Chronic Kidney Disease-associated Pruritus Research Articles

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

Abstract Background Pruritus is a common condition in chronic kidney disease, especially for patients receiving haemodialysis. Chronic kidney disease associated-pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL. Methods Data from phase 3 trials ([NCT03422653, NCT03636269 grouped], and NCT03998163) of the novel antipruritic difelikefalin (N = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-hour Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire). Results Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo (LS mean treatment difference –3.4; 95% CI –5.5, –1.3; P = 0.002) and greater improvements across Skindex-10 domains (disease, mood, and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P < 0.001) and Skindex-10 domains than those with a < 3-point reduction in WI-NRS score. Improvements in Skindex-10 total scores correlated with PGI-C. Conclusions Improvements in pruritus intensity following 12 weeks’ treatment with difelikefalin were associated with improvements in QoL. Larger improvements in Skindex-10 scores were seen in patients with a greater reduction in pruritus intensity, indicating that improvements in pruritus are associated with a range of factors, such as mood and social functioning, that affect pruritus-related QoL.

The role of blood purification therapies in the treatment of chronic kidney disease-associated pruritus: a systematic review

The role of blood purification therapies in the treatment of chronic kidney disease-associated pruritus: a systematic review

Pharmacological interventions for pruritus in adult palliative care patients.

Pharmacological interventions for pruritus in adult palliative care patients.

Efficacy and Safety of Omega-3 Fatty Acids in Ameliorating Pruritus in Adult Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.

Chronic kidney disease-associated pruritus (CKD-aP) represents a common distressing problem in patients with end-stage renal disease. This study aimed to assess the efficacy and safety of omega-3 supplementation in the treatment of CKD-aP. MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, Web of Science, ProQuest, and Scopus databases were searched systematically for articles published from inception until May 21, 2024. Outcomes were pruritus severity at the end of the study or its change from baseline (primary) and intervention-related adverse effects (secondary). Results were pooled as standardized mean difference (SMD) and risk ratio (RR) for numeric and dichotomous outcomes, respectively, along with their 95% confidence intervals (CIs). Eight studies were included. Treatment with omega-3 fatty acids showed a significantly lower severity of CKD-aP at the end of treatment (pooled SMD (95% CI) = -1.03 (-1.85, -0.22), p = 0.024) and changed from baseline (pooled SMD (95% CI) = -0.93 (-1.57, -0.28), p = 0.014). Omega-3 supplementation reduced the risk of CKD-aP (pooled RR (95% CI) = 0.68 (0.12, 3.81), p = 0.661). Omega-3 fatty acid supplementation appears to be a promising effective and safe treatment for CKD-aP. However, the included studies had several limitations that warrant further high-quality studies to elucidate its effect and investigate the causes of non-response in patients who did not improve.

Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies.

Chronic kidney disease-associated pruritus (CKD-aP) has historically been associated with elevated serum phosphate (sP). Difelikefalin is a novel antipruritic agent approved for the treatment of moderate-to-severe CKD-aP in adults undergoing hemodialysis. This post hoc analysis utilized data from Phase 3 difelikefalin studies (KALM-1, KALM-2, and open-label Study 3105) to assess the role of sP in the pathogenesis of CKD-aP, and whether difelikefalin ameliorates CKD-aP in patients with and without elevated sP. Patients with moderate-to-severe CKD-aP undergoing hemodialysis with baseline sP data were included in the analysis (KALM-1 and KALM-2, n=845; Study 3105, n=220). Assessments included correlation between 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score and sP. In KALM-1 and KALM-2, baseline characteristics in the overall population were similar between patients with sP ≤5.5 and >5.5 mg/dL; no significant correlation was observed between WI-NRS and sP at baseline or at Week 12. In patients receiving placebo, no correlation was observed between WI-NRS and sP at baseline or between their change from baseline to Week 12 (all p<0.05). Clinically meaningful (≥3-point) reductions from baseline to Week 12 in WI-NRS scores were reported by more patients receiving placebo with baseline sP ≤5.5 mg/dL than >5.5 mg/dL; least squares (LS) mean 37.2% versus 27.4% (odds ratio [95% CI], 0.63 [0.41, 0.97]; p=0.04). A greater proportion of patients treated with difelikefalin achieved a ≥3-point WI-NRS reduction from baseline to Week 12 versus placebo, and was similar between sP ≤5.5 and >5.5 mg/dL subgroups (LS means 51.1% vs 57.6% [p=0.20]). No significant relationships between sP and WI-NRS in patients receiving difelikefalin were identified in Study 3105 at any timepoint. No correlation was observed between pruritus severity and sP, or response to placebo or difelikefalin in patients with CKD-aP undergoing HD. Difelikefalin improved itch versus placebo irrespective of baseline sP.

Nomogram to Estimate the Risk of Chronic Kidney Disease-Associated Pruritus in Patients with End-Stage Renal Disease Undergoing Peritoneal Dialysis: Model Development and Validation Study

Plain Language SummaryWe conducted a study to better understand and predict the risk of CKD-associated pruritus, a common itching condition in patients with severe kidney disease undergoing peritoneal dialysis. Our research included an analysis of the risk factors associated with this condition. Using information from uremic pruritus patients, we developed a special tool that takes into account factors such as a patient’s age, certain blood markers, hemoglobin levels, residual urine volume, and renal Kt/V. This tool is designed to help doctors estimate a patient’s likelihood of developing CKD-associated pruritus. Our results show that this tool is not only accurate but also practical for use in medical settings, aiding doctors in making informed treatment decisions.

Skin barrier: new therapeutic targets for chronic kidney disease‐associated pruritus – a narrative review

AbstractThe current incidence of chronic kidney disease‐associated pruritus (CKD‐aP) in patients with end‐stage renal disease (ESRD) is approximately 70%, especially in those receiving dialysis, which negatively affects their work and private lives. The CKD‐aP pathogenesis remains unclear, but uremic toxin accumulation, histamine release, and opioid imbalance have been suggested to lead to CKD‐aP. Current therapeutic approaches, such as opioid receptor modulators, antihistamines, and ultraviolet B irradiation, are associated with some limitations and adverse effects. The skin barrier is the first defense in preventing external injury to the body. Patients with chronic kidney disease often experience itch due to the damaged skin barrier and reduced secretion of sweat and secretion from sebaceous glands. Surprisingly, skin barrier‐repairing agents repair the skin barrier and inhibit the release of inflammatory cytokines, maintain skin immunity, and ameliorate the micro‐inflammatory status of afferent nerve fibers. Here, we summarize the epidemiology, pathogenesis, and treatment status of CKD‐aP and explore the possibility of skin barrier repair in CKD‐aP treatment.

Difelikefalin and treatment of severe pruritus associated with chronic kidney disease - Real-life retrospective study in a dialysis center

Difelikefalin is to date the first and only specific treatment to be approved for the treatment of moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) in adult patients on hemodialysis. This was a retrospective, single-center, real-life study in hemodialysis patients with CKD-aP treated with difelikefalin. The primary objective was to evaluate the evolution of the intensity of pruritus during treatment with difelikefalin using the Worst Itch Intensity-Numerical Rating Scale (WI-NRS). Adult patients were included if they had been on hemodialysis for at least 3 months and were suffering from moderate to severe CKD-aP (objectified by the WI-NRS score) for which difelikefalin had been prescribed. 11 patients (7 men and 4 women; mean age, 63.8 years) with a mean (SD) weekly dialysis time of 13 h (2.4) were included. The mean hemodialysis duration was 5 (3.6) years and the mean pruritus duration was 4.3 (3.2) years. At inclusion, on-going treatments of CKD-aP were emollients in all patients and antihistamines in 9 patients. The mean WI-NRS score was 7.4 (1.1) at initiation of difelikefalin. At last assessment after a median follow-up of 9.0 months, the mean change of WI-NRS score was -5.1 (2.9) and 82% of patients had a decrease ≥ 3 points. Mild to moderate adverse reactions to difelikefalin were reported in 4 patients, all of whom recovered without sequelae. These results show that difelikefalin, prescribed according to its therapeutic indication, is effective in the treatment of CKD-aP under real-life conditions, outside the controlled conditions of a clinical trial.

Blood Purification for the Treatment of Chronic Kidney Disease-associated Pruritus

ABSTRACT Chronic kidney diseases-associated pruritus (CKD-aP) is a term that indicates the itching associated to end stage kidney disease without any apparent cause. This symptom leads to decreased quality of life and increased risk of long-term morbidities and mortality. The pathogenesis of uremic pruritus is still unknown, however, different theories have merged: uremic toxins deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance. While in the last decade, research focused prevalently on pharmaceutical treatment of CKD-aP, extracorporeal therapies have also evolved providing an alternative but efficient treatment option. In this review, we assess the role of different extracorporeal methods on the treatment of CKD-aP.

#1151 The prevalence and disease burden of CKD associated pruritus in Danish dialysis patients and current treatment practices—preliminary results

Abstract Background and Aims Chronic kidney disease associated pruritus (CKD-aP) is rarely assessed by health care providers and potentially under-reported by patients despite the potential negative impact on health-related quality of life (HRQoL). Our aim was to investigate the prevalence of CKD-aP in a large cohort of Danish dialysis patients based on validated patient-reported outcome (PRO) instruments. A secondary aim was to investigate CKD-aP awareness among renal physicians including current treatment practices. Method The study was designed as a non-interventional, cross-sectional multicentre study. Chronic dialysis patients from four different regions in Denmark were invited to participate. CKD-aP was assessed with a one-page questionnaire containing Danish versions of two validated PRO instruments. The worst itch numeric rating scale (WI-NRS) was used for itch severity within the previous 24 hours (ranging from 0-10 with CKD-aP defined as WI-NRS score &amp;gt;4 which equals moderate to severe CKD-aP). The 5-D itch scale was used as a multidimensional measure of itching and HRQoL. The five dimensions of the 5-D itch scale (degree, duration, direction, disability, and distribution) were summed together to obtain total score ranging from 5 (no pruritus) to 25 (most severe). CKD-aP awareness and treatment practices among doctors and nurses were investigated with a simple self-invented questionnaire. Results We recruited 500 chronic dialysis patients of which 87% were treated with in-center haemodialysis (HD), 10% with peritoneal dialysis (PD) and 3% with home HD (HHD). Mean age ± SD was 65 ± 14 years and 64% were males. Fig. 1 shows WI-NRS and total 5-D itch score distribution according to dialysis modality. CKD-aP prevalence (based on WI-NRS score &amp;gt;4) was 19% (all patients regardless of dialysis modality) but tended to be higher among PD patients (29%) in comparison with HD (18%) and HHD (23%) as shown in Fig. 1. Odds ratio (OR) with logistic regression for CKD-aP based on WI-NRS score as a binary dependent variable (≤4 or &amp;gt;4) and dialysis modality yielded: OR (PD vs. HD): 1.83 (0.96-3.49) and OR (HHD vs. HD): 1.35 (0.36-5.03). No pruritus (WI-NRS score = 0) was found in 61% of patients and 20% had mild pruritus (WI-NRS score ≤4). WI-NRS score correlated significantly with total 5-D itch score (Spearman's rank correlation coefficient (all patients): ρ = 0.80; P &amp;lt; .001). Median total 5-D itch score (IQR) was 5 (5-10) based on all patients regardless of dialysis modality. Itch intensity over the past 2 weeks was rated moderate to unbearable by 23% and not present in 54% of patients. Itch duration was less than 6 hours in 91% of patients and 29% of patients had no change in itching over the past 2 weeks. Overall, the impact of CKD-aP on daily activities (leisure/social, housework/errands and work/school) was minimal in most patients but sleep disability (score &amp;gt;1) was found in 18%. Sleep disability was significantly associated with higher WI-NRS score. Perceived CKD-aP prevalence (based on 28 questionnaires) was 20-40% according to most physicians (54%), 25% estimated it to be lower and 21% expected it to be higher. Topical therapy with fatty cream was the preferred treatment by most physicians followed by increased dialysis and non-sedating antihistamines. Conclusion Roughly one out of five patients on chronic dialysis treatment suffers from moderate to severe CKD-aP. HRQoL is negatively affected by CKD-aP primarily manifested as sleep disturbance. Most physicians tend to overestimate CKD-aP prevalence and prescribe fatty cream as their preferred treatment.

#2701 Prevalence of chronic kidney disease associated pruritus among hemodialysis patients in Switzerland

Abstract Background and Aims Chronic Kidney Disease Associated Pruritus (CKD-aP) is a frequent symptom in patients with end-stage renal disease. The reported prevalence differs between countries and is estimated between 20-40%; data on the prevalence of CKD-aP in Switzerland are lacking. This ongoing study aims to determine the prevalence and severity of CKD-aP among patients on hemodialysis in the French-speaking part of Switzerland and to investigate its association with demographic and clinical factors. Method Patients aged ≥18 years, on hemodialysis for ≥6 months, and free of cognitive impairment were recruited. Clinical, laboratory and dialysis prescription characteristics were collected by an independent research nurse, who also performed CKD-aP assessment using the Visual Analog Scale (VAS, numeric score 0-10) and the Verbal Rating Scale (VRS, 0 = no itch - 4 = extremely severe itch). Multiple linear regression analysis was carried-out to investigate associations of CKD-aP with demographic and clinical factors. Results Preliminary data from 401 participants (mean age 69.4 years, SD 13.6; 65% men) showed a CKD-aP prevalence of 24%. Most participants with CKD-aP (69%) reported generalized itching and 35% waking-up at night because of the itching. Mean VAS in participants with CKD-aP was 4.78 (SD 2.02) during the last 24 hours and 6.65 (SD 2.2) for the worst intensity itching during the last 24 hours. According to the VRS, most participants with CKD-aP suffered from moderate (60%) to severe itching (23%), and 72% experienced at least one severe to extremely severe episode of itching during the last 24 hours. Conclusion Despite high dialysis standards and easy access to medications, CKD-aP affected around 24% of patients on hemodialysis in the French-speaking part of Switzerland, and its intensity was moderate to severe. Results may help to increase clinicians’ awareness of CKD-aP, improve its regular screening, severity reporting and treatment.

#2153 Difelikefalin: a new solution against itching in CKD-aP patients

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and burdensome symptom affecting patients with advanced chronic kidney disease, with an estimated prevalence of 53.3%. The clinical presentation is extremely variable, from minor lesions to true scratch injuries, and significantly affects the patient's quality of life (QoL), sleep quality and mood, as well as being associated with increased mortality. At present, high-quality evidence on which to base treatment is limited. Currently proposed first-line therapeutic options include optimization of dialysis treatment, emollient agents, UVB light, antihistamines, gabapentin and pregabalin. Recently difelikefalin, a k-opioid receptor agonist, has been the first Food and Drug Administration (FDA) approved drug for moderate-severe CKD-aP treatment. The aim of our study is to demonstrate the efficacy of this drug in relieving symptoms in CKD-aP patients. Method For this preliminary retrospective observational study, 19 patients (9 females, 10 males) with CKD-aP performing dialysis at our Dialysis Center were recruited. All of them had appropriate Kt/V values and had previously been treated with first-line medications. The other main demographic and clinical characteristics of our population, such as calcium-phosphate metabolism and inflammation's indexes, can be seen in Table 1. Our population underwent the Worst Itch Numeric Rating Scale (WI-NRS) by which the presence, intensity, and impact on sleep of this symptom were investigated. They also were subjected to questions that investigate their quality of life (SF-PCS12, SF-MCS12). All patients completed those questionnaires before starting Difelikefalin treatment (t0) and after one month of treatment (t1), 15 of them were evaluated also after three months (t3) and 10 patients, those who first started therapy, reached the assessment at six months (t6). Results Statistical analysis of our preliminary study shows very encouraging data regarding the efficacy of difelikefalin on CKD-aP and sleep quality. As shown in Table 2, we recorded a significant decrease (p value &amp;lt;.001, ƞ2 0.552) in the intensity of itching, most noticeable in the first month, confirming that the effect of this drug is evident and considerable already after four weeks. Our data also demonstrate a significant and lasting positive effect of difelikefalin on sleep quality (p value 0.006, ƞ2 0.592), as shown in Table 3. We found no significant data on the improvement in the QoL of the patients in the study, probably due to the difficulty in standardising this complex feature and due to the limited size of the statistical sample. Furthermore, it should be considered that 3 of the patients enrolled in the study had to discontinue the medication due to the onset of side effects such as diarrhea and headache. Conclusion The most influential limitation of this retrospective observational study is the small number of recruited patients, in addition to the fact that not all of them reached a 6-months treatment evaluation. Our aim is to complete the study by enrolling a larger number of patients from our Dialysis Centre and to monitor the effect of difelikefalin during a longer treatment period, in order to achieve a more accurate analysis and significative results applicable on a larger scale. As far as we can currently evaluate, this drug is significantly effective in reducing CKD-aP and thus in improving the quality of sleep.

#802 CENSUS-EU: a cross-sectional, study to assess the prevalence and burden of chronic kidney disease-associated pruritus in Europe

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common condition that can negatively affect patients’ health-related quality of life (HRQoL). Despite this, there has been a lack of clarity on its prevalence and impact, leading to increasing interest in and need for an accurate overview of its epidemiology. Here we present the interim analyses of the real-world study CENSUS-EU to estimate the prevalence of CKD-aP and its impact on patients’ HRQoL. Method CENSUS-EU is a retrospective, cross-sectional, multicentre study across seven countries in Europe. Eligible patients (aged ≥18 years and on dialysis for ≥3 months) consenting to participate were asked to complete five patient-reported outcome questionnaires, one on CKD-aP severity (the Worst Itching Intensity Numerical Rating Scale) and four on HRQoL, including the 5-D itch scale and the integrated palliative care outcome scale symptom list for end-stage renal disease (IPOS-Renal). Patients also completed a survey on the communication and management of their pruritus, including current anti-pruritic medication use. In addition, the medical records of patients were assessed to gather retrospective information on clinical dialysis characteristics, treatment patterns and healthcare resource utilisation. In this presentation of the interim data, we report the prevalence of pruritus and the distribution of severity subgroups, how pruritus severity affects the disability score from the 5-D itch (impact on sleep, leisure, errands, and work/school), and the sleep and depression scores from the IPOS-Renal questionnaire. Results The interim analysis included 1,482 patients, of which 59.9% were ≥65 years of age and 61.2% were male. Patient characteristics were balanced across severity subgroups. Overall prevalence of CKD-aP was 52.6% (95% confidence interval 50.02, 55.10); 21.5% of patients experienced mild pruritus, 17.5% moderate pruritus, and 13.5% severe pruritus (Fig. 1). As pruritus severity increased from no pruritus to severe pruritus, patients reported greater difficulty sleeping, as shown by increasing scores for question 2 of the IPOS-Renal questionnaire (Fig. 2A). Patients with more severe pruritus also reported feeling depressed more often than those with less severe or no pruritus (Fig. 2B). There were also increasing scores for the 5-D itch disability subscale (Fig. 2C). Patients with moderate or severe pruritus were also hospitalised more often than patients with mild or no pruritus (mean 1.7 and 1.9 hospitalisations per year, respectively). Overall, 17.9% of patients were receiving at least one ongoing anti-pruritic treatment, and the proportion of patients using at least one anti-pruritic treatment became greater with increasing itch intensity. Despite the impact of pruritus on HRQoL, 40.6% of patients with severe pruritus who had ever suffered from itch while on dialysis were not receiving anti-itch treatment. Conclusion The interim results of this cross-sectional study suggest that approximately 50% of patients on haemodialysis experience CKD-aP. The data reveal that as pruritus severity increases, the effect on sleep and depression scores becomes greater, potentially impacting more deeply on patients’ HRQoL.

#1419 A single, easy-to-use question to assess pruritus intensity in daily dialysis practice

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) has been shown to negatively impact certain clinical outcomes and quality of life (QoL) in patients with kidney failure. However, regular screening for CKD-aP is not yet routine dialysis practice and no consensus on the preferred instrument exists. To facilitate implementation of regular screening for CKD-aP we assessed the performance of two different instruments validated in patients with CKD-aP. Method The Worst Itching Intensity Numerical Rating Scale (WI-NRS) asks patients to indicate the worst itch intensity in the past 24 hours (range 0 [no itch] to 10 [worst itch imaginable]). The 5-D Itch scale assesses itch-related QoL (range 5-25 where higher values indicate worse QoL) and includes one question on itch intensity over the past 2 weeks (5-D ‘degree’ domain, range 1 [not present] to 5 [unbearable]). Both instruments were included in two phase-3 clinical trials, KALM-1 and KALM-2, that established the favourable benefit-risk profile of difelikefalin over placebo in patients on haemodialysis with moderate to severe CKD-aP. WI-NRS was collected daily during the trial and 5-D Itch at the first dialysis visit in weeks 5, 9, 11 and 13. We assessed the correlations between both the 5-D total score and degree domain and a) the single WI-NRS measurement collected on the same day and b) the average of daily WI-NRS scores collected over the previous 2 weeks in all patients independent of treatment exposure. Results The two instruments demonstrated moderate to strong correlations (range 0.5635-0.7039, p &amp;lt; 0.0001) independent of whether the total 5-D Itch score or the 5-D itch degree question were compared with a single, same-day WI-NRS measurement or with the mean WI-NRS scores over the 2-week recall period of the 5-D Itch (Table). In addition, correlations remained consistent over time, supporting the reliability of the findings. Conclusion Using the WI-NRS to ask patients about their worst itch in the past 24 hours is a simple and swift approach for reliably identifying those with bothersome pruritus that also affects their itch-related QoL.

Effects of an ice roller on chronic kidney disease-associated pruritus in patients receiving haemodialysis.

Chronic kidney disease-associated pruritus is a distressing symptom and has a far-reaching impact on patients' sleep and quality of life for most patients receiving haemodialysis. Traditional therapies have limited effectiveness. This study aimed to invent a self-operated ice roller and evaluate its efficacy in relieving pruritus, sleep quality, and quality of life. This study was experimental with a two-arm parallel group design. A convenient sampling method was used to recruit 60 patients receiving haemodialysis who reported pruritus (5D-Itch Scale score >5) lasting over 4 weeks in Taiwan. The participants were randomly assigned to one of two groups: the intervention group used an ice roller for 7 days, while the control group received no anti-pruritus treatment. This study was experimental with a two-arm parallel group design. The measurement instruments included the 5D-Itch Scale, Pittsburgh Sleep Quality Index and WHOQOL-BREF-Taiwan Version. The analysis of covariance, chi-square, Independent t tests,and partial Eta2 (η2 p) were used to analyse the data. The participants' mean age was 62.77 years. Application of the ice roller significantly decreased overall pruritus (p < .05; η2 p = .09) and distribution of pruritus-associated bodily parts (p = .03; η2 p = .08). There were no statistically significant differences in sleep quality and related indicators between the experimental and control groups at the study endpoint. Regarding quality of life, only the social relationship domain significantly differed between the two groups (p = .02; η2 p = .08). The ice roller can decrease pruritus and its distribution in patients receiving haemodialysis, serving as an adjunct therapy alongside conventional anti-pruritus treatments.

Diagnosis and management of pruritus associated with chronic kidney disease in hemodialyzed patients

Chronic kidney disease-associated pruritus (CKD-aP) is a disabling symptom which is frequent and often underestimated. Pa-MRC has a negative impact on quality of life, and is frequently accompanied by sleep disorders and depression. The approval of difelikefalin – a kappa opioid receptor agonist – in this indication requires updated recommendations. As a first step, secondary causes of pruritus without skin lesions must be ruled out, and general measures taken (emollients, psychological support, optimization of dialysis, normalization of serum calcium, phosphate and PTH in the range proposed by the KGIDO guidelines, treatment of iron deficiency). A therapeutic test with a non-sedating oral antihistamine may be proposed. If this test is negative, Pa-MRC must be strongly suspected, and its intensity (WI-NRS scale) and impact on quality of life assessed. In the case of mild Pa-MRC (WI-NRS ≤ 3), only general measures are implemented. If Pa-MRC is moderate to severe (WI-NRS ≥ 4), specific treatment with difelikefaline can be initiated for 6 months in addition to general measures. At 3 months, if the response is complete (WI-NRS score ≤ 1) or partial (decline ≥ 3 points), treatment is continued. At 6 months, if the response is complete, treatment may be discontinued with the patient’s agreement; treatment is maintained if the response is partial. At 3 or 6 months, if response is insufficient (decline < 3 points) and/or in the event of intolerance, treatment is discontinued and an alternative treatment (e.g., gabapentinoids, UVB) may be considered after dermatological consultation.

Effectiveness of Narrowband Ultraviolet Light in Chronic Kidney Disease-Associated Pruritus.

Chronic kidney disease-associated pruritus (CKDaP) is a prevalent and challenging symptom in individuals suffering from advanced chronic kidney disease (CKD). Its underlying mechanism remains inadequately understood, leading to a limited array of unsatisfactory therapeutic interventions. Despite various attempts, identifying the most effective treatment remains inconclusive. Nevertheless, there is a growing interest in employing ultraviolet phototherapy, particularly for non-responsive patients, although its efficacy is not definitively established. To investigate the potential benefits of narrowband ultraviolet B (NB-UVB) phototherapy on individuals experiencing CKDaP, we report our experience with NB-UVB light in management of CKDaP in dialysis patients. The study group consisted of patients with end-stage chronic kidney disease who underwent hemodialysis. These patients received dermatological consultations and follow-ups for itching. They were all unresponsive to the conventional treatment (emollients and antihistamines). Screening laboratory examinations, including complete blood count, liver function test, thyroid function, electrolytes, and others, were also arranged to exclude systemic etiologies. The main potential pruritogens were dosed: calcium, phosphate, and parathyroid hormone. Itch intensity was evaluated with a numericalrating scale(0-10), based on the worst level ofitchingin the past two weeks.They had sessions of NB-UVB light (311 nm, TL01) twice per week. After UVB exposure, patients were advised to use topical emollients. A questionnaire was employed to document the extent, intensity, frequency, and sleep disruption experienced to evaluate the efficiency of the treatment, using a scale from 0 to 10. Results: In a group of 38 patients, the average age of the patients was 56 years (16-80); 63.2% were female and 36.8% were male. Median duration of pruritus was 4.7 years, and that of dialysis was 8.4 years. Pruritus was intermittent and diffuse in most cases, localized to the arteriovenous fistula site in two cases, and exacerbated by heat in all cases. Itch intensity was evaluated with a numerical rating scale (0-10) based on the worst level of itching in the past two weeks and showed a moderate average score (5/10). Xerosis was found in 63%, and scratch lesions such as excoriation in 34%. NB-UVB phototherapy was used twice per week on nonconsecutive days, with protection of the genital area and also the eyes using UVB-blocking goggles. The initial dose was 0.4 J/cm2and further doses were introduced according to the erythema response until a maximum of 2 J/cm2. No sunburn, hyperpigmentation, or blistering was noted. Emollients were maintained in patients with xerosis. Average number of sessions was 13 (6-24)and reduction of itch intensity was observed starting from the sixth session. Total improvement was obtained at the end of treatment duration except for three patients who required additional sessions. One patient had recurrence one year later. Conclusion: In conclusion, phototherapy represents a significant advancement in the treatment options for CKD-associated pruritus. Its positive impact on reducing itching and improving the quality of life for many patients is undeniable. However, to fully unlock its potential, ongoing research is needed to optimize dosing, understand relapse mechanisms, and identify the patients who will benefit most from this therapy.

Practical Use of Patient-Reported Outcome Measures in Chronic Kidney Disease-Associated Pruritus

Regulatory and clinical stakeholders are increasingly advocating for the use of patient-reported outcome (PRO) measures; however, the use of PROs is still not widespread. Patient reports are often the best ways to diagnose and monitor the effect of treatment on symptoms when the symptoms are subjective, as with pruritus. While many PRO tools are available to assess the severity of pruritus and its impact on quality of life (e.g., sleep), these are not used in a consistent manner and their results may not translate into clinical action. In this article, we present an introduction to PROs and their use in the assessment of chronic kidney disease-associated pruritus, as well as a practical guide to some of the PRO tools currently available, to empower all members of the nephrology patient care team to use these tools appropriately for the benefit of the patient.

Effectiveness of omega-3 fatty acid supplementation for pruritus in patients undergoing hemodialysis.

Patients undergoing hemodialysis (HD) frequently experience the chronic kidney disease-associated pruritus (CKD-aP). The aim of this study was to investigate the effectiveness of omega-3 supplementation in the management of CKD-aP in patients undergoing hemodialysis. In this triple blind, randomized clinical trial, the effect of the omega-3 supplement on uremic CKD-aP was assessed in 112 chronic hemodialysis patients at Caspian Hemodialysis Center in Rasht, Iran. Patients were randomly divided into the intervention group receiving omega-3 supplements (3 g/day) and the control group receiving placebo containing MCT oil for 2 months. Omega-3 supplementation had no effect on CKD-aP. The results did not change after adjusting for age and sex, additional adjustments for weight, height, physical activity, smoking, and alcohol use, additional adjustments for underlying diseases and weight, height, physical activity, smoking, and drinking alcohol, and further adjustments for underlying diseases and biochemical indices. Omega-3 supplementation for 2 months had no effect on CKD-aP in patients with CKD. Further studies with longer duration are warranted. https://www.irct.ir/trial/66638, IRCT20151226025699N6.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP).

Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data. Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS). Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost. This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.