Epidermal Proteinase-Activated Receptor-2 Expression is Increased in End-Stage Renal Disease Patients with Pruritus: A Pilot Study

Uremic pruritus is a common problem in patients with end-stage renal disease (ESRD), but the underlying mechanisms are not yet fully understood. We aimed to investigate the association between severity of uremic pruritus and cutaneous serine protease activity, as well as proteinase-activated receptor-2 (PAR-2) expression. Twelve ESRD patients with pruritus, 4 ESRD patients without pruritus, and 6 healthy controls were enrolled. Skin biopsies were obtained from the abdomen. Protease activity and PAR-2 expression in the epidermis were examined by in situ zymography and confocal laser microscopy, respectively. All ESRD patients presented more pronounced cutaneous protease activity compared with that in healthy controls. The skin samples from the patients with pruritus showed higher protease activity than either nonpruritic ESRD patients or healthy controls. The epidermis in all samples of ESRD patients presented higher immunoreactivity against PAR-2 versus those of healthy controls. In addition, correlation analysis between PAR-2 expression and VAS pruritus scores showed a significant positive correlation. Our data suggests that levels of serine protease and PAR-2 expression could play important roles in the pathogenesis of uremic pruritus.