# Utility of Biomarkers of Rejection and Kidney Injury in Tailoring Liver Transplant Immunosuppression

> **NIH NIH U01** · NORTHWESTERN UNIVERSITY · 2022 · $1,791,523

## Abstract

Project Summary/Abstract
The advent of molecular biomarkers holds great promise, both from a diagnostic perspective as well as the ability
to predict a disease state early enough to inform therapy and change clinical outcomes. In the last several years,
studies have suggested a role for biomarker profiling in the management of immunosuppression in liver
transplant recipients. From our CTOT-14 study data, we have developed key biomarkers that can detect early
signs of under- (rejection) and over- (chronic kidney disease) immunosuppression, particularly with use of
standard calcineurin-inhibitor therapy. But as the accuracy of molecular diagnostics improves, and as technology
platforms evolve, two important questions have surfaced regarding their value in the management of liver
transplant recipients. First, can biomarkers inform patient management and optimize the ability to personalize
immunosuppressive therapy? Second, can we characterize key pathways of immune activation and kidney injury
to further optimize the use of biomarkers and identify new therapeutic targets? We believe that these questions
comprise the next frontier in biomarker research, and we have therefore formulated this proposal to test a set of
hypotheses that relate directly to these questions. First, in a prospective multi-center clinical trial of liver
transplant recipients, we will challenge the `standard of care' and test the hypothesis that serial blood biomarker
profiling can identify patients at risk of kidney injury after liver transplantation and also guide the removal of
nephrotoxic calcineurin-inhibitor therapy safely without adversely increasing acute rejection. To achieve this
objective, we will leverage these immune and kidney biomarkers developed in our CTOT-14 validation study to
detect early signs of rejection and kidney injury to enhance proactive, safe withdrawal of calcineurin-inhibitors in
favor of non-nephrotoxic mTOR-inhibitors. This biomarker-guided interventional approach will be tested against
current standard management and also risk-stratify patients into those needing or not needing such
interventions. Second, we will leverage the clinical trial sample collections to gain deeper understanding of what
leads to rejection or alternatively what is protective of rejection. We will accomplish this by performing an
extensive battery of blood immune cell, antibody, genomic and proteomic profiling during the interventions to
best identify the pathways leading to our outcomes. In addition, we will simultaneously perform novel kidney
imaging biomarkers to ask what leads to kidney injury vs. protection in our unique cohorts. Together, the clinical
trial and accompanying mechanistic studies will allow us to cross the next frontier in biomarker research in
transplantation, namely the ability to use biomarkers to monitor the state of immune responsiveness and drug
toxicity to inform therapeutic decisions. Our clinical data and bio-banked samples will create a new ...

## Key facts

- **NIH application ID:** 10482420
- **Project number:** 5U01AI163081-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOSH LEVITSKY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,791,523
- **Award type:** 5
- **Project period:** 2021-09-06 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482420

## Citation

> US National Institutes of Health, RePORTER application 10482420, Utility of Biomarkers of Rejection and Kidney Injury in Tailoring Liver Transplant Immunosuppression (5U01AI163081-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10482420. Licensed CC0.

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