# Pretransplant comprehensive scores to predict long term graft outcomes

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $232,512

## Abstract

Despite the improved short-term outcomes in kidney transplantation (KT), comparable progress in long-term
allograft survival has not been achieved. Chronic allograft dysfunction (CAD) characterized by interstitial fibrosis
and tubular atrophy (IFTA), accounts for one quarter of transplant kidneys lost within 5 years. Preventing kidney
graft dysfunction and loss is a critical unmet need in transplantation. From reported evidence, posttransplant
graft survival is determined by the complex interplay of donor factors, acute peri-transplantation injury, and
kidney transplant recipient factors. We recently reported that the transcriptome of deceased donor kidneys
encompasses a gene signature at the time of KT that predicts long-term graft function. These signatures shed
light on the inherent donor mechanisms responsible for triggering and likely sustaining posttransplant injury.
Furthermore, although a recipient peripheral blood transcriptional signature was recently reported as a predictor
of early acute rejection, the effect of pretransplant KT recipient peripheral blood transcriptional profiles on long-
term outcomes has not been previously tested. Moreover, there are no comprehensive biological markers
from donors and recipients that can be used pretransplant to predict graft outcomes. Given the multifactorial
nature of CAD, our preliminary data, and the gaps in our knowledge, we have the unique ability to fill these unmet
needs by studying the early stressors that lead to kidney graft fibrosis deploying an unbiased comprehensive
approach. Towards this goal, we have already established a cohort with prospective sequential sampling of
kidney allografts. In our studies, donor kidneys were evaluated at pre-implantation and recipient pretransplant
peripheral blood mononuclear cells (PBMCs) were collected. The recipient cohort also includes longitudinal
PBMCs, protocol biopsies, and detailed clinical metadata, allowing for the correlation of gene expression profiles
with histological features and clinical parameters. In this exploratory proposal, we hypothesize that early cellular
and molecular events in the donor kidney trigger local inflammatory responses that, when combined with
recipient immune state, propagate and sustain posttransplant kidney injury leading to graft loss. Specific aims
(SA) include: SA1 (1) Identify kidney transplant recipient preimplantation peripheral blood molecular profiles that
associate with immune activation vs quiescence and determine posttransplant graft function. (2) Discern
longitudinal posttransplant molecular variations in patient's PBMCs that associate with long-term graft function.
SA2 Integrate kidney donor and recipient peripheral blood gene expression profiles in association with
donor/recipient clinical characteristics for constructing a composite score to predict long-term outcomes.
IMPACT: Results of these studies will provide a unique understanding of the early molecular triggers that
determine graft outcomes...

## Key facts

- **NIH application ID:** 10810725
- **Project number:** 5R21AI172077-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Kellie J. Archer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,512
- **Award type:** 5
- **Project period:** 2023-03-16 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810725

## Citation

> US National Institutes of Health, RePORTER application 10810725, Pretransplant comprehensive scores to predict long term graft outcomes (5R21AI172077-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10810725. Licensed CC0.

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