Urinary monocyte chemotactic protein 1: marker of renal function decline in diabetic and nondiabetic proteinuric renal disease

Background: Reliable biomarkers are needed to identify patients with glomerular disease at risk of progression. Transforming growth factor beta 1 (TGF-beta 1) and monocyte chemotactic protein 1 (MCP-1) play key roles in promoting renal tissue injury. Whether their urinary measurement adds value to current predictors of progression is uncertain. Methods: We enrolled patients with diabetic (n=53) and nondiabetic (n=47) proteinuric renal disease and retrospectively studied their rate of renal function decline over a defined period of 2 years. We simultaneously measured urinary protein, MCP-1 and TGF-beta 1, standardized to urinary creatinine. Results: The initial estimated glomerular filtration rate, proteinuria and rate of renal function decline (slope) were 36 ml/min per 1.73 m(2), 1.1 g/day and -4.0 +/- 7.2 ml/min per 1.73 m(2) year. Median urinary TGF-beta 1 and MCP-1 levels were 0.3 (range 0.0-28.1) and 18 (range 3-370) ng/mmol of creatinine, respectively. Urinary protein and MCP-1 to creatinine ratios were associated with slope, and this applied to both diabetic and nondiabetic patients separately. Urinary TGF-beta 1 showed no relation to slope. However, the majority of its measurements were below the suggested reproducibility threshold. Using linear regression, both normalized urinary protein and MCP-1 were independently associated with the slope. Adding urinary MCP-1 to the model statistically raised the adjusted R-2 from 0.35 to 0.40, refining patient risk stratification. Using cutoffs for urinary protein and MCP-1 obtained by receiver operating characteristic curves, the risk of progression was confidently determined in 80% of patients. Conclusion: Urinary MCP-1 is a marker of renal function decline in diabetic and nondiabetic proteinuric renal disease, independent of and additive to proteinuria.