Urinary Proteomic Signatures in Sickle Cell Disease: Search for Biomarkers Associated With Underlying Molecular...

Identifying urinary biomarkers of sickle cell disease (SCD) may provide insights into disease mechanisms and support improved disease monitoring. In this pilot study, we analyzed the urinary proteome of 32 SCD patients (children and adults, steady state, and various genotypes) and 19 healthy controls using mass spectrometry-based proteomics. A total of 2263 proteins were detected, of which 978 were consistently quantified across groups. Ninety proteins showed differential abundance between SCD patients and controls, with 26 upregulated and 64 downregulated in SCD. Upregulated proteins included those associated with cellular stress response (e.g., DNA damage-inducible 1 homolog 2) and immune activation, whereas proteins involved in hemoglobin clearance and mitochondrial metabolism were downregulated, consistent with hemolysis and mitochondrial dysfunction. These findings suggest that urinary proteomics can capture systemic processes relevant to SCD pathophysiology. Despite the small and heterogeneous cohort, this study highlights candidate urinary biomarkers and molecular pathways that warrant validation in larger, stratified cohorts to assess their potential for disease monitoring.