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

Abstract

Reliable biomarkers are needed to identify patients with glomerular disease at risk of progression. Transforming growth factor beta 1 (TGF-β1) 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. 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-β1, standardized to urinary creatinine. The initial estimated glomerular filtration rate, proteinuria and rate of renal function decline (slope) were 36 ml/min per 1.73 m2, 1.1 g/day and -4.0 ± 7.2 ml/ min per 1.73 m2 year. Median urinary TGF-β1 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-β1 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 R2 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. Urinary MCP-1 is a marker of renal function decline in diabetic and nondiabetic proteinuric renal disease, independent of and additive to proteinuria.