Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies

Approximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT₁R-Ab). While the role of AT₁R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT₁R-Ab.

We report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT₁R-Ab-mediated chronic ABMR. Because this antibody persisted during 4 years of hemodialysis, for the 2nd kidney transplantation (living-related transplantation from his mother), he underwent a desensitization regimen consisting of 15 plasmapheresis sessions, infusions of intravenous immunoglobulin G and thymoglobulin, as well as pharmacological blockade of the Angiotensin II (AT II) pathway by candesartan. This intense desensitization regimen transiently decreased elevated AT₁R-Ab titers, resulting in stable short-term kidney allograft function. The subsequent clinical course, however, was complicated by acute cellular rejection and chronic ABMR due to persistent AT₁R-Ab and de novo HLA-DSA, which shortened allograft survival to a period of only 4 years.

This case highlights the difficulty of persistently decreasing elevated AT₁R-Ab titers by a desensitization regimen for re-transplantation and the detrimental effect of the interplay between AT₁R-Ab and HLA-DSA on kidney transplant survival.