# Mechanisms of venous thrombosis and renal dysfunction in sickle trait

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $720,846

## Abstract

Worldwide, there are an estimated 300 million individuals who are carriers of the sickle cell β-globin gene (a
condition known as ‘sickle cell trait’ (SCT)). While generally regarded as a benign condition, SCT has been
shown to be associated with venous thrombosis and chronic kidney disease. We propose that harsh biophysical
conditions within venous thrombi or in the inner renal medulla induce sickling of SCT red blood cells (RBCs) that
promotes activation of coagulation and reduced RBC deformability while increasing RBC adhesiveness. To test
this hypothesis, we will use both human SCT blood samples as well as heterozygous (AS) Townes sickle cell
mice to study the RBC-dependent mechanisms that lead to venous thrombosis and chronic kidney disease. We
have established that AS mice develop larger experimental venous thrombi than control animals. Additionally,
like their human counterparts, AS mice manifest early onset glomerular hyperfiltration and albuminuria with age-
dependent reduction in glomerular filtration rate. Sub-contracts with the University of Alabama at Birmingham
and Johns Hopkins University will augment the recruitment of human subjects with SCT at UNC Chapel Hill.
Blood from all subjects will be analyzed in the UNC Blood Research Center using a panel of laboratory assays
that mimic the biophysical environments encountered by RBCs in the kidney or within newly formed blood clots.
The mouse model studies will be used to test the ability of anti-sickling, anti-thrombotic and anti-adhesive
therapies to prevent/reduce enhanced venous thrombosis and renal dysfunction observed in the AS mice.

## Key facts

- **NIH application ID:** 10778484
- **Project number:** 1R01HL171501-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nigel S. Key
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $720,846
- **Award type:** 1
- **Project period:** 2024-02-15 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778484

## Citation

> US National Institutes of Health, RePORTER application 10778484, Mechanisms of venous thrombosis and renal dysfunction in sickle trait (1R01HL171501-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10778484. Licensed CC0.

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