Electrolyte Blood Press.  2014 Dec;12(2):74-79. 10.5049/EBP.2014.12.2.74.

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

• Moon SJ
• Kim HJ
• Cho SB
• Lee SH
• Choi HY
• Park HC
• Ha SK

• KMID: 2052334
• DOI: http://doi.org/10.5049/EBP.2014.12.2.74

Abstract

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.

Keyword

End-stage renal disease; Pruritus; Proteinase activated receptor-2; Serine protease; Uremia

MeSH Terms

Abdomen
Biopsy
Epidermis
Humans
Kidney Failure, Chronic*
Microscopy, Confocal
Pilot Projects*
Pruritus*
Serine Proteases
Skin
Uremia
Serine Proteases

Figure

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  Fig. 1 Computer-based fluorescence intensity analyses. Comparison of serine protease activity was done in healthy controls (n=6), nonpruritic ESRD patients (n=4), and uremic pruritus patients (n=12). *p<0.01, **p< 0.001.

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  Fig. 2 Confocal laser microscopic study of epidermal PAR-2 expression. The skin samples obtained from (A) healthy controls, (B) nonpruritic ESRD patients, and (C) uremic pruritus patients indicate there was higher PAR-2 expression in uremic pruritus patients than in healthy controls or nonpruritic ESRD patients (original magnification ¡¿400, Bars=100 µm). (D) Computer-based relative fluorescence intensity analyses of PAR-2 expression in the entire epidermis and the upper half of epidermis were done in healthy controls (n=6), nonpruritic ESRD patients (n=4), and uremic pruritus patients (n=12). *p<0.01, **p<0.001.

• 

  Fig. 3 The correlation analysis between epidermal proteinase-activated receptor-2 expression and visual analogue scale of pruritus. Correlation analysis showed a significant positive correlation (spearman's rho=0.670; p=0.005).

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