**1. Introduction**

Pruritus is a nociceptive sensation transmitted centrally from the periphery by the unmyeli‐ nated, large, slowly conductive C fibers [1]. Pruritus is the dominant symptom of skin disease and a frequent manifestation of systemic disease. Of all of the systemic disorders, uremia is certainly the most important cause of pruritus [2]. The association between uremia and pruritus was first reported more than a century ago. Patients with severe chronic renal failure may be predisposed to the development of xerosis, hyperpigmentation, uremic roseola, calcinosis cutis, acquired perforating dermatosis, bullous dermatosis of hemodialysis, half and half nails and pruritus [3,4]. However, pruritus is often the most difficult to manage [5] and also related to mortality of end-stage renal disease (ESRD) patients. Aside from kidney transplantation, which is the only definitive treatment, therapeutic approaches for the treatment of pruritus have largely been empirical. The main goal of therapy remains to minimize the severity of pruritus and improve the quality of life, especially among those who are not transplantation candidates or are waiting for surgery.

Uremic pruritus (UP) may not be associated with the initiation of hemodialysis therapy, or symptoms may first become apparent with it [6]. A global study reported a 42% prevalence of moderate or extreme UP, which was strongly associated with sleep disturbance, depression, impaired quality of life and mortality [7]. Another study noted a higher percentage of pruritus in patients with more advanced chronic kidney disease (CKD): 18% of stage 3, 26% of stage 4, 42% of stage 5 and 58% of stage 5 CKD on maintenance hemodialysis for 1 month or greater [8] experienced UP. Once pruritus manifests itself, it often persists [6]. Pruritus can be a temporary condition lasting only a few months, but more commonly, it affects patients for more than 1 year. About one quarter of patients suffer from it only during or soon after hemodialysis, whereas others find this period a time of pruritus symptomatic exacerbation [9,10]. The intensity of pruritus was described as mild in 22- 52.6%, moderate in 22.6- 40% and

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

severe in 8- 40% of patients [10-12]. About half of UP patients suffer from continuous itch, while the others experience it only occasionally with episodes of exacerbation. UP affects quality of life because of serious discomfort, anxiety, depression and sleeping disorders, especially because it is usually worse at night [13]. Pruritus may increase in intensity during the summer months, possibly due to the rising skin temperature reducing the threshold for the perception of UP, as occurs in other types of pruritus [14]. For that reason, external heat, sweat and stress can aggravate UP, and cold or hot showers can alleviate the symptoms [15]. The skin may appear normal or display different types of lesions, mostly related to scratching (e.g., lichen simplex, prurigo nodularis or keratosis papules) [13].

UP may be localized or generalized. Generalized itching is evident in about half of the patients [6]. Pruritus in dialysis patients is most commonly localized to the back, followed by the forearm with an arterio-venous fistula (perhaps due to frequent washing and traumatization of this region), abdomen, or head [16]. It has been reported that patient age, sex, underlying renal disease or dialysate solution used for hemodialysis (bicarbonate-based or acetate-based) have no influence on UP [6,10]. However, using less permeable and less biocompatible dialysis membranes show higher incidence of pruritus [6,10]. Moreover, patients with longer period of hemodialysis (> 3 months) may have high tendency to experience UP [13], possibly due to the accumulation of undefined pruritogenic cytokines or other substances [10].

Different scoring systems were used to quantify the severity of UP in clinical trials. The most commonly used include the visual analogue score (VAS) [17-19], a 4-point pruritus score [20] and a comprehensive validated questionnaire that was developed based on a short form of the McGill pain questionnaire [17,21]. This questionnaire was found to be reliable and provided valid data on the sensory, affective and overall intensity of UP and may provide a basis for future cross-cultural studies of itching [17] and for other study-specific scales [22].

Clinical appearance of UP can be observed by secondary changes such as atrophy of adnexal structures, microangiopathy with necrosis of endothelial cells, changes of sebaceous glands, lesions or lichen complex chronicus, excoriations and prurigo nodularis [23]. Although hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) seem to be associated with a similar incidence of UP [24,25], some have found its incidence with CAPD was 10% [4] to 14% [26] lower, possibly due to a more effective elimination of possible pruritogenic substances by the peritoneum than by artificial membranes [27].

Due to the effect of UP which can cause serious discomfort, severe anxiety or even depression andsleepingdisorders,itreallyaffectpatients'qualityoflife.Sincesleepingdisordersarerelated tochronicfatigue,ithas stronginfluenceonmentalandphysicalhealthofpatients [15].Recently, studies demonstrated an association between UP and an increased risk of mortality [7,19].
