Korsuva IV (difelikefalin IV) / Maruishi Pharma, Chong Kun Dang, Kissei, CSL Behring - LARVOL DELTA

Real-world effectiveness and safety of difelikefalin for chronic kidney disease-associated pruritus: a systematic review. (PubMed, Ren Fail) - "However, included studies are heterogeneous and at high risk of bias. Future research should investigate difelikefalin in peritoneal dialysis and earlier-stage CKD cohorts, alongside health economic evaluations and implementation studies."

Journal • Real-world evidence • Review • Addiction (Opioid and Alcohol) • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Difelikefalin Treatment in Chronic Kidney Disease-Associated Pruritus: Modelling Infection-Related Hospitalisation Cost Offsets Using Trial and Real-World Data Across Seven European Countries. (PubMed, Adv Ther) - "Modelling difelikefalin's clinical benefits on real-world IRH-associated costs projected substantial potential cost offsets nationally, indicating how CKD-aP management may offer economic value in patients undergoing haemodialysis."

Journal • Real-world evidence • Chronic Kidney Disease • Dermatology • Infectious Disease • Nephrology • Pruritus • Renal Disease

The neuroimmune architecture of uremic pruritus: mechanisms and therapeutic targeting. (PubMed, J Nephrol) - "Framed this way, it may help contextualize the observed benefits of therapies such as gabapentinoids and difelikefalin, clarify the limited performance of traditional antihistamine-based strategies, and support a more structured approach to bedside phenotyping and future enrichment-based trials. Prospective validation remains necessary before mechanism-guided therapeutic matching can be recommended as routine clinical practice."

Journal • Dermatology • Inflammation • Nephrology • Pruritus • Renal Disease • B3GAT1

Pharmacology of pruritus (pathophysiology, therapeutic targets). (PubMed, Therapie) - "Recent breakthroughs include biologics targeting TH2 pathways (dupilumab, nemolizumab), JAK inhibitors, κ-opioid receptor agonists (difelikefalin), and IBAT inhibitors (for cholestatic pruritus). Novel targets under investigation include MRGPRs, PARs, KIT receptors, OX-40, and sodium channels."

Journal • Addiction (Opioid and Alcohol) • Anesthesia • Dermatology • Immunology • Pain • Pruritus • Urticaria • IL13 • IL4

Difelikefalin-associated adverse drug event signals: a real-world pharmacovigilance study from the FAERS database. (PubMed, Nephrol Dial Transplant) - "This pharmacovigilance study identifies potential neuropsychiatric safety signals associated with difelikefalin, with a particularly elevated risk in elderly patients. These findings identify elderly hemodialysis patients as the high-risk group for difelikefalin-related ADEs, and suggest the need for targeted clinical monitoring strategies for this population; all signals require prospective cohort studies to validate potential causal relationships."

Adverse events • Journal • Real-world evidence • Chronic Kidney Disease • CNS Disorders • Dermatology • Mental Retardation • Musculoskeletal Diseases • Nephrology • Orthopedics • Pruritus • Psychiatry • Renal Disease

Real-World Effectiveness and Safety of Difelikefalin for Chronic Kidney Disease-Associated Pruritus: A Systematic Review (ERA 2026) - "Prospective studies in peritoneal dialysis and earlier-stage CKD cohorts are needed, alongside health- economic evaluations and implementation studies to understand barriers to uptake, long-term adherence, and real-world impact on symptom burden and patient-reported outcomes. Image"

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Review • Addiction (Opioid and Alcohol) • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

The optimal screening, diagnosis, and treatment of chronic kidney disease-associated pruritus (CKD-aP) in individuals on haemodialysis: a Delphi study (ERA 2026) - "Difelikefalin is currently the only licensed treatment for CKD-aP; however, a lack of clear screening pathways, consistent diagnostic criteria, and management guidance continues to hinder optimal care...Implementation of the recommendations is hoped to facilitate more consistent, patient-centred care by supporting earlier recognition of symptoms, standardised assessment using patient-reported, itch-specific tools, individualised treatment, and multidisciplinary management, ultimately improving outcomes for individuals with CKD-aP. Image Figure 1: Consensus recommendations"

Clinical • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Real‑world evaluation of difelikefalin and itch burden in haemodialysis patients: a regional centre experience (ERA 2026) - "CKD‑aP remained common and undertreated. Based on data evaluated, a systematic assessment tool, SOP, patient leaflet, and clinical pathway have been developed network- wide to support clinicians."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Pruritus • Renal Disease

Real-World Use of Difelikefalin (Kapruvia) for CKD-Associated Pruritus in Haemodialysis (ERA 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Chronic Kidney Disease • Dermatology • Pruritus

Development of a SMEDDS for oral delivery of hydrophilic peptide difelikefalin acetate: Preparation, characterization, and PK/PD evaluation. (PubMed, J Pharm Sci) - "In vitro release results showed that the DF solution was almost completely released at 8 h in pH 6.8 medium, while the DF self-microemulsion only achieved approximately 20% release at 24 h. Enzymatic degradation experiments demonstrated that trypsin, elastase, and α-chymotrypsin could not effectively degrade DF. The rat pharmacokinetic study showed that, relative to intravenous administration, the oral bioavailability of the DF solution was 0.656%, whereas that of DF self-microemulsifying drug delivery systems (SMEDDS) was 2.04%, representing a 3-fold increase. In the mouse pharmacodynamic test, the scratching episodes inhibition of orally administered DF SMEDDS at a dose of 5 mg/kg was comparable to that of DF injection at 0.3 mg/kg."

Journal • PK/PD data • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease • CTRC • ELANE

Difelikefalin in gabapentinoid-refractory CKD-associated pruritus: real-world experience from Australia. (PubMed, J Nephrol) - No abstract available

Journal • Real-world evidence • Dermatology • Pruritus

Innovative Microneedle Patches for Psoriasis Treatment: A Dual Approach With Methotrexate-Zinc and Difelikefalin for Enhanced Therapeutic Outcomes. (PubMed, Small) - "Transcriptomic analysis further revealed that DFK suppressed Schwann cell EMT pathways. Together, this dual-functional microneedle platform provides a synergistic therapeutic strategy that combines rapid itch relief with long-term anti-psoriatic and antibacterial effects, representing a promising approach for improving psoriasis management."

Journal • Dermatology • Immunology • Infectious Disease • Inflammation • Pruritus • Psoriasis

Real-world effectiveness of difelikefalin for CKD-aP in UK haemodialysis: a single-centre experience. (PubMed, Clin Kidney J) - No abstract available

Journal • Real-world evidence

Refractory Chronic Kidney Disease-Associated Pruritus: Old Remedies and Novel Agents. (PubMed, Kidney Med) - "The first case involves a patient receiving hemodialysis who achieved significant symptom relief with a subcutaneous lignocaine infusion, delivered using a syringe driver over 2 weeks followed by oral mexiletine. The second case concerns a kidney failure patient managed on the conservative kidney management pathway, who experienced marked improvement following weekly intravenous difelikefalin despite not receiving chronic hemodialysis. These cases underscore the challenges faced by patients and clinicians in managing severe CKDaP and its profound impact on quality of life and emotional distress. Furthermore, these cases highlight the variability in individual treatment responses and the therapeutic potential of repurposed medicines and emphasize the need for further research in this area."

Journal • Chronic Kidney Disease • CNS Disorders • Dermatology • Nephrology • Pruritus • Renal Disease • Sleep Disorder

A kappa opioid receptor agonist, difelikefalin, improves acute kidney injury in experimental sepsis models. (PubMed, PLoS One) - "LPS administration tended to increase cytokine expression in isolated renal kappa receptor-positive cells, and difelikefalin suppressed these changes. Overall, difelikefalin demonstrated renal protective effects against AKI in murine endotoxemia and polymicrobial sepsis models and improved survival in post-ischemia/reperfusion endotoxemia."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Infectious Disease • Nephrology • Pain • Pruritus • Renal Disease • Reperfusion Injury • Septic Shock

Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling. (PubMed, Nat Commun) - "Difelikefalin is an FDA-approved κ-opioid receptor (KOR) peptide agonist used to treat chronic pruritus...Structural, molecular dynamics simulations and 2D 13C-Met NMR analyses further reveal beta01 stabilizes a unique KOR conformation with an expanded intracellular cavity that disfavors β-arrestin binding. This work establishes a rational structure-based framework for designing safer and more effective GPCR-targeted therapeutics."

Journal • Anesthesia • Dermatology • Mood Disorders • Pruritus • Psychiatry

Difelikefalin for Itching in Hemodialysis Patients With Chronic Kidney Disease (clinicaltrials.gov) - P=N/A | N=106 | Not yet recruiting | Sponsor: Chittagong Medical College

New trial • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Difelikefalin in Chinese patients with chronic kidney disease-associated pruritus. (PubMed, Clin Kidney J) - "Adverse events were mostly mild or moderate in severity and generally consistent with the known safety profile of difelikefalin. Difelikefalin effectively reduced pruritus intensity and improved quality of life in Chinese patients with CKD-aP receiving haemodialysis, supporting its use in this population."

Journal • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

DIFELIKEFALIN USE IN HAEMODIALYSIS RECIPIENTS WITH GABAPENTINOID-REFRACTORY CHRONIC KIDNEY DISEASE ASSOCIATED PRURITUS (ISN-WCN 2026) - "2 patients experienced relapses in itch (WI-NRS increase of >3-points after initial >3-point reduction) and were diagnosed with conditions unrelated to CKDaP, and itch resolved after appropriate alternate treatments.Download: Download high-res image (232KB)Download: Download full-size imageFigure 1. Worse-Itch Numerical Rating Scale (WI-NRS) after initiation of DifelikefalinConclusion Difelikefalin is an effective and well-tolerated treatment for CKDaP in patients who have failed treatment with gabapentin or pregabalin, therefore providing a useful therapeutic option for refractory cases of CKDaP.I have potential conflict of interest to disclose.Dr Li has received honoraria from CSL Seqirus.I did not use generative AI and AI-assisted technologies in the writing process."

Alzheimer's Disease • Chronic Kidney Disease • Cognitive Disorders • Dermatology • Movement Disorders • Nephrology • Pruritus • Renal Disease • Restless Legs Syndrome • Sleep Disorder

EFFECTS OF DIFELIKEFALIN ON INFLAMMATORY RESPONSES AND RENAL DYSFUNCTION IN A RAT MODEL OF RENAL ISCHEMIA- REPERFUSION-INDUCED ACUTE KIDNEY INJURY (ISN-WCN 2026) - "Difelikefalin suppressed all elevated cytokines to the same levels as those in the sham group, U-50488H showed moderate efficacy by suppressing 6 of 13 cytokines, and nalfurafine hydrochloride exhibited a poor inhibitory effect, affecting only 1 of 13 cytokines.Conclusion These findings indicate that difelikefalin has anti-inflammatory and renoprotective effects in a rat acute kidney injury model, and that there is variable anti-inflammatory efficacy among KOR agonists.The content of this abstract was submitted to the 69th Annual Meeting of the Japanese Society for Dialysis Therapy, held in June 2024 in Yokohama, and it was published in BMC Nephrology (Takeuchi H, et al. 2025 Jul 1; 26(1): 307).I have potential conflict of interest to disclose.Employee of Kissei Pharmaceutical Co., Ltd.I did not use generative AI and AI-assisted technologies in the writing process."

Preclinical • Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • CSF2 • IFNG • IL10 • IL12A • IL13 • IL17A • IL18 • IL1B • IL2 • IL4 • IL5 • IL6 • IL7 • TNFA

EFFICACY OF SUBCUTANEOUS LIDOCAINE INFUSION FOR CKD-ASSOCIATED PRURITUS (CKD-AP) (ISN-WCN 2026) - "Furthermore, CKM patients have difficulty accessing intravenous difelikefalin, which is only approved for haemodialysis patients...Other skin conditions were excluded following dermatology review and multiple therapies had been trialled, including regular aqueous emollients, topical capsaicin, pregabalin (up to doses of 150mg BD), methylprednisone 0.1% ointment, sertraline, evening primrose oil and doxepin...No side-effects were observed. The response was sustained for 6 weeks, after which the patient deteriorated from underlying kidney failure and end of life care was provided.Conclusion Subcutaneous lidocaine infusion may be an effective and safe alternative treatment option for cases of refractory CKD-aP.I have potential conflict of interest to disclose.Dr Kelly Li receives honoraria from CSL SeqirusI did not use generative AI and AI-assisted technologies in the writing process."

Clinical • Alzheimer's Disease • Chronic Kidney Disease • CNS Disorders • Dementia • Depression • Dermatology • Diabetic Nephropathy • Insomnia • Nephrology • Pruritus • Sleep Disorder

Real-world insights into nurse-led management of CKD-associated pruritus in the UK: Results from an online survey (UKKW 2026) - "Treatments vary, with creams and antihistamines being widely used for mild CKD-aP, whilst advanced therapies (e.g., gabapentin, phototherapy) are less commonly applied, despite a specific therapy option, such as difelikefalin being available for moderate/severe CKD-aP. Nurses demonstrated strong awareness of CKD-aP, with over 95% rating screening as important. Most recognised the condition’s impact on health-related quality of life, particularly itch, sleep disturbance, work or school, and emotional wellbeing. However, routine screening is inconsistent: informal conversations predominate, and 99/103 nurses reported not using formal scales consistently, despite most finding them helpful."

Clinical • Real-world • Real-world evidence • Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Nephrology • Pruritus • Renal Disease • Sleep Disorder

Association of pruritus with comorbidities and survival in chronic kidney disease: a narrative review of the pre-difelikefalin era literature. (PubMed, Ren Fail) - "Pruritus appears to be associated with increased mortality, cardiovascular events, depressive symptoms, and healthcare costs in CKD patients. Early detection and treatment, particularly with new drugs like DFK, may improve patients' quality of life and reduce CKD-aP related."

Journal • Review • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Dermatology • Diabetes • Metabolic Disorders • Nephrology • Pruritus • Renal Disease • Sleep Disorder

Uremic Pruritus in Hemodialysis: Mechanisms, Burden, and Emerging Therapies. (PubMed, J Clin Med) - "Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies."

Journal • Review • Dermatology • Nephrology • Pediatrics • Pruritus • Renal Disease

EXPLORING KAPPA OPIOID RECEPTOR MUTATIONS IN IBD: FROM MOLECULAR PHARMACOLOGY TO DRUG DISCOVERY (CCCongress 2026) - "A focused ligand panel will include FDA-approved therapeutics (e.g. difelikefalin, anrikefon, nalfurafine), experimental drug candidates (e.g., sialorphin), and in-house designed peptides (e.g. helianorphin-19, DNCP-β-NalA). Nat Commun. 2023 Dec 6;14(1):8064."

Addiction (Opioid and Alcohol) • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease