# Biomolecular Markers for Safe Minimization of Immunosuppression

> **NIH NIH R37** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $374,941

## Abstract

We seek additional funds for research responsive to the SARS-CoV-2/COVID-19 outbreak that is in scope of
our ongoing grant R37AI051652 “Biomolecular Markers for Safe Minimization of Immuno-suppression.” From
March 13, 2020 to April 20, 2020, we hospitalized 39 kidney allograft recipients positive for SARS-CoV-2 and
with Covid-19 symptoms. Among these patients, 20 (51%) developed acute kidney injury (AKI). Importantly, graft
dysfunction due to AKI recovered in 9 patients only and did not recover in 11 patients as of May 15, 2020. None
underwent a diagnostic allograft biopsy because of biopsy-associated complications such as bleeding are
potentially much more serious in this cohort and also to limit potential exposure of healthcare workers to SARS-
CoV-2 during the invasive biopsy procedure. In the absence of a diagnostic biopsy, none received anti-rejection
therapy. Whether the graft dysfunction was reversible or nonreversible could not be predicted at the time of graft
dysfunction diagnosis. The dynamics of anti-allograft response from the reductions in their immunosuppressive
therapy could not be captured with the available clinical analytes. To address these existing challenges, we
propose the following: Specific Aim 1. To perform RNA sequencing of urinary cells and investigate
whether the urinary cell transcriptome, ascertained at the time of graft dysfunction, is prognostic of
allograft dysfunction. Urine will be collected at the time of graft dysfunction diagnosis and RNA isolated from
urinary cells. RNA from 30 patients with reversible graft dysfunction; RNA from 30 patients with nonreversible
graft dysfunction; and RNA from 30 patients with no graft dysfunction during the 3 months since Covid-19
diagnosis will be RNA sequenced and bioinformatics performed. The goal is to determine whether the urinary
cell transcriptome profile, ascertained at the time of graft dysfunction, is prognostic of graft dysfunction and
distinguishes those with reversible graft dysfunction from those with nonreversible graft dysfunction. Specific
Aim 2. To measure urinary cell 3-gene signature score in sequential urine samples from Covid-19 kidney
allograft recipients. Urine will be collected at baseline and sequentially every two weeks for 3 months since
Covid-19 diagnosis. We will retrieve 210 sequential samples from 30 Covid-19 kidney allograft recipients
(Baseline and 6 sequential samples from each patient) who developed reversible graft dysfunction; 210
sequential samples from 30 Covid-19 kidney allograft recipients who developed nonreversible graft dysfunction;
and 30 Covid-19 kidney allograft recipients who did not develop graft dysfunction during the 3-months since
Covid-19 diagnosis. RNA isolated from urinary cells will be reverse transcribed to cDNA and absolute copy
numbers of CD3E mRNA, CXCL10 mRNA and 18S rRNA will be measured using customized PCR assays and
urinary cell 3-gene signature score will be computed using a validated regression equation. The...

## Key facts

- **NIH application ID:** 10209348
- **Project number:** 3R37AI051652-15S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** MANIKKAM SUTHANTHIRAN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $374,941
- **Award type:** 3
- **Project period:** 2021-01-28 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209348

## Citation

> US National Institutes of Health, RePORTER application 10209348, Biomolecular Markers for Safe Minimization of Immunosuppression (3R37AI051652-15S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10209348. Licensed CC0.

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