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

Abstract

Background 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. Methods 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. Results Median follow‐up time was 8.6 years. 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). Conclusions 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.

Association of HLA B‐ and T‐cell molecular mismatches with HLA antibodies, rejection, and graft survival in pediatric kidney transplantation

“…In studies of molecular mismatches, dnDSA is commonly the primary end-point, and the number of molecular mismatches is associated with dnDSA in many pediatric studies. 9,36,38,39,41,42 In pediatric transplantation, the association between dnDSA and rejection/graft failure is not as strong as in adults, and while most studies show some association with reduced graft survival and rejection, 39,[43][44][45][46][47] the evidence is limited due to smaller sample sizes and fewer studies. Interestingly, our results did indicate a harmful effect of dnDSA on kidney function with a lower eGFR in recipients with dnDSA than in recipients without.…”

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice

“…[29,131] This indicates there is not enough evidence to state that DSA HLA-class significantly attenuates the risk of a rejection diagnosis or the graft prognosis and therefore should not influence the decision to omit a biopsy in patients with subclinical dnDSA. Multiple studies have associated other DSA characteristics with worse outcomes, such as MFI level (sum of all DSA MFI or highest individual MFI) [22,88,[132][133][134][135][136], certain IgG subclasses [55,137,138], or complement binding ability (C1q, C4d, C3d) [54]. However, most studies do not provide information on the negative predictive value of these characteristics, which would be the parameter of interest in deciding on whether to omit a biopsy.…”