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Difelikefalin (Korsuva)

Peptide

Difelikefalin is a peripherally-restricted selective kappa opioid receptor (KOR) agonist peptide. FDA-approved August 2021 as first treatment for moderate-to-severe CKD-associated pruritus in hemodialysis patients. KALM trials: 51% achieved ≥3-point itch reduction vs 28% placebo. No abuse potential. Administered IV 0.5 mcg/kg post-dialysis.

Quick Answer

What it is

Difelikefalin is a peripherally-restricted selective kappa opioid receptor (KOR) agonist peptide. FDA-approved August 2021 as first treatment for moderate-to-severe CKD-associated pruritus in hemodialysis patients.

Key findings

  • Grade A: Itch Intensity Reduction (Chronic Kidney Disease-Associated Pruritus)
  • Grade A: Itch-Related Quality of Life (Chronic Kidney Disease-Associated Pruritus)
  • Grade A: Sleep Improvement (Chronic Kidney Disease-Associated Pruritus)

Safety

No specific caution or interaction language was detected in the current summary/outcome notes.

⚠️ Research Notice

This peptide information is for educational and research purposes only. Peptides may not be FDA-approved for human use and may only be legally available for research purposes. Consult qualified healthcare professionals before considering any peptide compounds.

ℹ️ Quick Facts: Difelikefalin (Korsuva)

Quick Facts: Difelikefalin (Korsuva)

  • Best Evidence:Grade A
  • Conditions Studied:1
  • Research Outcomes:7
  • Grade A Findings:3
  • Grade B Findings:2
  • Key Effect:Chronic Kidney Disease-Associated Pruritus
A3
B2
C2
D0
1 conditions · 7 outcomes

Detailed Outcomes

A
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.
large↓Improves
A
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.
large↓Improves
A
Sleep Improvement
Significant improvement in itch-related sleep disturbance. Reduced nighttime awakening due to pruritus. Benefits consistent across demographic and disease characteristic subgroups.
large↑Improves
B
Kidney Function
25 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.
moderate↑Improves
B
Safety/Tolerability
10 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.
moderate↑Improves
C
Anti-Inflammatory Activity
5 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Pain
3 human trials support this finding. Human clinical trial data available.
small↓Improves

Research Citations (42)

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.
(2026)
PMID: 41481512
Systemic Inflammatory Markers Correlate with Chronic Kidney Disease-Associated Pruritus and Response to Treatment.
(2026)
PMID: 40409676
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.
(2025)
PMID: 40411773
The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: a systematic review and network meta-analysis.
(2025)
PMID: 40567495
Difelikefalin for CKD-aP: real world evidence of efficacy and safety in Italian patients.
(2025)
PMID: 40989995
Real-world safety of difelikefalin for chronic kidney disease-associated pruritus: initial insights from a European managed access programme.
(2025)
PMID: 41133182
Real-world effectiveness and tolerability of difelikefalin over 12 months for hemodialysis-associated pruritus.
(2025)
PMID: 41436718
Nanoliposome-sericin hydrogel microneedle patches effectively alleviate inflammation and scavenge ROS for the treatment of CKD-aP.
(2025)
PMID: 40487159
Anti-inflammatory and renoprotective effects of difelikefalin, a kappa opioid receptor agonist, in a rat model of renal ischemia-reperfusion-induced acute kidney injury.
(2025)
PMID: 40596915
Long-term efficacy of difelikefalin in hemodialysis patients with pruritus: KALM-1 and KALM-2 extension studies
(2024)
PMID: 38116287