Protein Z is reduced in chronic kidney disease and not elevated in patients on haemodialysis

Abstract

Protein Z (PZ) is a vitamin K dependent serine protease inhibitor, which along with its cofactor Protein Z-dependant protease inhibitor (ZPI) has anti-Xa activity. PZ has previously been reported to be elevated in patients with end-stage chronic kidney disease (CKD) on haemodialysis but not in non-dialysed CKD patients raising the possibility that PZ may have a role in the bleeding diathesis of patients on haemodyalisis. PZ was measured in controls (n = 18), CKD on haemodialysis (n = 23) and CKD not on dialysis (n = 23). Patients on vitamin K antagonists, with acute inflammatory conditions (as measured by CRP) or liver dysfunction were excluded PZ levels were reduced in CKD patients when compared to levels in the control group (1.35 mug/mL vs 1.80 respectively, p = 0.022). Subgroup analysis revealed a trend toward reduction in mean PZ in the CKD subgroups (non-dialysed CKD group 1.37 (p = 0.08); haemodialysis 1.33 (p = 0.12)). There were no significant differences in the PZ levels for different stages of non-dialysed CKD patients when stratified by the level of glomerular filtration rate (GFR). These data show that PZ levels were reduced in patients with CKD, and not elevated in patients on haemodialysis, arguing against a role for PZ in the bleeding diathesis of renal failure. This finding is in contradiction to a previous report which found PZ to be elevated in patients on haemodialysis.