ArticlePediatric nephrology (Berlin, Germany)2026
Urinary megalin expression in children with sickle cell nephropathy.
Article in Pediatric nephrology (Berlin, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSickle cell nephropathy (SCN) is a common and under-recognized complication of sickle cell disease (SCD) in children. While albuminuria is widely used as an early marker of renal disease in SCD, emerging evidence suggests that tubular dysfunction may play a critical role in SCN pathogenesis. Megalin -a renal tubular receptor- is essential for albumin reabsorption and may serve as a biomarker of tubular injury. There is a paucity of human studies assessing the relationship between megalin and albuminuria. This study aimed to evaluate the association between urinary level of megalin and spot urine albumin-creatinine ratio (UACR) in children with sickle cell anemia (SCA) compared with those of age- and sex-matched hemoglobin A (HbAA) controls.
methodsThis hospital-based comparative cross-sectional study included 120 steady-state SCA children and 120 HbAA controls. Early morning urine was assayed for megalin and albumin, using enzyme-linked immunosorbent assay (ELISA) and UACR respectively.
resultsChildren with SCA had higher UACR and greater prevalence of SCN (UACR ≥ 3 mg/mmol) than healthy controls (3.6 ± 2.8 vs. 2.0 ± 1.7 mg/mmol, p = 0.001, and 30.8% vs. 14.2%, p = 0.003, respectively). Urinary megalin levels were similar in SCA (1459.3 ± 483.1 ng/L) and controls (1552.3 ± 662.4 ng/L), p = 0.215. However, urine megalin was significantly lower in children with SCN (1063.3 ± 388.4 ng/L) compared to children with SCA without nephropathy (1635.8 ± 683.6 ng/L, p = 0.002) and compared to albuminuric controls (1592.4 ± 530.8 ng/L, p = 0.001). There was a significant negative correlation between urinary megalin and UACR in SCA subjects (r = -0.4, p = 0.001) as well as in the SCN subgroup (r = -0.5, p = 0.000). No such correlation was found in controls.
conclusionIn children with SCN, urine megalin concentration, reflecting renal tubule megalin expression, is decreased in comparison to children with SCA without nephropathy and inversely associated with UACR. Further experimental and clinical studies are needed to understand megalin regulation in SCN and whether downregulation is protective or not for tubular damage.
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