# Assessment of Donor Quality for Improving Kidney Transplant Outcomes

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $672,483

## Abstract

Kidney transplant (KT) short-term outcomes have steadily improved over the last several decades, however,
similar progress in long-term allograft survival has not yet been reached largely due to chronic allograft injury
(CAI). In our previous funding cycle, we identified a gene expression signature in deceased donor kidney biopsies
at pre-KT that was predictive of graft function, measured by eGFR, at 24-months post-KT. Further, our single-
cell/nucleus transcriptome profiles yielded several important findings including that KT recipients with acute
kidney injury have increased fibroblasts and macrophages (both donor- and recipient-origin) with a macrophage
subset characterized by fibroblast-like markers; donor-derived macrophages were present in functioning kidney
grafts with interstitial fibrosis and tubular atrophy (IFTA) more than 24-mo post-KT; and paired single-cell
peripheral blood mononuclear cells (PBMCs) showed immune cell type specific profiles reflecting graft injury.
Thus, our results revealed the unappreciated role of donor kidney cells (immune and non-immune) on tissue
repair and local immunomodulation, which plays a critical role in response to injury and determines graft function.
Moreover, post-KT graft survival is determined by a complex interplay between donor and recipient factors. Thus,
our findings guided the establishment of our new hypothesis that early measurable donor and donor-recipient
cellular interactions and molecular profiles are strong indicators of chronic inflammatory responses and
maladaptive repair circuits, shaping long-term graft outcomes. Therefore, in this funding cycle, we will
elucidate the effects of donor cell type-specific drivers of injury that exacerbate the initial donor/recipient immune-
and non-immune cell interactions in response to injury and determine how these events are reflected in the
peripheral samples, allowing non-invasive graft monitoring by using cell type-specific markers of injury. This will
be accomplished by leveraging our large unique available resource that includes donor biopsies (pre-KT) with
paired longitudinal recipient biopsies and PBMCs (post-KT) along with KT recipient clinical outcomes to pursue
the following specific aims: Aim 1. Assess donor and recipient cells' origin, function, and interactions that play a
role in graft injury. Aim 2. Uncover cell type-specific molecular signatures from peripheral immune cells derived
from KT recipients at pre-implantation and longitudinally post-KT, reflecting immune risk status and kidney graft
function. Aim 3. Establish a novel statistical method for developing a composite score using high-dimensional
donor/recipient molecular and clinical/demographic variables to predict graft function. This study will provide (i)
cell type-specific gene signatures and regulatory regions that control the transition between healthy and diseased
kidney graft states, eventually guiding efforts to reprogram cells to promote repair after injury, (ii) ...

## Key facts

- **NIH application ID:** 10901576
- **Project number:** 2R01DK109581-06A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Kellie J. Archer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $672,483
- **Award type:** 2
- **Project period:** 2017-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901576

## Citation

> US National Institutes of Health, RePORTER application 10901576, Assessment of Donor Quality for Improving Kidney Transplant Outcomes (2R01DK109581-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10901576. Licensed CC0.

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