Association of urinary biomarkers of inflammation, injury, and fibrosis with renal function decline: The ACCORD trial

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

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1343-1352
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume11
Issue number8
DOIs
StatePublished - 2016

Keywords

  • Biomarkers
  • CCL2 protein, human
  • CHI3L1 protein, human
  • Diabetes Mellitus, Type 2
  • Follow-Up Studies
  • Inflammation
  • albuminuria
  • chronic kidney disease
  • renal fibrosis
  • renal injury

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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