Impact of low‐level pretransplant donor‐specific antibodies on outcomes after kidney transplantation

Abstract

Background: The effect of low-level pretransplant donor-specific antibody (DSA) on kidney transplant outcomes is not well described. The goal of this study was to compare outcomes among patients of varying immunologic risk, based on the level of pretransplant DSA. Methods:We retrospectively reviewed all adult kidney transplant recipients who had undergone a transplant at our center between January 2013 and May 2017. Patients were grouped as negative DSA (mean fluorescence intensity, [MFI SUM < 100]), low-level DSA (MFI SUM 100-1000), and positive DSA (MFI SUM > 1000). Rejection, infection, graft, and patient survival were outcomes measured. Results: Of 952 patients, 82.1% had negative DSA, 10.7% had low-level DSA, and 7.1% had positive DSA. The positive DSA group had the highest rate of antibody-mediated rejection (10.3%), followed by low-level DSA (7.8%) and the negative DSA group (4.5%) (p = .034). The rate of BK viremia was highest in the positive DSA group (39.7%), followed by the low-level group (30.4%) and the negative DSA group (25.6%), (p = .025). None of the other outcomes, including graft or patient survival, were different between the groups. Conclusion: While low-level DSA should not prevent proceeding with kidney transplantation, it should not be ignored. Future studies are needed to investigate the long-term effects of varying levels of pre-transplant DSA on outcomes.

DSA in solid organ transplantation: is it a matter of specificity, amount, or functional characteristics?

“…The association of preformed HLA-DSAs with poor kidney allograft outcomes has been long established in the literature. Recent large and international cohort studies (with n = 3237–4724 patients) have confirmed and validated this well described association across multiple settings including deceased donor transplantation, analyses of recipient pairs receiving a kidney from the same donor and living donor transplantation [17 ▪ ,18,19]. In addition, other studies (with n = 174–924 patients) have confirmed that performed HLA-DSAs with MFI> 3000 were associated with decreased kidney allograft survival [20 ▪▪ ,21].…”

BSHI and BTS UK guideline on the detection of alloantibodies in solid organ (and islet) transplantation

“…Thammanichanond and colleagues (Thammanichanond et al, 2012) showed that recipients with a negative CDCXM but positive DSA detected by Luminex™ had a higher incidence of AMR but with no statistically significant impact on delayed graft function, patient survival or 1-and 5-year graft survival, when compared with DSA negative patients. Similarly, (Parajuli, Bath, et al, 2021) did not see any effect of DSA on graft or patient survival. In con- • Whether the donor is homozygous at a given loci (and MFI level of DSA doubled) • Presence of supertypic antibodies such as Bw4…”

Determination of the clinical relevance of donor epitope‐specific HLA‐antibodies in kidney transplantation

“…The MFI level does not sufficiently predict long‐term graft outcome due to well‐known limitations of the SAB assay (prozone effect, bead saturation, shared epitope phenomenon, etc.) 10,11 . In addition, it has been suggested that especially complement binding DSAs are pathogenic.…”

“…8,9 The MFI level does not sufficiently predict long-term graft outcome due to wellknown limitations of the SAB assay (prozone effect, bead saturation, shared epitope phenomenon, etc.). 10,11 In addition, it has been suggested that especially complement binding DSAs are pathogenic. Although biopsies of rejected grafts showed positive C4d deposition, [12][13][14] convincing evidence has emerged that antibody-mediated rejection could also occur in absence of positive C4d staining.…”