Estimated glomerular filtration rate discordance and cardiopulmonary morbidity in sickle cell disease.

abstractDiscordance 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.