Potential hyperacute renal rejection due to non-hla antibody in a pediatric patient

Abstract

Non-HLA antigen targets have been associated with hyperacute, acute, and chronic kidney allograft rejection. Although there is controversy regarding the predictive role of non-HLA antibodies (Abs) in transplant (Txp) outcome - there are cases that indicate causality between the presence of such Abs and graft loss. A 17 month old boy with end-stage kidney disease, secondary to kidney dysplasia, received a living donor Txp from his uncle in April 2014. The presence of HLA abs was tested in 5 sera samples prior to Txp with a PRA of 7% and 0% for class I and II respectively (flow PRA). Single antigen testing confirmed the absence of donor specific HLA Abs (DSA). Initial and final flow cross matches were negative, as expected. During the Txp surgery, it was noted that the kidney became firm, urine output was below expectation and the child became increasingly pressor-dependent. Subsequently, the patient had an episode of ventricular tachycardia and an exploratory laparotomy demonstrated that the Txp kidney became tense and enlarged, with thrombosis of the renal vein. The kidney was nephrectomized within 48 hours and the patient’s status improved significantly. To investigate a potential role for HLA DSA, we tested a 2 days post-Txp serum sample, confirming the absence of HLA-DSA. We also repeated Abs testing on the pre-Txp serum sample ruling out HLA-DSA as the cause of rejection. To assess potential causes for this apparently hyperacute Ab mediated rejection, pre-Txp (pre-14 days) and post-Txp (post-24 days) samples were sent out for AT1R Abs screening and donor specific endothelial cell crossmatch (XM-One). Retrospective testing of a pre- and post-Txp sera for AT1R antibody was out of range for pre-Txp sample and the post-Txp sample was positive ( > 30 Units/ml). The XM-One assay using endothelial precursors isolated from the donor as targets was strongly positive using a pre-Txp serum but negative using post-Txp serum. Approximately two month’s post-Txp, the patient developed HLA Abs, on top of the AT1R antibodies. In conclusion, this patient still requires a kidney Txp and the question is how to proceed – shall we consider only obtaining an organ from a living donor? This would allow for the necessary time to run XM-One and potentially inhibit AT1R pathway with an AT 1 receptor antagonist. What to do if no living donor becomes available?