• Girish N Nadkarni, Veena Rao, Faramarz Ismail-Beigi, Vivian A Fonseca, Sudhir V Shah, Michael S Simonson, Lloyd Cantley, Prasad Devarajan, Chirag R Parikh, and Steven G Coca.
• Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York;
• Clin J Am Soc Nephrol. 2016 Aug 8; 11 (8): 1343-52.

Background And ObjectivesCurrent measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome.Design, Setting, Participants, & MeasurementsWe used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression.ResultsBaseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio.ConclusionsUrinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.Copyright © 2016 by the American Society of Nephrology.

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