Condition
Chronic Kidney Disease-Associated Pruritus
Chronic kidney disease-associated pruritus is persistent itching in people with advanced kidney disease, thought to stem from an imbalance in the body's opioid signaling along with inflammation. The evidence is strongest for difelikefalin: in trials, 51% of people had a meaningful drop in itch intensity versus 28% on placebo, lasting up to 64 weeks. Most of that research was in people on hemodialysis, and about half did not reach that level of relief.
Sources: PMID 39712488
- Updated
- How we grade
- 42 studies cited
- Supplements studied
- 0
- Medicines and peptides
- 1
- Graded outcomes
- 3
No supplement studies yetWe haven’t found supplement studies for Chronic Kidney Disease-Associated Pruritus. The medicines and peptides studied for it are listed below.
Prescription medicines and peptides studied, for context
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Itch-Related Quality of Life Pooled analysis: 55.5% achieved ≥15-point Skindex-10 improvement vs 40.5% placebo (P<0.001). 52.1% achieved ≥5-point 5-D Itch improvement vs 42.3% placebo (P=0.01). Sustained benefits to 64 weeks. | Improves (the measure goes down) | Large effect | 23 studies | |||
Studies that measured itch-related quality of life
| ||||||
| Itch Intensity Reduction KALM-1/2 Phase 3: 51% achieved ≥3-point WI-NRS reduction vs 28% placebo (P<0.001). Mean 4.2-point decrease vs 2.5-point placebo. Effects sustained up to 64 weeks. First FDA-approved treatment for CKD-aP. | Improves (the measure goes down) | Large effect | 22 studies | |||
Studies that measured itch intensity reduction
| ||||||
| Sleep Improvement Significant improvement in itch-related sleep disturbance. Reduced nighttime awakening due to pruritus. Benefits consistent across demographic and disease characteristic subgroups. | Improves (the measure goes up) | Large effect | 14 studies | |||
Studies that measured sleep improvement
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Key findings
- Itch-Related Quality of LifeImproves (the measure goes down)
- Itch Intensity ReductionImproves (the measure goes down)
- Sleep ImprovementImproves (the measure goes up)
Studies cited
42 studies from PubMed
- The efficacy and safety of intravenous difelikefalin for the treatment of pruritus in patients undergoing hemodialysis: a systematic review and meta-analysis of randomized controlled trials.
- Systemic Inflammatory Markers Correlate with Chronic Kidney Disease-Associated Pruritus and Response to Treatment.
- Cost-utility analysis of difelikefalin for the treatment of moderate to severe Chronic Kidney Disease associated-Pruritus (CKD-aP) in adult patients receiving haemodialysis in Spain.
- The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: a systematic review and network meta-analysis.
- Difelikefalin for CKD-aP: real world evidence of efficacy and safety in Italian patients.
- Real-world safety of difelikefalin for chronic kidney disease-associated pruritus: initial insights from a European managed access programme.
- Real-world effectiveness and tolerability of difelikefalin over 12 months for hemodialysis-associated pruritus.
- Nanoliposome-sericin hydrogel microneedle patches effectively alleviate inflammation and scavenge ROS for the treatment of CKD-aP.
- Anti-inflammatory and renoprotective effects of difelikefalin, a kappa opioid receptor agonist, in a rat model of renal ischemia-reperfusion-induced acute kidney injury.
- Long-term efficacy of difelikefalin in hemodialysis patients with pruritus: KALM-1 and KALM-2 extension studies
- Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial.
- Efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus: A meta-analysis and systematic review.
- Efficacy and safety of different systemic drugs in the treatment of uremic pruritus among hemodialysis patients: a network meta-analysis based on randomized clinical trials.
- The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.
- Pathways for Diagnosing and Treating CKD-Associated Pruritus: A Narrative Review.
- Chronic kidney disease-associated pruritus and quality of life with difelikefalin treatment: a post hoc analysis of phase 3 data using the Skindex-10 questionnaire.
- Difelikefalin in the treatment of hemodialysis patients with pruritus: a systematic review and meta-analysis.
- Difelikefalin: A New κ-Opioid Receptor Agonist for the Treatment of Hemodialysis-Dependent Chronic Kidney Disease-Associated Pruritus
- Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis
- A Benefit/Risk Assessment of Intrathecal Difelikefalin in Chronic Kidney Disease-Associated Pruritus
- Ocular surface itch and pain: key differences and similarities between the two sensations.
- Cost Effectiveness of Difelikefalin Compared to Standard Care for Treating Chronic Kidney Disease Associated Pruritus (CKD-aP) in People with Kidney Failure Receiving Haemodialysis.
- Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis.
- The first real-world experience of IV difelikefalin to treat chronic kidney disease-associated pruritus in haemodialysis patients.
- A phase 2 study of oral difelikefalin in subjects with chronic kidney disease and moderate-to-severe pruritus.
- Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis.
- Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis.
- Phase 2 Trial of Difelikefalin in Notalgia Paresthetica.
- Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies
- Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program
- Difelikefalin (Korsuva) for chronic kidney disease-associated pruritus.
- Pruritus in chronic kidney disease.
- Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review.
- Difelikefalin for pruritus associated with renal disease.
- Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial.
- Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study.
- Effect of oral difelikefalin on uremic pruritus in subjects undergoing hemodialysis: a randomized, placebo-controlled, phase 2 study
- Difelikefalin: A Review in Moderate-to-Severe Pruritus in Adults Undergoing Haemodialysis
- An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease.
- A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus
- Peripheral kappa opioid receptor agonism and chronic pruritus
- The opioid crisis: a 21st century pain.