Aims: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus.
Methods: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model.
Results: During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07-1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10-<30 mg/gCr) UACR.
Conclusions: Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation.
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Development of sandwich enzyme-linked immunosorbent assays quantifying mouse urinary megalin, a novel proximal tubular biomarker.
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Department of Applied Molecular Medicine, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan. Electronic address:
Article Synopsis
- Megalin is a multi-ligand endocytic receptor found in the apical membrane of proximal tubules and is noted for its presence in human urine in both ectodomain and full-length forms, with ectodomain being more prevalent.
- The study developed and validated two types of sandwich ELISAs—A-megalin and C-megalin—to specifically measure the ectodomain and full-length forms of megalin, respectively, in mouse urine.
- Findings indicated that A-megalin and C-megalin were detectable in normal mouse urine, but significantly reduced in mice with a megalin-knockout, highlighting the predominance of ectodomain forms in urine.
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Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Fukushima, Japan.
Aims: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes.
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The endocytosis receptor megalin: From bench to bedside.
Int J Biochem Cell Biol
April 2023
Departments of Applied Molecular Medicine, Japan. Electronic address:
The large (∼600 kDa) endocytosis receptor megalin/low-density lipoprotein receptor-related protein 2 is highly expressed at the apical membrane of proximal tubular epithelial cells (PTECs). Megalin plays an important role in the endocytosis of various ligands via interactions with intracellular adaptor proteins, which mediate the trafficking of megalin in PTECs. Megalin mediates the retrieval of essential substances, including carrier-bound vitamins and elements, and impairment of the endocytic process may result in the loss of those substances.
View Article and Find Full Text PDFUrinary A- and C-megalin predict progression of diabetic kidney disease: an exploratory retrospective cohort study.
J Diabetes Complications
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Department of Applied Molecular Medicine, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan. Electronic address:
Aims: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD).
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Urinary C-megalin as a novel biomarker of progression to microalbuminuria: A cohort study based on the diabetes Distress and Care Registry at Tenri (DDCRT 22).
Diabetes Res Clin Pract
April 2022
Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan; Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Fukushima 960-1295, Japan; Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima 960-1295, Japan; Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto 604-8006, Japan.
Aims: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus.
Methods: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr).
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