Journal
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 11, Issue 8, Pages 1343-1352Publisher
AMER SOC NEPHROLOGY
DOI: 10.2215/CJN.12051115
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Funding
- National Institutes of Health (NIH) [T32-DK007757]
- NIH [K24-DK090203, P30-DK079310-07]
- Chronic Kidney Disease Biomarker Consortium [1U01DK106962-01]
- National Institute of Diabetes Digestive and Kidney Diseases [R01DK096549]
- National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010]
- NIH, National Institute of Diabetes and Digestive and Kidney Diseases
- NIH, National Institute on Aging
- NIH, National Eye Institute
- Centers for Disease Control and Prevention
- General Clinical Research Centers
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Background and objectives Current 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, & measurements We 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 mu g/mg, and baseline eGFR within 10ml/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. Results Baseline 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. Conclusions Urinary 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.
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