P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS

Abstract

Abstract Background and Aims Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients. Method Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls. Results Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46, p<0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p<0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p<0.001). In a multivariate model including all univariate predictors (R2=61%, p<0.001) only ALP (β=0.70,p<0.001), CRP (β=0.49,p<0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p<0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p<0.001) (Figure 1). Conclusion Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.