(LB02-23-25) Greater Changes in eGFR Associated With Higher Urine Albumin-to-Creatinine Ratio Among People With Sickle Cell Disease in Brazil

Objectives: Among children born with sickle cell disease (SCD), improved prevention strategies to reduce severe kidney failure risk across the lifespan remain elusive. Our objectives were to: 1) compare abnormal estimated glomerular filtration rate (eGFR) and albuminuria across age groups; and 2) evaluate influences of hemoglobin (Hb) and eGFR changes (Δ%) on urine albumin-to-creatinine ratio (UACR) among people with SCD.

Methods: In Recipient Epidemiology and Donor Evaluation Study, Brazil (REDS-III and -IV-P), a prospective cohort (2013-2024), people with SCD were enrolled in 2 phases. In this study, we evaluated 2 timepoints/participant, which we refer to as baseline and follow-up visits; Δ% was defined as the difference between timepoints. We categorized Δ% in quintiles (Q3 as reference); the lowest quintile (Q1) reflected the greatest decreases and highest quintile (Q5) reflected the greatest increases. eGFR was calculated with the CKD-EPI Creatinine Equation (2021); hyperfiltration was defined as high eGFR (men ≥140, women ≥130 mL/min/1.73m²). We evaluated associations in multivariable linear regressions with follow-up outcomes.

Results: Among cohort members, 1,266 participants (baseline median age 14 years [IQR 8, 23]) had complete data for this analysis. 71.0% had HbSS, 22.4%% had HbSC. Mean Δ% Hb was 3.4% (SD 15.9), ranging from -16.4% (Q1) to 25.8% (Q5) across quintiles. Mean Δ% eGFR was 2.5% (SD 18.3), and stratified by quintiles, ranged from -18.0% (Q1) to 27.2% (Q5). At follow-up, 10.3% of younger children ( < 10 years), 24.5% of older children (10-17 years), and 45.6% of adults had elevated UACR (≥30 mg/g; p< 0.01). Adjusted mean eGFR did not differ across quintiles of Δ% Hb (p _trend 0.06). Δ% Hb quintiles were associated with UACR (p _trend 0.04), accounting for covariates. Mean UACR was higher among people with greater increases (Q5: β 119.04 [SE 42.45]) and decreases (Q2: β 105.82 [SE 42.18]; Q1: β 117.82 [SE 42.56]) of Δ% eGFR (p _trend 0.02), adjusting for baseline Hb and covariates.

Conclusions: Our findings underscore the need for earlier albuminuria screening, determining long-term implications of reduced hyperfiltration in children, and confirmation of Δ% eGFR-UACR associations, accounting for contemporary SCD treatments.

Funding Sources: NIH (NHLBI), German Federal Ministry of Education and Research