Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

Abstract

Incompatible living donor kidney transplant recipients (ILDKTr) have pre‐existing donor‐specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25‐center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.031.682.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.452.093.02; PFNC = 1.672.403.46; PCC = 1.482.243.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.341.621.95) than CLDKT (aHR = 1.962.292.67) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Comparison of kidney transplant outcomes in HLA compatible and incompatible transplantation: A national cohort study

“…Transplant function at 1 and 3 years and graft survival were inferior following HLAi transplantation compared to HLAc transplantation and were negatively associated with prior AMR. Similar results of increased graft loss and mortality following incompatible transplantation, especially in the context of acute rejection, were suggested in a large multicenter trial by Motter et al in 2021 27 . Despite this, 3‐year graft survival in our cohort was good (87%), despite a higher risk of AMR following HLAi transplantation.…”

HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

“…A stepwise approach is commonly used to desensitize including, (i) either high-dose intravenous immunoglobulin (IVIG) or low dose IVIG in association with plasmapheresis to remove antibodies and, (ii) anti-CD20 targeting agent, such as rituximab, to prevent rebound antibodies development by B cell depletion (23)(24)(25)(26)(27). Regarding the kidney transplantation field, despite the desensitizing effect, the subsequent transplantation is associated with higher rate of rejection and higher rate of hospital readmission after transplantation (28)(29)(30). However, long term outcomes for patient and graft survival have been reported to be similar to that of non-sensitized patients (31).…”

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series

“…In the same cohort, Motter et al. ( 17 ) did show more acute rejection in Luminex-only DSA+ recipients as compared to DSA- controls, but this had less impact on DCGS in comparison to acute rejection in HLA compatible transplantations. Of note is that in these studies all DSA+ recipients underwent desensitization.…”