SUN-181 HIGH SERUM CALPROTECTIN LEVELS MAY PREDICT MORTALITY RISK IN HEMODIALYSIS PATIENTS WITH HIGH-PHOSPHATE CONDITIONS

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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 for toll-like receptor 4, contributing to pathophysiology in various inflammatory diseases. Serum MRP8/14, known as calprotectin (CPT), reportedly became a potential biomarker in inflammatory diseases such as rheumatoid arthritis or ANCA-associated vasculitis, though there is no report in hemodialysis patients. The aim of this study is to investigate the predictive role of serum CPT on mortality in hemodialysis patients. We conducted a multicenter, observational cohort study of 388 Japanese subjects undergoing maintenance hemodialysis in Kumamoto, Japan. Serum CPT levels were measured using an ELISA. The potential associations between serum CPT levels and clinical variables were examined in a cross-sectional study. Multivariable Cox regression was used to estimate the association between serum CPT, high-sensitivity C reactive protein (hs-CRP), white blood cell (WBC) count and mortality, adjusting for possible confounding variables including age, sex, diabetes and others. A median follow-up period was 6.6 years. The mean age of the subjects was 65.3 years; 36.9% were female, and the median vintage was 5.8 years. The median CPT level was 6,108 ng/ml (median in healthy subjects, 2,800) at baseline. The serum CPT levels positively correlated with WBC count (ρ=0.54, P<0.0001) and hs-CRP values (ρ=0.34, P<0.0001). We classified serum CPT and hs-CRP into tertile, and estimated the hazard ratios (HRs) for all-cause mortality in comparison with the lowest tertile. In crude analysis, hs-CRP was an independent predictor of all-cause mortality after adjusting confounding factors (middle vs. low: HR, 2.01; 95% confidence interval [CI], 1.19–3.48 and high vs. low: HR, 2.92; 95% CI, 1.72–5.09). In the analysis by stratum of phosphate levels, as for hs-CRP, the middle tertile (HR, 1.94; 95%CI, 1.07–3.67) and the highest tertile (HR, 2.92; 95%CI, 1.58–5.63) 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 serum CPT levels were significantly associated with all-cause mortality in the highest tertile (HR, 14.7; 95%CI, 2.57–277.8) among the high-phosphate group, but not among the low-phosphate group. High serum CPT levels could 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.