Megalin receptor shows promise as diabetic nephropathy biomarker
MedWire News: The endocytic receptor megalin may be a valuable biomarker of progression in diabetic nephrophathy, research shows.
Detection of certain parts of the megalin protein, which is expressed at the apical membrane of proximal tubule cells, in the urine appears to correlate with the severity of diabetic nephropathy in patients with Type 2 diabetes.
Akihiko Saito (Niigata University Graduate School of Medical and Dental Sciences, Japan) and co-workers measured urinary levels of megalin with monoclonal antibodies to the amino and carboxy termini of the protein - the A-megalin and C-megalin assays, respectively - in 68 patients with Type 2 diabetes.
They report in Diabetes Care that the A-megalin assay detected an ectodomain of megalin in the soluble fraction of urine, whereas the C-megalin assay detected a full-length form in both soluble and insoluble urinary fractions.
Indeed, they linked urinary C-megalin levels to the severity of diabetic nephropathy. Significantly higher levels were detected in patients with normoalbuminuria than in normal controls; increasing levels were seen with increasing albuminuria; and a closer association was detected between C-megalin and low estimated glomerular filtration rate (eGFR; <60mL/min/1.73m2) than urinary albumin.
By contrast, A-megalin showed potential as a biomarker for early stage diabetic nephropathy; urinary levels were high in patients with normo- and microalbuminuria, but not in patients with macroalbuminuria.
Saito and co-workers write: "Collectively, the urinary full-length form of megalin could be a novel biomarker associated with the severity of diabetic nephropathy and related disorders in patients with Type 2 diabetes."
They continue: "The urinary megalin ectodomain may be a distinctive regulated intramembrane proteolysis (RIP)-related biomarker that appears to be involved in the mechanisms of early [diabetic nephropathy]."
The clinical utility of the two urinary forms of megalin should be further investigated in prospective studies, the team concludes.
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By Cher Thornhill