# Improving Scientific Rigor of Renal Clinical Endpoints for Sickle Cell Anemia

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $942,101

## Abstract

Project Summary
Patients living with sickle cell anemia (SCA) are at high risk for morbidity and mortality associated with renal
disease. To improve the clinical outcomes for SCA patients, we must ensure a scientifically rigorous approach
to monitoring disease progression. In pediatric SCA, an elevated glomerular filtration rate (hyperfiltration)
precedes the development of chronic kidney disease (CKD). Up to 70% of SCA adults will develop CKD and
among patients that progress to end-stage renal disease (ESRD) and require dialysis, one quarter of patients
die within the first year of starting dialysis. The evidence is clear that we must accurately identify SCA patients
at risk for ESRD and early death so that clinicians can intervene prior to the development of ESRD.
The gold standard method for monitoring SCA kidney disease progression, measured glomerular filtration rate
(mGFR) is too time consuming for annual clinical care monitoring as it requires injection of a filtration marker
(iohexol) and measuring blood clearance of this marker over at least six hours. Our research team validated a
novel, time-efficient mGFR approach in non-SCA patients by injecting visible fluorescent imaging (VFI) and
measuring blood clearance over three hours. Estimated glomerular filtration rate (eGFR) equations provide an
alternative approach to monitoring a patient's kidney function using a single blood sample measurement (cystatin
and/or creatinine). eGFR has been validated in non-SCA patients with high accuracy and precision. However,
our preliminary data and work of others clearly demonstrate that the eGFR equations are not valid in SCA. The
difference between eGFR and mGFR is seven times higher and the standard deviation is three times higher in
SCA studies as compared to the non-SCA validation studies. By including SCA-relevant variables (hemoglobin
and reticulocyte count) to the standard GFR variables, the preliminary data shows an improvement in the
precision of novel SCA-specific eGFR equations by 25%.
This proposal addresses the critical barriers for future SCA research due to the systematic bias in monitoring
renal disease progression in SCA patients. Using the gold standard iohexol mGFR, this proposal will use
biologically plausible SCA-relevant variables to develop novel SCA-specific eGFR equations in children and
adults and compare the precision and accuracy of these equations against standard eGFR equations (aim 1).
To validate these equations for use in annual clinical monitoring and design of future clinical trials, we will
measure the concordance (one year) between the novel and standard eGFR equations to mGFR (aim 2). Finally,
as mGFR (iohexol) is not time-efficient for monitoring SCA patients in clinic, we will test the correlation of VFI
mGFR performed over 3 hours to iohexol mGFR performed over 6 hours (aim 3). If successful, our work will
improve the systematic bias of clinical research using GFR endpoints in SCA. This will improve our clinica...

## Key facts

- **NIH application ID:** 10636876
- **Project number:** 5R01HL153386-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jeffrey D Lebensburger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $942,101
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10636876

## Citation

> US National Institutes of Health, RePORTER application 10636876, Improving Scientific Rigor of Renal Clinical Endpoints for Sickle Cell Anemia (5R01HL153386-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10636876. Licensed CC0.

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