Estimated Glomerular Filtration Rate Discordance and Cardiopulmonary Morbidity in Sickle Cell Disease.

Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) is a recognized cardiovascular risk marker, yet its magnitude and clinical significance in sickle cell disease (SCD) remain unknown. We conducted a cross-sectional study of 1,099 Black adults (223 with SCD and 876 non-SCD controls) to evaluate eGFR discordance, defined as the percentage difference between cystatin C- and creatinine eGFR. Utilizing propensity score overlap weighting to balance covariates, we assessed the association of SCD with continuous discordance and high-risk discordance (cystatin C eGFR ³30% lower than creatinine eGFR). Following 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 to 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 to 11.30) and pulmonary hypertension (aOR, 2.70; 95% CI, 1.19 to 6.17). In multivariable models, heart failure was the dominant independent associate of more negative discordance, while higher hemoglobin was associated with less negative discordance, suggesting a hemolysis-driven mechanism. On trend analyses, eGFR discordance became progressively more negative with declining creatinine eGFR, appearing to reverse at advanced renal impairment, a pattern absent in non-SCD controls. These findings demonstrate that eGFR discordance is disproportionately amplified in SCD and support the evaluation of eGFR discordance as a non-invasive biomarker of non-atherosclerotic cardiopulmonary risk in prospective SCD studies.