Nephronectin expression in glomeruli of renal biopsy specimens from various kidney diseases: nephronectin is expressed in the mesangial matrix expansion of diabetic nephropathy.

In a previous proteomic study, we detected increased expression of nephronectin in the glomeruli from patients with diabetic nephropathy (DN). The aim of the present study was to clarify the usefulness of determining glomerular expression of nephronectin in kidney disease. We performed immunohistochemical staining for nephronectin in renal biopsy specimens from patients with a variety of kidney diseases (n = 190). The percentage of nephronectin-positive areas in the glomeruli was analyzed using an image analyzer. Nephronectin immunoreactivity was clearly, strongly positive in the mesangial expansion and nodular lesions of DN (n = 18), whereas nephronectin immunoreactivity was negative in IgA glomerulonephritis, membranoproliferative glomerulonephritis, lupus nephritis, membranous glomerulonephritis, minor glomerular abnormalities, crescentic glomerulonephritis, and other kidney diseases, such as amyloidosis and light chain deposition disease. Nephronectin was stained weakly in sclerotic lesions, such as focal segmental glomerulosclerosis and hypertensive nephropathy. The percentage of nephronectin-positive areas in the glomeruli from DN patients [15.1 ± 4.7% (n = 18)] was significantly higher than that for other kidney diseases [5.5 ± 3.6% (n = 172)] (p < 0.001). In multiple regression analyses, fasting plasma glucose and hemoglobin A1c were significantly associated with the increase in the percentage of nephronectin-positive areas in the glomeruli (β = 0.23, p < 0.001 and β = 0.16, p = 0.045, respectively). The expression of nephronectin was sufficient to discriminate DN from other kidney diseases with mesangial matrix expansion and nodular lesions. We consider that nephronectin staining could be helpful in the diagnosis of DN.