Difelikefalin Research

Saucereau J, Brenaut E, Ficheux AS, Rostoker G, Misery L, Le Gall-Ianotto C et al.

Pruritus is a frequent and distressing symptom in chronic kidney disease (CKD). This study aimed to evaluate the association between pruritus and comorbidities or survival in CKD before the approval of difelikefalin (DFK), a novel treatment for CKD-associated pruritus (CKD-aP). A systematic liter...

Kljajić M, Parać E, Atić A, Bašić-Jukić N

Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifacto...

Wu S, Xu K, Chen D, Feng J, Xu B, Li N et al.

Opioid receptors, as members of the G-protein-coupled receptor (GPCR) superfamily, represent promising therapeutic targets for managing nociception. Herein, we designed, synthesized, and pharmacologically characterized the novel bifunctional decapeptide, MKOP002. In vitro, MKOP002 activated both ...

Naar L, Mussnig S, Niknam J, Brosch F, Krenn S, Mayer CC et al.

Chronic kidney disease–associated pruritus (CKD-aP) and depression are common but often underrecognized and undertreated in hemodialysis (HD) patients, lowering quality of life and worsening outcomes.To evaluate whether the systematic, repeated collection of patient-reported outcome measur...

Zhang X, Zhang S, Wu S, Xu B, Feng J, Hu X et al.

Recently, κ-opioid receptor (KOR) agonists have been attractive therapeutic candidates for the treatment of pain and pruritus. To advance the development of effective and safer peripherally restricted KOR agonists, we designed, synthesized, and evaluated 21 novel chimeric peptides incorpora...

Zhu S, Gao C, Yue Y

Chronic kidney disease-associated pruritus (CKD-aP) is one of the most prevalent and distressing symptoms experienced by patients with end-stage renal disease (ESRD), significantly impacting their quality of life and the sustainability of hemodialysis (HD) treatment. This systematic review aimed ...

Di Giovanni M, Piccinni CP, Tagliente F, Urciuolo F, Fulignati P, Bonerba B et al.

Chronic kidney disease-associated pruritus (CKD-aP) is a prevalent symptom in hemodialysis (HD) patients, negatively impacting quality of life and sleep. Difelikefalin, a selective κ-opioid receptor agonist, has shown efficacy in short-term trials. We hypothesized that Difelikefalin would d...

Burton JO, Grewal S, Schaufler T, Ruessmann D, Lowe M, Wen W et al.

Difelikefalin (DFK) is approved to treat chronic kidney disease-associated pruritus (CKD-aP) in adults undergoing maintenance hemodialysis. The influence of concomitant opioid use on DFK treatment outcomes remains uncertain.Exploratory analyses were conducted from the phase 3, placebo (PBO)-contr...

Rungkitwattanakul D, Brooks M, Adesina S, Belrhiti S, Chaijamorn W, Charoensareerat T et al.

Uremic pruritus is one of the most debilitating complications among patients with end-stage kidney disease (ESKD) receiving hemodialysis. For patients who are refractory to traditional therapies (topical analgesics, antihistamines, or gabapentinoids), the use of low-dose naltrexone can be an opti...

Rostoker G, Griuncelli M, Francisco S, Loridon C, Languille-Llitjos E, Boulahia G et al.

Iron overload by liver magnetic resonance imaging (MRI) is highly prevalent today in the hemodialysis population worldwide and is a controversial topic in the management of dialysis-related anemia, as iron deposits can be seen on MRI but without clinical consequences. The aim of this study was to...

Chen Z, Zhao J, Xiao N, Zhang F, Zhao S, Yin H et al.

Several studies have found that Small Ubiquitin-related Modifier (SUMO) exert therapeutic effects in heart failure (HF) by affecting different pathways, but the mechanisms of SUMO regulation in HF were unclear. The single sample gene set enrichment analysis (ssGSEA) and weighted gene co-expressio...

Latus J, Mayer G, Narvaez C, Manu M, Jesus S, Ruessmann D et al.

Chronic kidney disease-associated pruritus (CKD-aP) is a debilitating condition with limited treatment options. A managed access programme (MAP) began in October 2021 to provide early, controlled access to the novel antipruritic difelikefalin to European and Australian patients with CKD-aP with n...

Aucella F, Zerbi S, Monaco MP, Bonomini M, Alberici F, Losappio V et al.

Chronic kidney disease-associated pruritus (CKD-aP), defined as moderate to severe itching directly related to kidney disease, affects about one-third of haemodialysis patients and has been associated with poor quality of life, poor sleep, depression and increased mortality. Difelikefalin (DFK) i...

Wathanavasin W, Thammathiwat T, Susantitaphong P

Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is one of the most distressing symptoms of patients with CKD, adversely affecting their quality of life and survival. This study aimed to investigate the efficacy and safety of gamma-aminobutyric acid (GABA) analogues and opioid-based ther...

Cîrstea Ș, Orzan OA, Zilișteanu DS

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing symptom that affects both dialysis and non-dialysis patients, significantly impairing their quality of life. Despite its multifactorial pathophysiology, no gold-standard treatment has been established. This review explores vario...

Venugopal S, O'Hara DV, Agarwal N, Hole BD, Snead CM, Stallworthy E et al.

Chronic kidney disease-associated pruritus (CKDaP) is a distressing symptom affecting a significant proportion of people with advanced kidney disease. There are many studies of varying quality in the literature testing a wide variety of CKDaP therapies and no evidence-based consensus guidelines f...

Ständer S, Guttman-Yassky E, Yosipovitch G, Wiegmann H, Metze D, Kim M et al.

Prurigo nodularis (PN) is a severe, intensely pruritic subtype of chronic prurigo for which the molecular basis and interplay between pathophysiologic mechanisms and clinical manifestations are poorly understood.LOTUS-PN was a longitudinal observational study that included 54 participants from 11...

Takeuchi H, Tatemichi S, Okuhara Y

This study evaluated the effects of difelikefalin, a kappa opioid receptor (KOR) agonist, on the inflammatory response and renal dysfunction in a rat model of acute kidney injury induced by renal ischemia-reperfusion injury, comparing it with other KOR agonists.One week after right nephrectomy, r...

Yang H, Pei M, Zhai J, Zhou Z, Xing Y, Lan Q et al.

Uraemic pruritus (UP) is an increasingly significant health burden. However, current treatments are often unsatisfactory and associated with numerous adverse reactions. Recently, several large randomized controlled trials (RCTs) have confirmed that kappa opioid receptor (KOR) agonists, which targ...

McCafferty K, Collins C, Taylor I, Schaufler T, Baxter G

Background/Objectives: CKD-associated pruritus (CKD-aP) is a serious systemic comorbidity occurring in patients with CKD. Despite the burden of CKD-aP, there are limited efficacious treatments available for its management; difelikefalin is the only approved treatment based on its efficacy and saf...