Uraemic pruritus: clinical characteristics, pathophysiology and treatment

Pruritus is a common complication of end-stage renal disease (ESRD), affecting about one-third of dialysis patients. It is a chronic, unpleasant symptom with a strong negative impact on patients' quality of life, often inducing sleeplessness and mood disorders. Recent data show that it is also associated with increased mortality. The pathogenesis of uraemic pruritus (UP) is multifactorial. Triggering factors may include uraemia-related abnormalities (particularly involving calcium, phosphorus and parathyroid hormone metabolism), accumulation of uraemic toxins, systemic inflammation, cutaneous xerosis, and common co-morbidities such as diabetes mellitus and viral hepatitis. Recent findings suggest that the neurophysiology of itch is similar to that of pain; this has led to the hypothesis that the two phenomena also closely interact in ESRD patients, who often also experience uraemic neuropathy. The management of UP needs to address several different issues, such as optimization of dialysis efficacy and skin hydration, and correction of calcium-phosphorus metabolism abnormalities. A wide range of antipruritic drugs have been suggested for the treatment of UP, although most of them have only been tested in small, uncontrolled trials, which have yielded conflicting results. Antihistamines are now known to have little or no efficacy, although they are still often prescribed. Novel neurotropic drugs such as gabapentin, along with opioid receptor modulators such as nalfurafine, appear to be effective and well tolerated, but their efficacy has not yet been directly compared. Finally, physical therapies, including UV radiation, may also have a role in patients with refractory symptoms.