Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

Abstract

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 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.

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.

• Authors: Girish N Nadkarni, Veena Rao, Faramarz Ismail-Beigi, Vivian A Fonseca, Sudhir V Shah, Michael S Simonson, Lloyd Cantley, Prasad Devarajan, Chirag R Parikh, Steven G Coca
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 11 Issue 8 Pg. 1343-1352 (08 08 2016) ISSN: 1555-905X [Electronic] United States
• PMID: 27189318 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Biomarkers
• CCL2 protein, human
• CHI3L1 protein, human
• Chemokine CCL2
• Chitinase-3-Like Protein 1
• HAVCR1 protein, human
• Hepatitis A Virus Cellular Receptor 1
• IL18 protein, human
• Interleukin-18
• Creatinine

Topics

• Aged
• Biomarkers (urine)
• Case-Control Studies
• Chemokine CCL2 (urine)
• Chitinase-3-Like Protein 1 (urine)
• Creatinine (urine)
• Diabetes Mellitus, Type 2 (physiopathology, urine)
• Diabetic Nephropathies (physiopathology, urine)
• Female
• Fibrosis
• Glomerular Filtration Rate
• Hepatitis A Virus Cellular Receptor 1 (metabolism)
• Humans
• Inflammation (urine)
• Interleukin-18 (urine)
• Male
• Middle Aged
• Randomized Controlled Trials as Topic