Predictors of graft failure after first detection of de novo donor-specific HLA antibodies in kidney transplant recipients

Author:

López del Moral Covadonga12ORCID,Wu Kaiyin3,Naik Marcel1ORCID,Osmanodja Bilgin1,Akifova Aylin1,Lachmann Nils4,Stauch Diana4,Hergovits Sabine4,Choi Mira1,Bachmann Friederike1,Halleck Fabian1,Schrezenmeier Eva15,Schmidt Danilo1,Budde Klemens1ORCID

Affiliation:

1. Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Berlin , Germany

2. Department of Nephrology, Marqués de Valdecilla University Hospital-IDIVAL , Santander , Spain

3. Department of Pathology, Charité – Universitätsmedizin Berlin , Berlin , Germany

4. Institute for Transfusion Medicine, HLA-Laboratory, Charité – Universitätsmedizin Berlin , Berlin , Germany

5. Berlin Institute of Health Charité – Universitätsmedizin Berlin, BIH Academy , Berlin , Germany

Abstract

ABSTRACT Background De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection of dnDSAs during screening in asymptomatic patients. We aimed to assess the value of estimated glomerular filtration rate (eGFR) and proteinuria to predict graft failure in patients with dnDSAs and their potential utility as surrogate endpoints. Methods All 400 kidney transplant recipients with dnDSAs at our centre (1 March 2000–31 May 2021) were included in this retrospective study. The dates of graft loss, rejection, doubling of creatinine, ≥30% eGFR decline, proteinuria ≥500 mg/g and ≥1000 mg/g were registered from the first dnDSA appearance. Results During 8.3 years of follow-up, graft failure occurred in 33.3% of patients. Baseline eGFR and proteinuria correlated with 5-year graft loss (area under the receiver operating characteristics curve 0.75 and 0.80, P < .001). Creatinine doubled after a median of 2.8 years [interquartile range (IQR) 1.5–5.0] from dnDSA and the time from doubling creatinine to graft failure was 1.0 year (IQR 0.4–2.9). Analysing eGFR reduction ≥30% as a surrogate endpoint (148/400), the time from dnDSA to this event was 2.0 years (IQR 0.6–4.2), with a positive predictive value (PPV) of 45.9% to predict graft loss, which occurred after 2.0 years (IQR 0.8–3.2). The median time from proteinuria ≥500 mg/g and ≥1000 mg/g to graft failure was identical, 1.8 years, with a PPV of 43.8% and 49.0%, respectively. Composite endpoints did not improve PPV. Multivariable analysis showed that rejection was the most important independent risk factor for all renal endpoints and graft loss. Conclusions Renal function, proteinuria and rejection are strongly associated with graft failure in patients with dnDSA and may serve as surrogate endpoints.

Funder

Valdecilla Biomedical Research Institute

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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