Patients with end-stage kidney disease on hemodialysis can have many different symptoms that affect their quality of life.  While seeing patients in the dialysis unit, I often see many similar symptom complaints from patients.  Complaints from patients on hemodialysis include post-dialysis fatigue (need to take a nap after dialysis, no energy to run errands, etc.), muscle cramps (at night, right after   dialysis), and pruritus.  Pruritus is the medical term for itchy skin that can affect the quality of life of a person. The pathophysiology of chronic kidney disease-associated pruritus (also known as hemodialysis-associated pruritus or uremic pruritus) is thought to be multifactorial: a combination of demographic, biologic, neuropathic, and psychogenic factors.  One theory suggest interleukin-1 as a biological causes of pruritus.  The pruritus is often worse at night and affects sleep quality in these patients. 

 Daraghmeh et al. published a cross-sectional study examining pruritus and sleep problems among hemodialysis patients in four different centers in Palestine.  Using the 5-D itching score for pruritis and the Pittsburgh Sleep Quality Index (PSQI) score for sleep disturbances.  Of the 250 participants, there were 121 with complaints of pruritus and 21% patients with severe symptoms.  About 66% were classified as poor sleepers on the PSQI.  Regression analysis showed that the 5-D itching score and the total number of comorbidities were significantly associated with the PSQI score, demonstrating that poor sleep quality is often due to pruritus. 

A prior publication by Orasan et al. found that pruritus and poor sleep quality can significantly affect survival in this population.  Survival differences were found in the 170 patients treated with hemodialysis or hemodiafiltration subdivided as having  both pruritus/insomnia, pruritus alone, insomnia alone, or neither symptom.  Survival at 20 months was lower in those patients with both pruritus and insomnia, highlighting that these symptoms are beyond a minor annoyance. 

Takahashi et al. reported on development of a treatment algorithm using topical medications for pruritus that has shown effective results.  The proportion of patients with pruritus decreased significantly from 96.6% in 2009 to 66.8% in 2018 with the use of this algorithm.  The algorithm consisted of treatment with moisturizers alone; moisturizer and topical steroids; moisturizer, topical steroids and Nalfurafine; and moisturizer and Nalfurafine.  Nalfurafine, which can be intravenous or orally administered, is a kappa opioid receptor agonist but unfortunately it is not available in the all countries.  A newer agent,  Difelikefalin, also a kappa opioid receptor agonist is showing promise.  This medication is administered into the venous line of the dialysis circuit at each hemodialysis session. 

Use of moisturizers applied several times a day is an important part of pruritus treatment. If there is no relief, adding a topical steroid or the addition of antihistamines, or agents to address neuropathy such as gabapentin or pregabalin are potential next steps.  With the emergence of new medications like Difelikefalin this opens the door to some potentially better treatment algorithms. 

The incessant itching does not just effect our patient’s quality of life but also their risk of survival. What is your treatment algorithm for chronic kidney disease-associated pruritus?

- Dr. Daphne Knicely

BMC Nephrology