Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy: A prospective study

Aims: The evolution of diabetic nephropathy is incompletely accounted by current clinical tools. New biomarkers may refine patient assessment and help monitor therapy. We compared the added predictive value of 7 candidate inflammatory urinary biomarkers to known risk factors of progression. Methods: We prospectively followed 83 patients with overt diabetic nephropathy for a median 2.1 years and obtained repeated measurements of proteinuria, IL-1 beta, IL-6, IL-8, MCP-1, TNF-alpha, TGF-beta 1, and PAI-1. Results: Patients had an initial estimated glomerular filtration rate of 25 +/- 9 mL/min/1.73 m(2), blood pressure of 142/69 mmHg and used a median of 4 anti-hypertensive medications over the course of the study. The observed rate of renal function decline was 2.9 +/- 3.0 mL/min/1.73 m(2)/year. All urinary biomarkers levels were collinear and for each one except IL-1 beta, elevated levels predicted a more rapid progression. MCP-1 was the only biomarker increasing during follow-up, which also correlated with a worst outcome. Using multivariate linear regression adjusting for clinical risk factors of progression, urinary MCP1 and TGF-beta 1 predicted progression independently and additively to the degree of proteinuria. We dichotomized these 3 biomarkers and observed a renal function decline with 0, 1, 2 or 3 elevated biomarkers of -0.8 +/- 1.4, -2.1 +/- 2.1, -4.2 +/- 2.8 and -6.0 +/- 2.8 mL/min/1.73 m(2)/year, respectively (p < 0.001). Conclusions: Multiple urinary biomarkers predict outcome in overt diabetic nephropathy. However, urinary MCP-1 and TGF-beta 1 are also independent and additive to proteinuria in predicting the rate of renal function decline and could serve as useful clinical tools in patient risk stratification. (C) 2013 Elsevier Ireland Ltd. All rights reserved.