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Abstract: FR-PO433

The Predictive Role of Serum MRP8/14 (S100A8/A9) on Mortality in Hemodialysis Patients

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Kanki, Tomoko, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Kuwabara, Takashige, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Morinaga, Jun, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Fukami, Hirotaka, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Umemoto, Shuro, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Fujimoto, Daisuke, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Mizumoto, Teruhiko, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Hayata, Manabu, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Kakizoe, Yutaka, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Izumi, Yuichiro, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Mukoyama, Masashi, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
Background

The inflammatory mediator myeloid-related protein 8 (MRP8: S100A8), which forms a heterodimeric complex with a binding partner MRP14 in the bloodstream, plays important roles as an endogenous ligand in various diseases. Serum MRP8/14 reportedly became a potential biomarker in patients with acute coronary syndrome and ANCA-associated vasculitis. The aim of this study was to investigate the predictive role of serum MRP8/14 levels on all-cause mortality in hemodialysis patients.

Methods

We conducted a multicenter, observational cohort study of 388 Japanese subjects undergoing maintenance hemodialysis in Kumamoto, Japan. Serum MRP8/14 levels were measured using an ELISA. The potential associations between serum MRP8/14 levels and clinical variables were examined in a cross-sectional study. Multivariable Cox regression was used to estimate the association between serum MRP8/14 levels and mortality, adjusting for possible confounding variables including age, sex, diabetes and others. Median follow-up was 6.6 years.

Results

The mean age of the subjects was 65.3 years, 36.9% were female, and the median vintage was 5.8 years. The median MRP8/14 level was 6108 ng/ml [normal range in healthy subjects: 500–3500] at baseline. Serum MRP8/14 levels positively correlated with white blood cells (ρ=0.54, P<0.0001) and high-sensitivity C reactive protein (hs-CRP) values (ρ=0.34, P<0.0001). We classified MRP8/14 and hs-CRP into tertile, and estimated the hazard ratios (HR) for all-cause mortality in comparison with the lowest tertile. As for hs-CRP, the middle tertile (HR, 1.90; 95%CI, 1.04–3.61) and the highest tertile (2.87; 1.54–5.54) were each significantly associated with all-cause mortality in the low-phosphate group (cut-off, 6.0 mg/dl), after adjustment for relevant confounding factors. In contrast, elevated MRP8/14 levels were evidently associated with all-cause mortality in the middle tertile (12.3; 1.64–271.6) and in the highest tertile (26.8; 3.49–610.4) in the high-phosphate group, but not in the low-phosphate group.

Conclusion

High serum MRP8/14 levels should give a potential predictive marker on mortality in hemodialysis patients with high-phosphate levels, which characteristic differs significantly from that of a conventional inflammatory marker, hs-CRP.