TY - JOUR
T1 - Association of urinary biomarkers of inflammation, injury, and fibrosis with renal function decline
T2 - The ACCORD trial
AU - Nadkarni, Girish N.
AU - Rao, Veena
AU - Ismail-Beigi, Faramarz
AU - Fonseca, Vivian A.
AU - Shah, Sudhir V.
AU - Simonson, Michael S.
AU - Cantley, Lloyd
AU - Devarajan, Prasad
AU - Parikh, Chirag R.
AU - Coca, Steven G.
N1 - Funding Information:
G.N.N. is supported, in part, by National Institutes of Health (NIH) grant T32-DK007757. C.R.P. is supported by NIH grant K24- DK090203 and NIH P30-DK079310-07 O’Brien Center Grant. C.R.P and S.G.C are supported, in part, by Chronic Kidney Disease Biomarker Consortium grant 1U01DK106962-01. This research was supported by National Institute of Diabetes Digestive and Kidney Diseases grant R01DK096549 (to S.G.C.). The Action to Control Cardiovascular Disease Trialwas supported by contracts 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, and IAA-Y1-HC-1010 from the National Heart, Lung, and Blood Institute; other components of the NIH, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; the Centers for Disease Control and Prevention; and General Clinical Research Centers. C.R.P. is a named coinventor on the IL-18 patent.
Publisher Copyright:
© 2016 by the American Society of Nephrology.
PY - 2016
Y1 - 2016
N2 - 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 10ml/min per 1.73m2),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-tocreatinine 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. ConclusionsUrinarymonocyte chemotactic protein-1-to-creatinine ratio concentrationswere strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.
AB - 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 10ml/min per 1.73m2),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-tocreatinine 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. ConclusionsUrinarymonocyte chemotactic protein-1-to-creatinine ratio concentrationswere strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.
KW - Biomarkers
KW - CCL2 protein, human
KW - CHI3L1 protein, human
KW - Diabetes Mellitus, Type 2
KW - Follow-Up Studies
KW - Inflammation
KW - albuminuria
KW - chronic kidney disease
KW - renal fibrosis
KW - renal injury
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U2 - 10.2215/CJN.12051115
DO - 10.2215/CJN.12051115
M3 - Article
C2 - 27189318
AN - SCOPUS:85013363342
SN - 1555-9041
VL - 11
SP - 1343
EP - 1352
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 8
ER -