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Transplantation. 2019 Jul 23. doi: 10.1097/TP.0000000000002889. [Epub ahead of print]

HLA class II antibodies at the time of kidney transplantation and cardiovascular outcome: a retrospective cohort study.

Author information

1
Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
2
HILA, Red Cross-Flanders, Mechelen, Belgium.

Abstract

BACKGROUND:

The negative role of HLA class II DSA on graft outcome is well-recognized. However, the potentially negative cardiovascular effects of preformed HLA class II antibodies and donor HLA in kidney transplant recipients (KTR) remain unestablished.

METHODS:

We conducted a single-centre, retrospective cohort study including 1115 KTR (2003-2016) with up to 4449 person-years of follow-up after transplantation and a median follow-up time of 5.1 years (IQR: 2.7-7.6). We evaluated the unadjusted and multivariable-adjusted association between pretransplant HLA class I and II antibodies, as well as HLA-DR1 donor/recipient genotype and the primary (MACCE or all-cause mortality) and secondary (MACCE or cardiovascular mortality) outcome.

RESULTS:

In a multivariate Cox proportional hazard model, HLA class II antibodies prior to transplantation were associated with increased adjusted hazard ratio (aHR) for MACCE or all-cause mortality (aHR 1.71 [1.13-2.60]; p=0.012) even after adjustment for time-varying covariates graft loss (aHR 1.68 [1.08-2.62]; p=0.022) and biopsy-proven acute rejection (aHR 1.71 [1.13-2.60]; p=0.012). HLA class II antibodies were also associated with increased aHR for the secondary outcome, MACCE or cardiovascular mortality (aHR 1.92 [1.12-3.30]; p=0.018). We investigated the effect of donor and recipient HLA-DR1 on these outcome parameters and demonstrated that KTR with HLA-DR1 positive donors had an increased aHR for MACCE with all-cause (aHR1.45 [1.09-1.94], p=0.012) and cardiovascular mortality (aHR1.49 [1.00-2.22], p=0.05).

CONCLUSIONS:

Prior sensitization against HLA class II antigens is associated with unfavourable long-term cardiovascular outcome in KTR independent of graft loss or rejection. Recipients of a HLA-DR1 donor also have an impaired cardiovascular outcome.

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