Proximal tubulopathy in adult sickle cell disease: association of alpha-1 microglobulin

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BACKGROUND: Sickle cell nephropathy remains a major contributor to morbidity in adults with Sickle Cell Disease (SCD), yet proximal tubular injury remains insufficiently characterized, particularly in African settings. Alpha-1 Microglobulin (A1M), a low-molecular-weight protein, may serve as a sensitive biomarker of proximal tubular dysfunction. METHODS: The authors conducted a multicentre observational cross-sectional study among 246 adults with stable SCD in Kinshasa, Democratic Republic of the Congo. Proximal tubulopathy was defined as A1M/Cr ≥ 20 mg/g. Measured Glomerular Filtration Rate (mGFR) was assessed by plasma iohexol clearance. Associations were evaluated using a pre-specified multivariable logistic regression model with multiple imputation for missing data. RESULTS: Proximal tubulopathy was present in 48% of participants. After adjustment, vaso-occlusive crises during the previous trimester (aOR = 1.96, 95% CI 1.14-3.35), leg ulcers (aOR = 2.11, 95% CI 1.16-3.82), and albuminuria (log-transformed UACR; aOR = 1.53, 95% CI 1.24-1.88) were independently associated with elevated A1M/Cr. Hydroxyurea use was associated with lower odds of proximal tubulopathy (aOR = 0.54, 95% CI 0.31-0.95). In a model adjusted for albuminuria, no independent associations were observed for markers of hemolysis or measured GFR, suggesting that the effects of these factors on tubular injury may be mediated through glomerular injury or are closely intertwined with it. Sensitivity analyses excluding albuminuria from the model (Tables S2-S5) did show associations with leg ulcer, recent VOC, and systolic blood pressure. CONCLUSIONS: Proximal tubular dysfunction is frequent among adults with SCD in this high-burden African setting and was independently associated with markers of disease severity and renal involvement.

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