1. ¹Department of Nephrology, Queen Elizabeth Hospital, Birmingham, UK
2. ²Department of Biological Sciences, University of Warwick, Warwick, UK
3. ³Department of Clinical Endocrinology, Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Berlin, Germany
4. ⁴Department of Renal Immunobiology, University of Birmingham, Birmingham, UK
5. ⁵Department of Pathology, University of Birmingham, Birmingham, UK

Correspondence: P Cockwell, Department of Nephrology, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. E-mail: paul.cockwell@uhb.nhs.uk

Received 12 June 2005; Revised 8 October 2005; Accepted 28 October 2005; Published online 15 February 2006.

Abstract

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