Abstract Objective To evaluate biomarkers of glomerular, tubular, and endothelial function in patients with sickle cell disease (SCD), focusing on differences between hemolysis-dominant and vaso-occlusion–dominant subphenotypes. Methods This monocenter exploratory pilot study included 25 patients with SCD (21 HbSS, 4 HbSC) from the Radboud Iron Biobank. Primary analyses were restricted to 12 adults with HbSS, categorized into hemolysis‑dominant (HD, n = 8) and vaso‑occlusion–dominant (VOD, n = 4) subphenotypes. Serum and urine samples were collected during routine outpatient visits in clinically stable patients without any signs of sickle cell crises. Biomarkers reflecting glomerular function, tubular injury, and endothelial activation were quantified using nephelometry, ELISA, and routine clinical chemistry assays. Associations between biomarkers and clinical parameters were assessed using non‑parametric correlation analyses. Results Microalbuminuria was observed in five adults, mainly in the hemolysis-dominant (HD) subgroup (n = 4. No cases of macroalbuminuria were identified. Other urinary markers (NGAL, KIM-1) were within reference intervals and did not distinguish between clinical subphenotypes; urinary cystatin C was largely unquantifiable. Findings in children were comparable, with no evidence of albuminuria. Exploratory analyses suggested lower renal biomarker levels in hydroxyurea-treated patients. Correlation analyses revealed a hemolysis-associated cluster, with strong associations between sFLT-1 and LDH, bilirubin, and reticulocytes. Conclusion In this outpatient cohort, overt sickle cell nephropathy was not evident, and urinary biomarkers were largely within the reference intervals in a stable clinical situation without sickle cell crises. However, a hemolysis-associated endothelial signature was observed, involving sFLT-1. Larger longitudinal studies are needed to validate these preliminary findings before implementation in clinical practice.
Hoving et al. (Wed,) studied this question.