Tubular Cell Dropout in Preimplantation Deceased Donor Biopsies as a Predictor of Delayed Graft Function.

Abstract

Delayed graft function (DGF) affects over 25% of deceased donor kidney transplants (DDKTs) and is associated with increased cost, worsened graft outcomes, and mortality. While approaches to preventing DGF have focused on minimizing cold ischemia, donor factors such as acute tubular injury can influence risk. There are currently no pharmacologic therapies to modify DGF risk or promote repair, in part due to our incomplete understanding of the biology of preimplantation tubular injury. We collected intraoperative, preimplantation kidney biopsies from 11 high-risk deceased donors and 10 living donors and followed transplant recipients for graft function. We performed quantitative high-dimensional histopathologic analysis using imaging mass cytometry to determine the cellular signatures that distinguished deceased and living donor biopsies as well as deceased donor biopsies which either did or did not progress to DGF. We noted decreased tubular cells (P < 0.0001) and increased macrophage infiltration (P = 0.0037) in high-risk DDKT compared with living donor biopsies. For those high-risk DDKTs that developed postimplant DGF (n = 6), quantitative imaging mass cytometry analysis showed a trend toward reduced tubular cells (P = 0.02) and increased stromal cells (P = 0.04) versus those that did not (n = 5). Notably, these differences were not identified by conventional histopathologic evaluation. The current study identifies donor tubular cell loss as a precursor of DGF pathogenesis and highlights an area for further investigation and potential therapeutic intervention.