# Molecular and Cellular Analysis of Allograft Loss in Kidney Transplant Biopsies

> **NIH NIH R21** · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · 2022 · $247,531

## Abstract

African Americans (AAs) have higher risk for kidney allograft loss after kidney transplantation compared with
other races. Our Deterioration of Kidney Allograft Function Genomics study (DeKAF: U19 AI070119) showed a
significant disparity in allograft loss after the first biopsy for chronic allograft dysfunction (CGD) between AAs
and non-AAs. The DeKAF study enrolled nearly 3,000 transplant recipients, from 2005 to 2011, and conducted
genome wide association studies (GWAS). DeKAF participants are linked to the United States Renal Data
System (USRDS) for long-term clinical data. We defined AA by self-report and verified by GWAS principal
components. CGD was defined as >25% increase in creatinine relative to a 3-month baseline and is
associated with allograft loss. Although 91% of CGD biopsies have inflammation, not all progress to allograft
loss. The molecular and cellular differences between AA and non-AA CGD biopsies are unknown; biopsies
from the DeKAF cohort can be leveraged to determine these differences. To address kidney allograft loss
disparities after CGD, we aim to determine the molecular and cellular differences between AA and non-AA
CGD biopsies and associations with allograft loss. Due to established roles for macrophages and natural killer
(NK) cells in allograft rejection, the central hypothesis is that these cell types have higher abundance in AA
CGD biopsies and these cell types will be associated with increased risk for kidney allograft loss. We will
determine differences in Macrophage (Aim 1) and NK Cell (Aim 2) abundance in CGD kidney allograft biopsies
between AAs and on-AAs and association with allograft loss. We will use Digital Spatial Profiling (DSP) to
determine differences between AA and non-AA CGD biopsies. DSP combines fluorescent imaging of tissue
structures and whole transcriptome profiling. DSP is innovative because it differentiates RNA and protein
expression in separate tissue compartments such as tubules, interstitium or glomerulus. The reason for the
DSP approach: Histology showed more fibrosis in the interstitial areas of the kidney allografts and increased
tubular atrophy in AA CGD biopsies from DeKAF, but not what cell types are associated with kidney damage.
We will evaluate CGD biopsies in each of 4 groups: 1) AAs with allograft loss 2) AAs without allograft loss 3)
non-AAs with allograft loss and 4) non-AAs without allograft loss. We expect to find higher abundance of
macrophages and NK cells associated with AAs and allograft loss. This proposal will develop the innovative
DSP technology to assess CGD biopsies leading to a definition of the molecular, cellular and spatial
differences in AAs and non-AAs kidney allografts and study associations with allograft loss. This study will lead
to creation of a spatial atlas of various cell types and transcripts in AA and non-AA biopsies that associate with
allograft loss. This study should develop a wealth of data, as the foundation for a mechanistic and
intervention...

## Key facts

- **NIH application ID:** 10511352
- **Project number:** 1R21AI171826-01
- **Recipient organization:** HENNEPIN HEALTHCARE RESEARCH INSTITUTE
- **Principal Investigator:** Casey R Dorr
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,531
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511352

## Citation

> US National Institutes of Health, RePORTER application 10511352, Molecular and Cellular Analysis of Allograft Loss in Kidney Transplant Biopsies (1R21AI171826-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10511352. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*