# THE ASSOCIATION OF BIOMARKERS OF ENDOTHELIAL FUNCTION WITH PROSPECTIVE CHANGES IN KIDNEY FUNCTION IN SICKLE CELL ANEMIA

> **NIH FDA R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $399,998

## Abstract

Sickle cell disease (SCD) is a severe monogenic disorder which affects approximately 80,000
patients in the US. It is characterized by a vasculopathy with involvement of multiple organs and
resulting in complications such as chronic kidney disease (CKD). Despite the high prevalence of CKD
in patients with SCD and its known association with increased mortality, the natural history of CKD in
this setting and the factors associated with changes in kidney function remain incompletely defined.
Furthermore, the available treatment options for albuminuria, an early manifestation of CKD, in
patients with SCD are limited. In fact, no controlled studies have confirmed the long-term efficacy of
angiotensin-converting enzyme (ACE) inhibitors, the current “standard of care.” There is increasing
evidence for a contribution of endothelial dysfunction to the pathophysiology of albuminuria in SCD.
The association of biomarkers of endothelial function with albuminuria provides opportunities, not only
to assess the effect of therapies which improve endothelial function, but also to evaluate the
predictive value of these biomarkers for a decline in kidney function.
Our overall hypothesis is that biomarkers of endothelial function will be predictive of patients with
sickle cell anemia at high risk for a decline in kidney function (decrease in estimated glomerular
filtration rate and increase in albuminuria). The analyses that we plan to perform would allow us to
identify those patients who are most likely to benefit from early treatment and will facilitate the
development of targeted therapies. In addition, this study will enable the development of a
biorepository of urine and plasma samples for future evaluation of the associations of changes in
metabolic profiles and other novel biomarkers with a decline in kidney function.
In this application, we will evaluate the rate of change of kidney function (eGFR and albuminuria) over
36 – 48 months; evaluate the cross-sectional association of biomarkers of endothelial function and
clinical characteristics with kidney function; and evaluate the cross-sectional association of urine and
plasma metabolomics profiles with kidney function. Finally, we will identify biomarkers of endothelial
function, metabolomic profiles and clinical characteristics for a worsening in kidney function and for a
rapid decline in kidney function, based on a decrease in eGFR of ≥ 2.5 mL/min per 1.73 m2 per year.
At the conclusion of our proposed work, we will have an improved understanding of the natural history
of CKD in sickle cell anemia. There are limited available therapies for the treatment of early CKD in
patients with SCD and there is a paucity of data on the long-term efficacy of available
pharmacotherapies. Identification of biomarkers for the progression of CKD will facilitate the
development of treatments which may be more effective than the current “standard of care.”

## Key facts

- **NIH application ID:** 10241267
- **Project number:** 5R01FD006030-06
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Kenneth I Ataga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $399,998
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241267

## Citation

> US National Institutes of Health, RePORTER application 10241267, THE ASSOCIATION OF BIOMARKERS OF ENDOTHELIAL FUNCTION WITH PROSPECTIVE CHANGES IN KIDNEY FUNCTION IN SICKLE CELL ANEMIA (5R01FD006030-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241267. Licensed CC0.

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