Impact of de novo donor-specific HLA antibodies on pediatric kidney transplant prognosis in patients with acute declined or stable allograft function.

Abstract

This retrospective multicenter long-term cohort study investigates de novo donor-specific HLA antibodies (dnDSA) impact on allograft survival in pediatric kidney transplantation (KTx), depending on allograft function at dnDSA detection. Seventy patients with dnDSA screening in the context of acute allograft dysfunction (AAD) (>50% serum creatinine increase) or routine follow-up were included during a 20-year period. Number of dnDSA specificities and HLA total mean fluorescence intensity (MFI-sum) were collected. Median follow-up time was 8.6years. Among the 22 dnDSA+ patients, 8 patients presented AAD. Compared with dnDSA- patients, allograft survival was shorter only in dnDSA+/AAD+ patients, regardless of dnDSA detection during the 5-year post-transplant period (9 patients) or later (13 patients) (log rank p < .001 and p < .001, respectively). One dnDSA+/AAD-, 7 dnDSA+/AAD+, and 5 dnDSA- patients lost their allograft. Allograft survival was shorter in dnDSA+/AAD+ patients compared with the 16 dnDSA-/AAD+ patients (log rank p < .001) but did not differ between dnDSA+/AAD- and dnDSA-/AAD- patients (log rank p = .157). dnDSA+/AAD+ and dnDSA-/AAD+ patients presented higher risk of allograft failure compared with the other patient groups after adjustment for recipient age at KTx, donor type, and incidence of delayed graft function (HR 11.322, 95% CI 3.094-41.429, p < .001). Concurrent MFI-sum >10 000 and multiple dnDSA specificities were more significantly associated with AAD, compared with each factor separately (p < .001). In pediatric KTx, AAD shortens allograft survival in dnDSA+ patients, regardless of dnDSA time detection, and is commonly observed when high MFI-sum concurs with multiple dnDSA specificities. dnDSA without AAD incidence does not determinately affect allograft survival.