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Dr. Giovambattista Virga

Nephrology and Dialysis Unit, Camposampiero (Padova), Italy



Pruritus is an unpleasant cutaneous sensation prompting a desire to scratch. It is a common and disturbing symptom among patients (pts) receiving hemodialysis (HD). The percentage of HD pts suffering from pruritus varies reportedly from 50% to 90% [1,2,3,4,5,6,7]. Interestingly, pruritus is typically not seen in acute renal failure [8].


Itch is transmitted by dedicated C neurons and the proximity of dermal mast cells to afferent C neurons has suggested a functional relation between these two cell types: mast cell activation releases tryptase, which activates a receptor localised on C fibre nerve terminals that transmit the itching sensation to the central nervous system. Additionally, receptor activation will lead to a local release of substance P that activates dermal mast cells, resulting in an increased release of TNF- which in turn sensitises nociceptor nerve terminals and enhances their responsiveness [9]. Substance P, a neurotransmitter widely distributed in the afferent sensory neurons, can communicate pain and some itching sensations from the periphery to the central nervous system and is considered potentially responsible for itching [10,11]. It is a potent vasodilator and may serve as a mediator for axon reflex vasodilatation [12].


The degree of itching is scored according to severity, frequency and distribution. The system proposed by Duo [13], modified by Mettang [14] and again by Hiroshige [3] is as follows:

scores for severity:

  • score 1: itching prompting no scratching
  • score 2: itching requiring scratching but without excoriations
  • score 3: itching demanding interminable scratching or accompanied by excoriations
  • score 4: itching causing total restlessness;

scores for distribution:

  • score 1: itching at a single location
  • score 2: scattered itching
  • score 3: generalised itching;

scores for frequency:

  • score: for every four short episodes (<10 minutes each) or one long episode (>10 minutes) of itching receives 1 point, up to a maximum of 4 points.

Other subjective evaluation methods are reported, based on intensity (absent, moderate, severe) and frequency (absent, occasionally, every day) [7]. Many studies have simply divided patients according to the presence or absence of itching [3,15,16,17].


In the uraemic population pruritus is often benign but serious complications have been described, such as greater irritability, skin excoriations (Fig. 1), sleep deprivation, depression, lower quality of life, and even suicide [18].


Many different metabolic disorders frequently associated with uraemia have been thought to be involved in the onset of pruritus in HD, but its aetiology still remains obscure.

Parathormone was initially accused of causing pruritus [19,20], but was subsequently found not guilty [3,4,5,15,21,22,23,24]. The theory of an altered bivalent ion metabolism, i.e. hypercalcaemia and hyperphosphoraemia [19,20,21], was not confirmed [3,4,5,7,15,22,23,24]. Hypermagnesaemia was also suggested as a potential culprit [25] without any subsequent confirmation [22].

A relationship between dialysis adequacy and pruritus has been suggested in some studies [3,5,26] and rejected in others [4,7,23,27].

Patients who are dialysed with less permeable and less biocompatible membranes are more likely to have pruritus than those using more permeable polysulfone types [28]. Dermatological studies have demonstrated that an intradermal injection of complement activation products or cytokines induces local itching [29,30,31] and complement activation and cytokine release are related to blood-membrane contact [32,33,34].

Numerous other agents have been considered responsible for uraemic pruritus, e.g. aluminium [15], vitamin A [35] (not confirmed [36]), histamine [16,37] (not confirmed [38]), serum bile acids [23] and clinical conditions, as well as xerosis of the skin [1,39] (not confirmed [40,41]), peripheral neuropathy [42] and iron-deficiency anaemia [43] (not confirmed [7]).

A role of opioid peptides has been suggested [44], but these findings have not been confirmed [45].

Interleukin-2 (IL-2), which is secreted by activated T helper cells type 1 (Th1), may be involved in the genesis of uraemic itch [46,47,48,49].

Inflammatory status has recently been found associated with pruritus in HD pts [7,17].

Inflammation markers such as transferrin and albumin were found significantly lower in HD pts affected by pruritus, while ferritin proved to be higher [7]. Additionally, serum C-reactive protein and interleukin-6 (IL-6) levels were significantly higher in HD pts with than in those without pruritus [17].

Potential culprits for pruritus in HD  
Parathormonenot confirmed
Hypercalcaemianot confirmed
Hyperphosphoraemianot confirmed
Hypermagnesaemianot confirmed
Iron-deficiency anaemianot confirmed
Dialysis inadequacy not confirmed
Xerosis of the skinnot confirmed
Vitamin A not confirmed
Histaminenot confirmed
Opioid peptidesnot confirmed
Aluminium overload 
Skin mast cells 
Peripheral neuropathy 
Substance P 
Bile acids 


The differential diagnosis of pruritus in HD patients includes neuropathic itches, such as occurs in postherpes neuralgia (simultaneously with pain) and the central neuropathic itch related to multiple sclerosis [9]. Cholestasis can induce severe pruritus and atopic eczema associated with psoriasis is a common dermatological cause of itching [9]. Many other conditions, e.g. diabetes, thyrotoxicosis, and malignant tumours, can also cause pruritus [50].


Just as the aetiology of uraemic pruritus is not fully understood, several therapies are used, none of which is entirely satisfactory. Antihistamines are often ineffective in uraemic pruritus.

Capsaicin, a natural alkaloid, used topically (0.025% cream), has proved effective in the treatment of HD-related pruritus [11,12,51]. It depletes and prevents the re-accumulation of substance P from local type C sensory nerve terminals [11,52].

Naltrexone, an opioid antagonist, has been found useful for a short-term amelioration of pruritus in HD patients, but it carries mild gastrointestinal side effects [44] so it should only be considered for severe pruritus.

By suppressing IL-2 production [46,48], drugs such as tacrolimus and thalidomide are quite effective in the treatment of itching in dialysis patients [47,49].

Non-pharmacological therapies include ultraviolet B phototherapy (which attenuates Th1 expression [53] and thereby relieves uraemic pruritus [54,55]) and electrical needle stimulation, that has been associated with encouraging results in uraemic patients [13].

Naltrexone [44]
Capsaicin [11,12,51]
Ultraviolet B[54,55]
Electrical needle[13]


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