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Estimated glomerular filtration rate discordance and cardiopulmonary morbidity in sickle cell disease
Kabir Olaniran1, Alecia Nero1, Robert D Toto1,2
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Insights
Estimated glomerular filtration rate (eGFR) discordance is amplified in sickle cell disease (SCD), indicating higher cardiovascular risk. This eGFR discordance is linked to heart failure and pulmonary hypertension in SCD patients.
Area of Science:
- Nephrology
- Cardiology
- Hematology
Background:
- Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) is a known cardiovascular risk marker.
- The clinical significance of eGFR discordance in sickle cell disease (SCD) is not well understood.
Purpose of the Study:
- To evaluate the magnitude and clinical significance of eGFR discordance in adults with SCD compared to non-SCD controls.
- To assess the association between SCD and eGFR discordance, including high-risk discordance.
- To investigate the relationship between high-risk eGFR discordance and cardiopulmonary conditions within the SCD cohort.
Main Methods:
- Cross-sectional study of 1,099 Black adults (223 with SCD, 876 controls).
- eGFR discordance defined as the percentage difference between cystatin C- and creatinine eGFR.
- Propensity score overlap weighting used to balance covariates between SCD and control groups.
- Assessed association of SCD with continuous and high-risk eGFR discordance (cystatin C eGFR ≥30% lower than creatinine eGFR).
Main Results:
- SCD was significantly associated with more negative eGFR discordance (median difference -14.20%) and increased odds of high-risk discordance (aOR 1.88) compared to controls.
- Within the SCD cohort, high-risk discordance independently predicted prevalent heart failure (aOR 4.65) and pulmonary hypertension (aOR 2.70).
- Heart failure was the strongest predictor of more negative discordance; higher hemoglobin was linked to less negative discordance, suggesting hemolysis as a mechanism.
- eGFR discordance patterns differed between SCD and controls, particularly in advanced renal impairment.
Conclusions:
- eGFR discordance is disproportionately amplified in individuals with SCD.
- This amplified eGFR discordance may serve as a non-invasive biomarker for non-atherosclerotic cardiopulmonary risk in SCD.
- Further prospective studies are warranted to evaluate eGFR discordance in SCD management.
Abstract:
Discordance between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFR) is a recognized cardiovascular risk marker, but its magnitude and clinical significance in sickle cell disease (SCD) remain unknown. We conducted a cross-sectional study of 1099 Black adults (223 with SCD and 876 without SCD) to evaluate eGFR discordance, defined as the percentage difference between cystatin C and creatinine eGFR. Using propensity score overlap weighting to balance covariates, we assessed the association of SCD with continuous discordance and high-risk discordance (cystatin C eGFR ≥30% lower than creatinine eGFR). After overlap weighting, SCD was associated with a profoundly more negative eGFR discordance (adjusted median difference, -14.20%; 95% confidence interval [CI], -19.30 to -9.09) and increased odds of high-risk discordance (adjusted odds ratio [aOR], 1.88; 95% CI, 1.12-3.16) compared with controls. Within the SCD cohort, high-risk discordance was independently associated with prevalent heart failure (aOR, 4.65; 95% CI, 1.91-11.30) and pulmonary hypertension (aOR, 2.70; 95% CI, 1.19-6.17). In multivariable models, heart failure was the dominant independent correlate of more negative discordance, whereas higher hemoglobin was associated with less negative discordance, suggesting a hemolysis-driven mechanism. In trend analyses, eGFR discordance became progressively more negative with declining creatinine eGFR, then appeared to reverse at advanced renal impairment, a pattern absent in non-SCD controls. These findings show that eGFR discordance is disproportionately amplified in SCD and support the evaluation of eGFR discordance as a noninvasive biomarker of nonatherosclerotic cardiopulmonary risk in prospective SCD studies.
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