Monocyte chemoattractant protein-1 (MCP-1) is a prognostic biomarker and a therapeutic target in diabetic nephropathy

Abstract

Diabetic nephropathy is the common cause of kidney failure worldwide. Despite optimal use of inhibitors of reninangiotensin system (RAS), a significant proportion of diabetic patients developed progress kidney disease. Novel mechanistic biomarker will be beneficial in identifying patients with high risk of progression.MCP-1 (also known as CCL2) is a potent chemokine for monocytes and macrophages. Increased amount of urinary MCP-1 were detected in urine from patients with diabetic nephropathy. Earlier work from our laboratory showed that urinary MCP-1/creatinine ratio is prognostic of the rate progression (loss in estimated glomerular filtration rate (eGFR)) over 6 years prospective follow up. Recently, the prognostic values of urinary MCP-1 in diabetic nephropathy have been validated by other research groups.Multiple mechanisms, including high concentration of glucose, may contribute increased synthesis of MCP-1 by glomerular mesangial cells. Our recent work also showed that stimulation of P2X7 receptor with extracellular ATP synergized with high concentration of glucose in mesangial cell production of MCP-1.The receptor for MCP-1 has been targeted in a recent clinical trial in diabetic nephropathy. Furthermore, P2X7 receptor may also be a novel therapeutic target in diabetic nephropathy. In conclusion, MCP-1 is both a prognostic biomarker and a therapeutic target in diabetic nephropathy.