P1422CATHEPSIN-K IS A POWERFUL DIAGNOSTIC BIOMARKER IN PARATHYROIDECTOMIZED DIALYSIS PATIENTS

Abstract

Abstract Background and Aims Cathepsin-K (Cts-K) is a lysosomal cysteine protease mainly involved in bone remodeling and resorption. Although it is largely released by lung cells, osteoclasts and macrophages, increasing current evidence suggests that the parathyroids may somewhat regulate Cts-K balance. We therefore analyzed Cts-K in a cohort of 85 chronic HD patients (mean age 67+/-12, median dialysis vintage 3.2 yrs), also including some individuals who were previously parathyroidectomized. Method Cts-K serum levels were measured before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects matched for age and gender served as controls. Patients were further stratified according to whether they were parathyroidectomized or not. Results Cts-K levels were statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p<0.0001) and significantly associated with ALP (r=0.50, p<0.001), CRP (r=0.46,p<0.001) and PTH (r=0.24,p=0.02). Patients with previous parathyroidectomy (n=8) had significantly lower levels of Cts-K (942.3 vs 46.2 pg/mL, p<0.0001). At ROC analyses, Cts-K showed an excellent diagnostic profile in distinguishing parathyroidectomized patients (AUC 0.977, best Cts-K cutoff< 100 pg/mL; sens. 100%, spec. 93%; Figure 1). Of note, although slightly inferior, the AUC of Cts-K was not statistically different to that of PTH (p=0.11 for comparison of ROC curves). Conclusion Cathepsin-K may represent a potential candidate biomarker for diagnosing and managing MBD complications, particularly those related to parathyroid dysfunction. Its exact biological role in these conditions deserves further examination.