New Option for Dry, Itchy Skin in End-Stage Kidney Disease

Marcia Frellick

March 31, 2020

Opioid receptor modulators might be key to the treatment of pruritus in hemodialysis patients with end-stage kidney disease, results from a new phase 3 study show.

Research on pruritus in this population has been scant, and studies have been underwhelming, with small sample sizes, various methodologies, and a high risk for bias, said Holly Koncicki, MD, assistant professor of nephrology at the Icahn School of Medicine at Mount Sinai in New York City.

But a new double-blind, randomized trial showed itch-related quality of life was significantly better with the opioid receptor modulator difelikefalin (Korsuva, Cara Therapeutics) than with placebo in patients undergoing hemodialysis.

A decrease of at least 3 points on the 10-point Worst Itching Intensity Numerical Rating Scale (WI-NRS) was achieved by more patients in the difelikefalin group than in the placebo group (49.1% vs 27.9%; < .001).

The benefit was apparent at week 1 and was maintained out to week 12, Koncicki, who was not involved with the study, reported during a virtual session at the virtual National Kidney Foundation 2020 Spring Clinical Meetings.

"In the future, I think our treatment for pruritus is really going to be with the opioid receptor modulators," she said during her presentation.

The study, funded by Cara Therapeutics, shows that difelikefalin does not cross the blood–brain barrier, she said in response to an audience question.

"The molecular structure of it should preclude it from passing. When they looked for evidence that it was passing through, like dysphoria or hallucination, that was not seen," she explained.

Alternative to Antihistamines

Substitutes are needed to antihistamines, which are not recommended but still widely prescribed, Koncicki pointed out.

In fact, antihistamines are by far the most widely prescribed first-line medicines for pruritus associated with chronic kidney disease, according to an analysis of data on 35,452 patients on hemodialysis in 17 countries, who were part of the Dialysis Outcomes and Practice Patterns Study (DOPPS).

The benefits of antihistamines are related more to sedation than to treatment of the underlying mechanism, said Koncicki. And adverse effects include dizziness, drowsiness, and confusion, which are particularly concerning in patients who might already be taking many other medications.

The other medications commonly used are gabapentin or pregabalin, which have some evidence of efficacy, but concerns have been raised about dose-dependent risks for altered mental status, falls, and fractures, she noted.

Table. Worldwide Use of Medications for Pruritis Associated With Chronic Kidney Disease
Medication First-Line, Chronic Use, % "I Never Prescribe", %
Oral antihistamines 78 38
Topical antihistamines 23 36
Topical corticosteroids 9 29
Gabapentin 5 52
Source: Clin J Am Soc Nephrol. 2017;12:2000-2007.

Dry skin is prevalent in 85% of hemodialysis or peritoneal dialysis patients. "Whether this is the cause of the itching or exacerbates the condition is unclear," Koncicki said.

Topical therapies, such as petroleum jelly and baby oil, should be the foundation to treatment. Although the evidence is weak, these products have been shown to relieve dry skin and severity of itch and increase quality of life, she said.

The risk that accompanies these emollients is minimal, so Koncicki said she recommends them as initial therapy. But for patients who don't respond to emollients or medication, she recommends alternative therapies, such as acupuncture and ultraviolet B light.

Itch Second Only to Fatigue

Studies have shown that patients on dialysis with end-stage kidney disease report that pruritus is the second most common symptom, behind fatigue, said Joao Pedro Teixeira, MD, from the University of New Mexico School of Medicine in Albuquerque.

About 50% to 70% of patients experience it, he reported during his presentation.

Approximately 18% of hemodialysis patients around the world have moderate to extreme chronic pruritus, but about 18% of patients in that group "get no treatment whatsoever for their pruritus," Teixeira said, citing data from the DOPPS analysis.

In fact, most patients are reluctant to tell a clinician that they are experiencing itchiness. Fewer than half told their care team. In that group, patients were most likely to tell their nephrologist (42%), followed by a nurse or other staff (32%), dermatologist (18%), and primary care doctor (16%).

Additionally, 69% of the medical directors participating in DOPPS underestimated the prevalence of pruritus in their dialysis facility.

There is also a high prevalence of pruritus in patients with chronic kidney disease who are not on dialysis. Moderate to severe itching was reported by 24% of such patients in one study, Teixeira said.

The data show that itching is most prevalent in older patients, women, and in those with stage 5 chronic kidney disease, lung disease, diabetes, or physician-diagnosed depression, he added.

National Kidney Foundation (NKF) 2020 Spring Clinical Meetings. Presented March 27, 2020.

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