Monocyte chemoattractant protein-1 levels in patients with glomerular disease

Abstract

Chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 have been implicated in recruiting leukocytes to the glomerulus during immune renal injury. To detect the expression of MCP-1 in human glomerular disease, we measured urinary MCP-1 levels in patients with a variety of glomerulopathies. These data demonstrated that MCP-1 was present in the urine of patients with glomerular disease and that patients with inflammatory glomerulopathies had higher levels of urinary MCP-1. Urinary MCP-1 correlated with the extent of proteinuria ( r = 0.71, P < 0.0001), but not with serum MCP-1 levels ( r = 0.14, P > 0.3). The MCP-1 present in urine was biologically active, increasing monocyte migration in a microchemotaxis assay. This activity was attenuated by the addition of anti-MCP-1 antibody to the samples. Enumerating glomerular macrophages demonstrated that glomerular inflammation was correlated with urinary MCP-1 levels ( r = 0.53, P < 0.02). Individuals with light microscopic evidence of severe glomerular injury (ie, crescents, necrosis, endocapillary proliferation) had significantly higher levels of MCP-1 in their urine than patients with less severe glomerular changes (1,962 ± 612 pg MCP-1/mg creatinine v 314 ± 45 pg MCP-1/mg creatinine; P < 0.002). Taken together, these results suggest that urinary MCP-1 reflects the extent to which MCP-1 that is produced in the glomerulus participates in the glomerular inflammatory response.