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Abstract: TH-PO243

Association of Urine Biomarkers of Tubule Health With Mortality in Patients With Diabetes and CKD

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Vasquez-Rios, George, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Katz, Ronit, University of Washington School of Medicine, Seattle, Washington, United States
  • Cushman, Mary, University of Vermont College of Medicine, Burlington, Vermont, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
  • Schrauben, Sarah J., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Greenberg, Jason Henry, Yale School of Medicine, New Haven, Connecticut, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
  • Gutierrez, Orlando M., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States

Group or Team Name

  • CKD Biomarkers Consortium
Background

Biomarkers of kidney tubular health are associated with the risk of kidney failure in individuals with chronic kidney disease (CKD) and diabetes, independently of other factors. Whether these biomarkers are also associated with mortality remains unclear.

Methods

Among 560 individuals with diabetes and an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2 randomly sampled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (47% male, 53% Black), we measured urine biomarkers in stored baseline visit samples: monocyte chemoattractant protein-1 [MCP-1], alpha-1-microglobulin [a1m], kidney injury molecule-1 [KIM-1], epidermal growth factor [EGF], chitinase-3-like protein 1 [YKL-40], and uromodulin [UMOD]. Associations of biomarkers with all-cause and cause-specific mortality were examined in Cox regression models, adjusted for age, sex, race, education, and urine creatinine to account for differences in tonicity, blood pressure, body mass index, smoking, coronary heart disease, stroke, eGFR, and urine albumin.

Results

The baseline mean (SD) age was 70 (9) years, mean (SD) eGFR was 40 (3) ml/min/1.73m2, and median [IQR] albumin-to-creatinine ratio was 33 [10,213] mg/g. Over a mean (SD) of 6 (3) years of follow-up, 310 participants died from causes adjudicated as cardiovascular (n=121), cancer (n=30), or other (n=159). In fully adjusted models, each 2-fold higher concentration of KIM-1 and YKL-40 was associated with a higher risk of all-cause mortality: hazard ratio (HR) 1.15, 95%CI 1.01,1.31 and 1.13, 95%CI 1.07,1.20, respectively. Higher UMOD was associated with a lower risk of cardiovascular death (HR 0.87, 95%CI 0.77,0.99), and higher MCP-1 was associated with a higher risk of cancer-related death (HR 1.52, 95%CI 1.05,2.18) in fully adjusted models. Finally, biomarkers associated with other causes of death in fully adjusted models included: KIM-1 (1.25, 95%CI 1.04,1.50), EGF (1.38, 95%CI 1.05,1.82), and YKL-40 (1.18, 95%CI 1.08,1.29).

Conclusion

Higher urine concentrations of KIM-1 and YKL-40 are associated with an increased risk of all-cause mortality over 6 years in individuals with diabetes and CKD independently of established risk factors, eGFR, and urine albumin.

Funding

  • NIDDK Support