# Clinical and Molecular Biomarkers of Endpoints in Pediatric Renal Transplantation

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $297,000

## Abstract

Abstract
Nearly all pediatric and young adult (PYA) kidney transplants fail within 10-15 years, significantly reducing life
expectancy for young people with end-stage renal disease (ESRD). Pediatric kidney transplant recipients face
distinct barriers to allograft survival, including diagnostic and prognostic tools that are inadequate and not tailored
for children. Consequently, kidney transplant injury regularly escapes detection until substantial damage has
occurred that hastens allograft failure. Surveillance biopsies allow for earlier detection of subclinical injury prior
to transplant dysfunction, but we have shown that the presence of subclinical phenotypes are still predictive of
transplant failure. Improved methods of detecting clinical and subclinical kidney transplant endpoints are needed
to increase longevity of youth with ESRD. Recent studies have validated patterns of gene expression (e.g.,
molecular biomarkers) in adult kidney transplant biopsies with greater diagnostic precision than conventional
histology. Similar advances with molecular biomarkers have not been translated to children. The objective of this
proposal is address this unmet clinical need by identifying and validating molecular biomarkers of key outcomes
in young kidney transplant recipients. We will integrate clinical features, traditional histology, and molecular
biomarkers to create powerful tools for precision diagnosis and prediction of long-term outcomes that are tailored
for PYA kidney transplants. Our central hypothesis is that distinctive gene expression patterns in kidney biopsies
will predict clinical and subclinical events in young transplant recipients and expand the capabilities of traditional
histology. The central hypothesis was formulated by our preliminary data in which we identified molecular
biomarkers of WNT pathway activation as novel predictors of kidney transplant injury and subsequent allograft
failure, even in individuals with reassuring clinical features and normal traditional histology. We will test the
central hypothesis by using the NanoString platform to interrogate archived PYA kidney transplant biopsies in
pursuit of three specific aims. In aim 1, we will identify molecular biomarkers of clinical endpoints in PYA kidney
transplantation. We expect that PYA-specific molecular biomarkers will: a) have excellent diagnostic
performance for clinical endpoints, b) help discriminate cases with diagnostic uncertainty by traditional histology,
and c) outperform conventional clinical features and histology for predicting long-term outcomes in youth. In aim
2, we will discern the role of subclinical molecular phenotypes in PYA kidney transplantation. We expect to find
unique molecular biomarkers of subclinical endpoints that will outperform conventional histology in predicting
future rejection episodes and allograft failure. In aim 3, we will validate clinical and molecular biomarkers as
predictors of kidney transplant outcomes in a prospective bio...

## Key facts

- **NIH application ID:** 10096754
- **Project number:** 1R01DK126807-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Michael Edward Seifert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $297,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096754

## Citation

> US National Institutes of Health, RePORTER application 10096754, Clinical and Molecular Biomarkers of Endpoints in Pediatric Renal Transplantation (1R01DK126807-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10096754. Licensed CC0.

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