Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis

Figures & data

Figure 1. Pathophysiology of CKD-aP [2,12–18]. CKD-aP, chronic kidney disease-associated pruritus; IL, interleukin; KOR, kappa opioid receptor; MOR, mu opioid receptor.

Table 1. Overview of CKD-aP treatments.

Treatment	Target	Mechanism of action	Efficacy/safety	Approved/off-label for treatment of CKD-aP?	References
Difelikefalin	Immune dysfunction	Activation of kappa opioid receptors on peripheral sensory neurons and immune cells	Robust clinical efficacy and safety data from large well-designed phase 3 randomized, controlled trials	Approved in the U.S.A and Europe for treatment of moderate-to-severe CKD-aP in patients undergoing HD	[27,30,41–44]
Nalfurafine hydrochloride		Antagonization of mu opioid receptors	Evidence of efficacy in short-term studies and a multicenter randomized controlled trial in 373 patients on HD, but no difference to placebo in a double-blind crossover study. Post-marketing surveillance suggests nalfurafine is a safe and effective treatment for CKD-aP	Approved in Japan only for treatment of CKD-aP	[40,45–47]
Nalbuphine		Antagonization of mu and kappa opioid receptors	Evidence of efficacy and tolerability in clinical studies	Not approved for CKD-aP, off-label treatment	[47]
Topical tacrolimus		Immunosuppression	Efficacy was demonstrated in a small case series; however, a randomized-controlled double-blind trial reported no benefit. Extensive use may increase risk of dermatologic malignancies	Not approved for CKD-aP, off-label treatment	[40,48]
Doxepin		Tricyclic antidepressant with anti-H1 receptor effect	Evidence of efficacy and tolerability of low doses in small clinical studies	Not approved for CKD-aP, off-label treatment	[49,50]
Naltrexone		Antagonism of endogenous opiates	Limited evidence of efficacy and safety for treating other forms of pruritus	Not approved for CKD-aP, off-label treatment	[51–53]
Antihistamines		Inhibition of the histaminergic-itch pathway	Limited evidence of efficacy for CKD-aP. Additionally, histamines are not a major pruritogen in CKD-aP	Not approved for CKD-aP, off-label treatment	[12,33]
Phototherapy		Immunomodulation, through inhibiting T-helper 1- and 2-mediated immune responses, decreasing proinflammatory cytokines and induction of mast cell apoptosis	Limited evidence of efficacy in some small, open-label trials. However, regular UVB therapy is time-consuming for patients, of limited availability, and may present an increased risk of skin cancer, particularly in immunosuppressed patients	Not approved for CKD-aP, off-label treatment	[14,54–56]
Thalidomide	Immune dysfunction and neuropathy	Immunomodulation and neuromodulation	Evidence of efficacy in small clinical studies. Adverse risk profile for long-term use	Not approved for CKD-aP, off-label treatment	[57,58]
Gabapentoids	Neuropathy	Gabapentoids modulate the action of the GABA synthetic enzyme, glutamic acid decarboxylase, and the glutamate-synthesizing enzyme, branched-chain amino acid transaminase	Effective for reduction of itch intensity. Risk of potentially serious adverse effects, particularly at higher doses, including altered mental status, falls and fractures	Not approved for CKD-aP, off-label treatment	[40,59–61]
Ketotifen		Immunomodulation through mast cell blockade	Evidence of efficacy and safety profile in small clinical studies	Not approved for CKD-aP, off-label treatment	[62,63]
Topical analgesics (e.g. pramoxine and capsaicin)	Inflammatory response	Blocking the conduction of nerve impulses from the skin	Efficacy has been reported in several small trials. Adverse events commonly reported include burning, stinging, and erythema, and it should not be used over large areas	Not approved for CKD-aP, off-label treatment	[40,64–66]
Cannabinoids		Inhibition of inflammation	Limited evidence of efficacy in small clinical studies. Limited evidence available on adverse events from long-term use	Not approved for CKD-aP, off-label treatment	[40,67]
Serotonin antagonists, e.g. sertraline		Reduction of inflammatory cytokines	Evidence of efficacy in small clinical studies. Known safety profile in other populations. No dosage adjustment is necessary in patients with renal impairment	Not approved for CKD-aP, off-label treatment	[68–70]
Acupuncture		Parasympathetic innervation and positive functional connectivity of the putamen-posterior midcingulate cortex	Limited evidence of efficacy in some small trials	Not approved for CKD-aP, off-label treatment	[40,71]
Fatty acid supplementation		Treatment of any underlying essential fatty acid deficiency and reduction of inflammation	Limited evidence of efficacy in a small double-blind, randomized study	Not approved for CKD-aP, off-label treatment	[72,73]
Emollients	Xerosis	Reduction of xerosis	Efficacy has been reported in several small, uncontrolled trials	Not approved for CKD-aP, off-label treatment	[40,74]
Optimization of dialysis	Biochemical regulation	Removal of uremic toxins	Optimizing dialysis has historically been shown to reduce itch in several studies; however, several recent studies have not reported a link between serum phosphorous/calcium and pruritus Changing dialyzer type (e.g. to polymethyl methacrylate) has shown reductions in ‘dialysis itchiness’	Not applicable	[4,22,24,26,40,75–79]

CKD-aP, chronic kidney disease-associated pruritus; HD, hemodialysis; UVB, ultraviolet B.

Figure 2. Chemical structure of difelikefalin.

Table 2. Key clinical trial results of difelikefalin in moderate-to-severe pruritus associated with CKD in adults undergoing hemodialysis.

Study Publication	Design/Analyses	N	Treatment	Key efficacy results	Key safety results	Reference
Phase 2
NCT02858726 Fishbane 2020	Double-blind, controlled trial primary analysis	174	IV DFK (0.5, 1.0, or 1.5 μg/kg) or PBO TIW for 8 wks	1°: reduction at wk 8 from BL with DFK vs. PBO in WI-NRS score (P = 0.002) 2°: improvement Skindex-10, 5-D itch, and sleep disturbance scores with DFK vs. PBO (P ≤ 0.005)	TEAEs: 78% pts on DFK vs 42% on PBO ≥5% diarrhea, dizziness, nausea, somnolence, and fall	[86]
Phase 3
KALM-1 Fishbane 2020	Double-blind, PBO-controlled primary analysis	378	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	1°: ≥3-point reduction at wk 12 from BL in WI-NRS: 49.1% of pts on DFK vs. 27.9% on PBO (P < 0.001) 2°: improvement at wk 12 from BL in 5-D itch and Skindex-10 with DFK vs. PBO	Diarrhea, dizziness, and vomiting were more common in the DFK group than PBO group	[30]
KALM-1/2 Topf 2022	Randomized, PBO-controlled pooled efficacy and subgroup analyses	851	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	≥3-point reduction at wk 12 from BL in WI-NRS: 51.1% of pts on DFK vs. 35.2% on PBO (P < 0.001) Subgroups (age, sex, race, geographic region, BL use of anti-itch medication, medical conditions, and BL use of gabapentin or pregabalin): DFK favored vs. PBO At wk 12, complete WI-NRS response (≥80% of weekly scores equal to 0 or 1): 12.0% pts on DFK vs. 6.7% on PBO (P = 0.006) Decreases ≥15 points in Skindex-10 total score: 55.5% pts on DFK vs. 40.5% on PBO (P < 0.001); and ≥5 points in 5-D itch total score: 52.1% of pts on DFK vs. 42.3% on PBO (P = 0.012)	NA	[31]
KALM-1/2 Fishbane 2022	Randomized, PBO-controlled pooled long-term safety and 5-D itch	1306	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	NA	PBO-controlled cohort: Most common TEAEs in DFK and PBO groups, respectively: diarrhea (9.0% and 5.7%), dizziness (6.8% and 3.8%), nausea (6.6% and 4.5%), gait disturbance including falls (6.6% and 5.4%), hyperkalemia (4.7% and 3.5%), headache (4.5% and 2.6%), somnolence (4.2% and 2.4%), and mental status changes (3.3% and 1.4%) Mostly mild or moderate in severity, with few leading to study drug discontinuation Incidence rates of TEAEs, serious TEAEs, and TEAE-related study drug discontinuations did not increase with long-term exposure Incidence of death higher in the PBO than DFK group All-DFK-exposure cohort: Death rates aligned with mortality rates for pts undergoing HD in the USRDS 2020 report	[32]
KALM-1/2 Ahdoot 2021	Randomized, PBO-controlled post hoc analysis of pooled sleep quality data	850	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	Greater improvement in mean 5-D itch sleep disability question score from BL to wk 12 for pts with a ≥3-point (vs. <3-point) reduction in WI-NRS score: −1.5 vs. −0.6 (P < 0.0001, n = 709) Moderate correlation between WI-NRS and 5-D itch sleep disability question scores at wk 12 (r = 0.499, 95% CI 0.442–0.552) Greater improvement at first assessment of sleep quality (4 wks) for pts with a ≥3-point (vs. <3-point) reduction in WI-NRS score: −1.2 vs. −0.4 (P < 0.0001, n = 761)	NA	[87]
KALM-1/2 Fishbane 2021	Randomized, PBO-controlled pooled African American subgroup analysis	249	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	≥3-point improvement in WI-NRS: 48% of pts on DFK vs. 45% on PBO (OR 2.82; 95% CI 1.63–4.87; P < 0.001) ≥5-point improvement in WI-NRS: 36% of pts on DFK vs. 17% on PBO (OR 2.72; 95% CI 1.47–5.01; P = 0.001) ≥5-point improvement in 5-D itch: 55% of pts on DFK vs. 36% on PBO (OR 2.18; 95% CI 1.18–4.03; P = 0.013) ≥15-point improvement in Skindex-10: 49% of pts on DFK vs. 29% on PBO (OR 2.36; 95% CI 1.26–4.36; P = 0.006)	Most common TEAEs in DFK and PBO groups, respectively: diarrhea (10.4% and 6.2%), dizziness (10.4% and 2.7%), vomiting (7.4% and 4.4%), headache (5.2% and 0.9%), and hyperkalemia (5.2% and 2.7%) Serious AE incidence similar between groups	[88]
KALM-1/2 Fishbane 2022	Randomized, PBO-controlled pooled analysis of PGIC	800/851 with PGIC data	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	‘Very much’ or ‘much’ improved itch: 56% of pts on DFK vs. 39% on PBO (OR 1.94; 95% CI 1.45–2.60; P < 0.001)	NA	[89]
KALM-1/2 Csiky 2022	Randomized, PBO-controlled post hoc analysis of pooled WI-NRS score over time	851	IV DFK (0.5 μg/kg) or PBO TIW for 12 wks	WI-NRS response within 4 wks: ≥66% of pts on DFK vs. 44% PBO, and within 8 wks>90% DFK vs. 57% PBO	NA	[90]
3105 Weiner 2022	Open-label, multicenter, single-arm intervention trial/primary analysis	222	IV DFK (0.5 μg/kg) TIW for 12 wks	Clinically meaningful reduction in WI-NRS in 74% of pts Improvement in 5-D itch in 70% of pts Improvement in Skindex-10 in 63% of pts Sleep quality improvement (≥3-point reduction on NRS) in 66% of pts	Most common TEAEs related to study drug: somnolence (1.8%), hypoesthesia (1.4%), nausea (0.9%), and dizziness (0.9%) reported in 16 pts (7.2%) No deaths or serious TEAEs considered treatment-related	[91]
3105 Weiner 2021	Open-label, multicenter, single-arm intervention trial itch and sleep quality correlation analysis	222	IV DFK (0.5 μg/kg) TIW for 12 wks	≥3-point improvement in WI-NRS and SQQ score in 74% and 66% of pts at wk 12 Greater improvement in SQQ score from BL to wk 12 for pts with a ≥3-point (vs. <3-point) reduction in WI-NRS score (−5.22 vs. −1.53) and in 5-D itch sleep score (−1.83 vs. –‍0.78) From BL to wk 12, strong correlation between WI-NRS and SQQ scores (r = 0.78) and moderate correlation between WI-NRS and 5-D itch sleep disability scores (r = 0.48). Strong correlation between SQQ and 5-D itch sleep disability scores at wk 12 (r = 0.64)	NA	[92]
3105 Weiner 2022	Open-label, multicenter, single-arm intervention trial post hoc analysis on itch-related sleep disruption	222	IV DFK (0.5 μg/kg) TIW for 12 wks	At BL, 3.6%, 4.5%, 39.2%, and 52.7% pts reported no, mild, moderate, or severe itch-related sleep disruption, respectively, with 13.5% reporting the highest scores (9–10). 194 (87.4%) pts had sleep quality scores at wk 12, and 32.0%, 43.3%, 19.6%, and 5.2% reported no, mild, moderate, or severe itch-related sleep disruption, respectively, with no pts scoring >8	NA	[93]
KALM-1/2 and 3105 Weiner 2022	Open-label, multicenter, single-arm intervention trial post hoc analysis on CKD-aP severity	222	IV DFK (0.5 μg/kg) TIW for 12 wks	Mean improvement from BL to wk 12 was 51.7% for patients with moderate itch and 62.7% for severe itch. On average, itch severity improved to mild (WI-NRS <4) following 12 wks treatment with DFK, irrespective of baseline itch severity	NA	[94]

AE, adverse event; BL, baseline; CI, confidence interval; CKD, chronic kidney disease; CKD-aP, CKD-associated pruritus; DFK, difelikefalin; HD, hemodialysis; IV, intravenous; NA, not available; NRS, Numerical Rating Scale; OR, odds ratio; PBO, placebo; PGIC, Patient Global Impression of Change; pt, patient; SQQ, Sleep Quality Questionnaire; TEAE, treatment-emergent adverse event; TIW, three times per week; USRDS, United States Renal Data System; WI-NRS, Worst-Itch Numeric Rating Scale; wk, week.

Table 3. Overview of itch-related patient-reported outcome measures.

Measure	Description	References
Worst-Itch Intensity Numerical Rating Scale (WI-NRS)	Evaluates itch intensity over the previous 24 hours on an 11-point scale (range 0 to 10). WI-NRS has been validated in patients with CKD-aP, with a clinically meaningful change associated with a reduction of ≥3 points in patients with moderate-to-severe pruritus undergoing HD.	[17,22,95]
Skindex-10	Evaluates itch-related QoL across three domains: Disease, Mood/Emotional Distress, and Social Functioning. A ≥15-point reduction from baseline in the total Skindex-10 score represented a clinically meaningful change in a phase 2 clinical trial in adult HD patients with moderate-to-severe pruritus.	[22,86]
5-D itch	Assesses itch-related QoL and itch intensity over the previous 2 weeks, using five domains (Duration, Degree, Direction, Disability, and Distribution). A ≥5-point reduction from baseline in the total 5-D itch score represented a clinically meaningful improvement in a phase 2 clinical trial.	[39,86]
Sleep Quality Numerical Rating Scale	Evaluates itch interference with sleep over the preceding 24 hours on an 11-point scale, ranging from 0 (‘did not interfere’) to 10 (‘completely interfered’).
Kidney Disease Quality of Life Instrument (KDQOL)	Assesses health-related QoL measure for dialysis patients through a 36-item health survey	[96]
Patient Global Impression of Change (PGI-C)	Assesses patients’ overall perception of change in itch relative to the start of the study (from ‘Very much improved’ to ‘Very much worse’)	[97]

CKD-aP, chronic kidney disease-associated pruritus; HD, hemodialysis; KDQOL, Kidney Disease Quality of Life Instrument; PGI-C, Patient Global Impression of Change; QoL, quality of life; WI-NRS, Worst-Itch Numerical Rating Scale.

Figure 3. KALM trial design. *1 patient withdrew post-randomization and before first dose of placebo. HD, hemodialysis; IV, intravenous; U.S., United States; WI-NRS, Worst-Itch Numerical Rating Scale.

Figure 4. Assessment of patients with CKD-aP.

Figure 5. Treatment algorithm for management of CKD-aP [2,3,30,107–110]. CKD-aP, chronic kidney disease-associated pruritus; PTH, parathyroid hormone; SSRI, selective serotonin reuptake inhibitor; UVB, ultraviolet B.

Shirazian S, Aina O, Park Y, et al. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017;10:11–26.

 PubMed Web of Science ®Google Scholar

Electronic Medicines Compendium. Kapruvia summary of product characteristics. 2022. [cited 2021 Apr]. Available from: https://www.medicines.org.uk/emc/product/13735/smpc/print

 Google Scholar

Fishbane S, Jamal A, Munera C, et al. A phase 3 trial of difelikefalin in hemodialysis patients with pruritus. N Engl J Med. 2020;382(3):222–232. . DOI:10.1056/NEJMoa1912770

 PubMed Web of Science ®Google Scholar

Lipman ZM, Paramasivam V, Yosipovitch G, et al. Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches. Clin Kidney J. 2021;14(Supplement_3):i16–22.

 PubMedGoogle Scholar

Mathur VS, Kumar J, Crawford PW, et al. A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine er tablets for uremic pruritus. Am J Nephrol. 2017;46(6):450–458.

 PubMed Web of Science ®Google Scholar

Duque MI, Yosipovitch G, Fleischer AB Jr., et al. Lack of efficacy of tacrolimus ointment 0.1% for treatment of hemodialysis-related pruritus: a randomized, double-blind, vehicle-controlled study. J Am Acad Dermatol. 2005;52(3 Pt 1):519–521.

 PubMed Web of Science ®Google Scholar

Pour-Reza-Gholi F, Nasrollahi A, Firouzan A, et al. Low-dose doxepin for treatment of pruritus in patients on hemodialysis. Iran J Kidney Dis. 2007;1(1):34–37.

 PubMedGoogle Scholar

Smith PF, Corelli RL. Doxepin in the management of pruritus associated with allergic cutaneous reactions. Ann Pharmacother. 1997;31(5):633–635.

 PubMed Web of Science ®Google Scholar

Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015;87(4):685–691.

 PubMed Web of Science ®Google Scholar

Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142(5):1375–1390.

 PubMed Web of Science ®Google Scholar

Kuypers DR. Skin problems in chronic kidney disease. Nat Clin Pract Nephrol. 2009;5(3):157–170.

 PubMedGoogle Scholar

Sharma D, Kwatra SG. Thalidomide for the treatment of chronic refractory pruritus. J Am Acad Dermatol. 2016;74(2):363–369.

 PubMed Web of Science ®Google Scholar

Silva S, Viana P, Lugon N, et al. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron. 1994;67(3):270–273.

 PubMed Web of Science ®Google Scholar

Riccardi VM. A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching. Arch Dermatol. 1993;129(5):577–581.

 PubMedGoogle Scholar

Amirkhanlou S, Rashedi A, Taherian J, et al. Comparison of gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Pak J Med Sci. 2016;32(1):22–26.

 PubMed Web of Science ®Google Scholar

Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat. 2005;13(2):97–103.

 PubMedGoogle Scholar

Min S, Kim KW, Jung WM, et al. Acupuncture for histamine-induced itch: association with increased parasympathetic tone and connectivity of putamen-midcingulate cortex. Front Neurosci. 2019;13:215.

 PubMed Web of Science ®Google Scholar

Panahi Y, Dashti-Khavidaki S, Farnood F, et al. Therapeutic effects of omega-3 fatty acids on chronic kidney disease-associated pruritus: a literature review. Adv Pharm Bull. 2016;6(4):509–514.

 PubMedGoogle Scholar

Ghanei E, Zeinali J, Borghei M, et al. Efficacy of omega-3 fatty acids supplementation in treatment of uremic pruritus in hemodialysis patients: a double-blind randomized controlled trial. Iran Red Crescent Med J. 2012;14(9):515–522.

 PubMed Web of Science ®Google Scholar

Morton CA, Lafferty M, Hau C, et al. Pruritus and skin hydration during dialysis. Nephrol Dial Transplant. 1996;11(10):2031–2036.

 PubMed Web of Science ®Google Scholar

Rayner HC, Larkina M, Wang M, et al. International comparisons of prevalence, awareness, and treatment of pruritus in people on hemodialysis. Clin J Am Soc Nephrol. 2017;12(12):2000–2007. DOI:10.2215/CJN.03280317.

 PubMed Web of Science ®Google Scholar

Mathur VS, Lindberg J, Germain M, et al. A longitudinal study of uremic pruritus in hemodialysis patients. Clin J Am Soc Nephrol. 2010;5(8):1410–1419. DOI:10.2215/CJN.00100110

 PubMed Web of Science ®Google Scholar

Weisshaar E, Weiss M, Passlick-Deetjen J, et al. Laboratory and dialysis characteristics in hemodialysis patients suffering from chronic itch–results from a representative cross-sectional study. BMC Nephrol. 2015;16(1):184.

 PubMedGoogle Scholar

Rayner H, Baharani J, Smith S, et al. Uraemic pruritus: relief of itching by gabapentin and pregabalin. Nephron Clin Pract. 2012;122(3–4):75–79.

 PubMedGoogle Scholar

Fishbane S, Mathur V, Germain MJ, et al. Randomized controlled trial of difelikefalin for chronic pruritus in hemodialysis patients. Kidney Int Rep. 2020;5(5):600–610. DOI:10.1016/j.ekir.2020.01.006

 PubMed Web of Science ®Google Scholar

Topf J, Wooldridge T, McCafferty K, et al. 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. Kidney Medicine. 2022;4(8):100512. DOI:10.1016/j.xkme.2022.100512.

 PubMedGoogle Scholar

Fishbane S, Wen W, Munera C, et al. 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. Kidney Medicine. 2022;4(8):100513. DOI:10.1016/j.xkme.2022.100513.

 PubMedGoogle Scholar

Ahdoot R, Kalantar-Zadeh K, McCafferty K, et al. POS-601 IMPROVEMENT in SLEEP QUALITY from REDUCTION of ITCH INTENSITY in PATIENTS with MODERATE-TO-SEVERE PRURITUS UNDERGOING HEMODIALYSIS. Kidney Int Rep. 2022;7(2):S258. DOI:10.1016/j.ekir.2022.01.634

 Google Scholar

Fishbane S, Clegg DJ, Lerma EV, et al. Safety and efficacy of difelikefalin in black or African American Patients on Hemodialysis with CKD-Associated Pruritus: pooled Analysis of KALM-1 and KALM-2. Abstract PO0805; American Society of Nephrology Kidney Week; November 4, 2021; Virtual

 Google Scholar

Fishbane S, Walpen S, Schaufler T, et al. 405 effect of treatment with difelikefalin on itch severity in patients with chronic kidney disease-associated pruritus measured by the patient global impression of change. Am J Kidney Diseases. 2022;79(4):S123.

 Web of Science ®Google Scholar

Csiky B, Walpen S, Schaufler T, et al. MO467: time to Improvement of Itch Intensity in Patients with Chronic Kidney Disease-Associated Pruritus Treated with Difelikefalin. Nephrol Dialysis Transplantation. 2022;37(Supplement_3):gfac070.081.

 Google Scholar

Weiner DE, Vervloet MG, Walpen S, et al. Kidney Medicine. 2022;4(10):100542. DOI:10.1016/j.xkme.2022.100542.

 PubMedGoogle Scholar

Weiner DE, Walpen S, Schaufler T, et al. Itch Reduction with Difelikefalin Correlates with Improved Sleep Quality in Hemodialysis Patients with Pruritus. In: Abstract FR-OR26; American Society of Nephrology Kidney Week; November 5, 2021; Virtual.

 Google Scholar

Weiner D, Budden J, Woods S, et al. 406 Improvement in Itch-Related Sleep Disruption with Difelikefalin in Patients with Moderate to Severe Chronic Kidney Disease Associated Pruritus Undergoing Hemodialysis: a Post Hoc Analysis of an Open-Label, Multicenter Study. Am J Kidney Diseases. 2022;79(4):S124.

 Web of Science ®Google Scholar

Weiner DE, Vervloet MG, Menzaghi F, et al. Improvement of Itch with Difelikefalin in CKD Patients on Dialysis by Baseline Itch Severity. Abstract SA-PO286; American Society of Nephrology Kidney Week; November 5, 2022; Florida, U.S.A.

 Google Scholar

Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 2012;92(5):502–507. DOI:10.2340/00015555-1246

 PubMed Web of Science ®Google Scholar

Vernon M, Ständer S, Munera C, et al. Clinically meaningful change in itch intensity scores: an evaluation in patients with chronic kidney disease-associated pruritus. J Am Acad Dermatol. 2021;84(4):1132–1134.

 PubMed Web of Science ®Google Scholar

Elman S, Hynan LS, Gabriel V, et al. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010;162(3):587–593.

 PubMed Web of Science ®Google Scholar

Hays RD, Kallich JD, Mapes DL, et al. Development of the kidney disease quality of life (KDQOL) instrument. Qual Life Res. 1994;3(5):329–338.

 PubMed Web of Science ®Google Scholar

Scott W, McCracken LM. Patients’ impression of change following treatment for chronic pain: global, specific, a single dimension, or many? J Pain. 2015;16(6):518–526.

 PubMed Web of Science ®Google Scholar

Sukul N, Karaboyas A, Csomor PA, et al. Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients. Kidney Med. 2021;3(1):42–53.e41. DOI:10.1016/j.xkme.2020.08.011

 PubMedGoogle Scholar