidney failure with replacement therapy (KFRT), or mortality. Risk stratification of patients with AKD represents an opportunity to assist with prognostication of long-term kidney complications.Study designSingle-center retrospective cohort.Setting & participants6,290 critically ill patients admitted to the intensive care unit with severe sepsis or septic shock. Patients were separated into cohorts based on incident acute kidney injury or not, and survivors identified who were alive and free of KFRT up to 90 days.PredictorsAKD stage (0A, 0C, or ≥1) using the last serum creatinine concentration available by discharge or up to 90 days postdischarge.OutcomeTime to development of incident CKD, progression of CKD, KFRT, or death.Analytical approachMultivariable Cox proportional hazards models.ResultsPatients surviving kidney injury associated with sepsis often fail to return to baseline kidney function by discharge: 577/1,231 (46.9%) with stage 0C or 1 or greater AKD. AKD stage was significantly associated with the composite primary outcome. Stages 0C AKD and 1 or greater AKD were significantly and progressively associated with the primary outcome when compared with stage 0A AKD (adjusted HR [aHR], 1.74; 95% CI, 1.32-2.29, and aHR, 3.25; 95% CI, 2.52-4.20, respectively). Additionally, stage 1 or greater AKD conferred higher risk above stage 0C AKD (aHR, 1.87; 95% CI, 1.44-2.43). CKD incidence or progression and KFRT, more so than mortality, occurred with greater frequency in higher stages of AKD.LimitationsRetrospective design, single center, exclusion of patients with KFRT within 90 days of discharge, potential ascertainment bias, and inability to subclassify above AKD stage 1.ConclusionsRisk stratification using recommended AKD stages at hospital discharge or shortly thereafter associates with the development of long-term kidney outcomes following sepsis-associated acute kidney injury.

Dataset Information

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

Publications

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

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