The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease

Glomerular-derived proteins may activate tubular cells to express the macrophage-directed chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Macrophages at interstitial sites have a central role in directing renal scarring. We have prospectively assessed the relationship between albuminuria, urinary MCP-1/CCL2, interstitial macrophage infiltration, in situ damage, and clinical outcomes in a large group of patients with chronic kidney disease. We studied 215 patients and quantified albumin-creatinine ratio (ACR), urinary MCP-1/CCL2, interstitial macrophage numbers, and in situ damage. ACR correlated with urinary MCP-1/CCL2 (correlation 0.499; P<0.001), interstitial macrophage numbers (correlation 0.481; P<0.001), and index of chronic damage (correlation 0.363; P<0.001). Macrophage numbers closely correlated with in situ damage (correlation 0.755; P<0.001). By multivariate analysis ACR, urinary MCP-1/CCL2, and interstitial macrophage numbers were interdependent. By Kaplan-Meier survival analysis albuminuria, urinary MCP-1/CCL2, interstitial macrophages, and chronic damage predict the outcome. ACR, macrophage numbers, chronic damage, and creatinine independently predicted renal survival. The association of ACR with other variables was strongest in patients with less advanced disease states. There is a close association between albuminuria, urinary MCP-1/CCL2, and interstitial macrophage infiltration with in situ damage and clinical outcomes. These findings support the hypothesis that albuminuria triggers tubular MCP-1/CCL2 expression with subsequent macrophage infiltration. These processes may represent the dominant pathway for the progression of renal injury before the establishment of advanced renal scarring.