ArticleFrontiers in endocrinology2026
Differences in urinary biomarker profiles in patients with nephrotic-range proteinuria with and without hypoalbuminemia: a single-center cross-sectional study.
Article in Frontiers in endocrinology, 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
Background: Patients with chronic kidney disease (CKD) presenting as nephrotic-range proteinuria (NR, ≥3.5g/d) exhibit distinct clinical phenotypes with and without hypoalbuminemia. The underlying mechanisms need further investigation. Methods: This retrospective study included patients with CKD hospitalized over the past two years with baseline 24-hour urine total protein (24-hUTP) exceeding 3.5g. Based on whether their baseline serum albumin (ALB) levels were ≤30 g/L, patients were assigned to two groups: the nephrotic syndrome (NS) group and the isolated nephropathy-range proteinuria (isolated NR) group. Clinical indicators and urine tubular injury biomarkers were compared between the two groups. The Spearman correlation coefficient was used to analyze the association between clinical indicators and urinary biomarker profiles. Urinary biomarkers and the isolated NR phenotype were evaluated for their independent association using multivariate logistic regression analysis. Results: In all, 134 patients were divided into 83 isolated NR and 51 NS groups. Urinary transferrin (uTRF) and N-acetyl-β-D-glucosaminidase (uNAG) were higher in the NS group than in the isolated NR group. The isolated NR group, in contrast, had significant high level of urinary retinol-binding protein (uRBP). Additionally, the two groups' uRBP exhibited distinct correlation patterns with proteinuria. Multivariate logistic regression study demonstrated that uRBP and uTRF were independently linked to the phenotypes after controlling for relevant variables. Conclusions: Patients with NR with and without hypoalbuminemia exhibited distinct urinary biomarker profiles. Higher uRBP levels in patients without hypoalbuminemia may indicate differences in proximal tubular handling of low-molecular-weight proteins. In contrast, higher uTRF and uNAG levels in patients with hypoalbuminemia may reflect greater glomerular permeability abnormalities accompanied by tubular cellular injury. These findings are hypothesis-generating, and the potential involvement of megalin-mediated protein handling requires direct experimental and histopathological validation.
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