Chronic Kidney Disease-associated Pruritus Research Articles

Alleviating symptoms in patients undergoing long-term hemodialysis: a focus on chronic kidney disease-associated pruritus.

Since the breakthrough of kidney replacement therapy, increases in life expectancy for patients with end-stage kidney disease have been limited. However, patients have become increasingly vocal that, although mortality and life expectancy matter to them, the quality of their life, and particularly the relief of symptoms associated with their treatment, are in many cases more important. The majority of dialysis-associated symptoms and adverse effects do not currently have any approved treatments in this patient population, with the few treatments that are available used off-label, frequently without proven efficacy, yet still potentially adding further adverse effects to patients' current symptom burden. This article will illustrate how understanding the pathophysiology of a single, particularly burdensome symptom of dialysis (chronic kidney disease-associated pruritus) resulted in the design, development and regulatory approval of a treatment for that symptom. The pathway described here can be applied to other symptoms associated with dialysis, meaning that if we cannot add years to patients' lives, we can at least add life to their remaining years.

Pruritus in Chronic Kidney Disease: An Update

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP.

Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review.

Chronic kidney disease-associated pruritus (CKD-aP) is a chronic condition that significantly reduces the quality of life of patients with end-stage renal disease. The etiology is not fully understood, but imbalance in the activity of the opioid pathways, including downregulation of the kappa-opioid receptor, may contribute to itching sensation. Difelikefalin is a selective, peripherally acting kappa-opioid receptor (KOR) agonist. Recently, difelikefalin has been approved as a first drug for the treatment of pruritus associated with chronic kidney disease (CKD) in adult hemodialysis patients. A systematic review of currently available clinical trials was performed to assess the efficacy and safety of difelikefalin in patients with uremic pruritus. A literature review was conducted in May 2022 based on the PRISMA 2020 guidelines. The analyzed clinical trials showed that difelikefalin was effective in reducing pruritus in patients as assessed by the Worst Itching Intensity Numerical Rating Scale. Improvement in quality of life assessed on the basis of the Skindex score and the 5-D itch scale was also noticed. The most commonly reported side effects were mild and included nausea, vomiting, dizziness, and diarrhea. Due to its proven efficacy and good safety profile, difelikefalin is a promising drug for the treatment of pruritus in patients with chronic kidney disease.

Nemolizumab: First Approval.

Nemolizumab is a subcutaneously administered humanized anti-interleukin-31 (IL-31) receptor A (IL-31RA) monoclonal antibody that is being developed by Chugai Pharmaceutical Co. Ltd, Maruho Co. Ltd and Galderma Pharma S.A. for the treatment of skin diseases, including atopic dermatitis (AD), AD associated pruritus (ADaP), prurigo nodularis (PN), chronic kidney disease associated pruritus (CKDaP) and systemic sclerosis (SSc). IL-31 is a neuroimmune cytokine that induces itch, inflammation, keratinocyte differentiation and fibroblast activation in chronic pruritic skin diseases. Nemolizumab (Mitchga® Syringes) was approved in Japan on 28 March 2022 for use in adults and children over the age of 13 years for the treatment of itch associated with AD (only when existing treatment is insufficiently effective). This article summarizes the milestones in the development of nemolizumab leading to this first approval.

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

Rationale & ObjectiveWe report a pooled safety analysis of intravenous difelikefalin in participants with moderate to severe chronic kidney disease–associated pruritus (CKD-aP) treated by hemodialysis in 4 phase 3 clinical studies.Study DesignKALM-1 and KALM-2 were randomized, double-blind, placebo-controlled, pivotal phase 3 studies; CLIN3101 (52 weeks) and CLIN3105 (12 weeks) were open-label studies.Setting & ParticipantsAdults with moderate to severe CKD-aP treated by hemodialysis in North America, Europe, and the Asia-Pacific region.InterventionAt least 1 intravenous placebo or difelikefalin dose of 0.5 mcg/kg for up to 64 weeks.OutcomesSafety.ResultsSafety analyses were conducted with 848 participants in the placebo-controlled cohort (424 participants each in the difelikefalin and placebo groups) and in 1,306 participants in the all-difelikefalin-exposure cohort. In the placebo-controlled cohort, the most commonly reported treatment-emergent adverse events (TEAEs), occurring in ≥2% of participants receiving difelikefalin and with a ≥1% higher incidence than placebo, were diarrhea (9.0% and 5.7%, respectively); dizziness (6.8% and 3.8%, respectively); nausea (6.6% and 4.5%, respectively); gait disturbances, including falls (6.6% and 5.4%, respectively), hyperkalemia (4.7% and 3.5%, respectively); headache (4.5% and 2.6%, respectively); somnolence (4.2% and 2.4%, respectively); and mental status changes (3.3% and 1.4%, respectively). These were mostly mild or moderate, with few leading to discontinuation. Incidence rates of TEAEs, serious TEAEs, and discontinuations because of TEAEs did not increase with long-term exposure. Three participants (0.7%) in the difelikefalin group and 5 participants (1.2%) in the placebo group died during the study.LimitationsPooled data from studies with different designs.ConclusionsIntravenous difelikefalin demonstrated an acceptable safety profile, was generally well tolerated with long-term use, and may address the unmet treatment need for patients with CKD-aP treated by hemodialysis.FundingCara Therapeutics, Inc.Trial RegistrationKALM-1 is registered as NCT03422653, KALM-2 as NCT03636269, CLIN3101 as NCT03281538, and CLIN3105 as NCT03998163.

Prevalence of pruritus associated with hemodialysis and its association with sleep quality among hemodialysis patients: a multicenter study

BackgroundCKD-associated pruritus (chronic kidney disease-associated pruritus) is one of the common symptoms in hemodialysis patients, with a major effect on sleep quality because it occurs at night. The main objective of this study is to determine the prevalence of pruritus among hemodialysis (HD) patients and its impact on sleep and investigate factors associated with pruritus and sleep quality.MethodsA cross-sectional study began in January until March of 2021 in HD centers of four different hospitals in the West Bank, Palestine. Patients with HD aged 18 years or older were included in our investigation. Pruritus and sleep problems were assessed by a 5-D itching score and the Pittsburgh Sleep Quality Index (PSQI) score.ResultsOf 280 HD patients, 250 were accepted to participate in our study. The mean age of the participants was (54.9 ± 15.08). 62.8% were male, and 42.4% of the participants were elderly (age ≥ 60yrs). Pruritus was observed in 121 (48.4%). The 5-D itching score had a median [IQR] of 5.0[5.0–15.0], and 57.2% had a score ≥ 6 points. Severe pruritus was reported in 28.1% of patients. The score was significantly associated with residency (p = 0.033) and chronic comorbidities (p = 0.026). The PSQI score has a median [IQR] of 8[5–12], and 66.4% are poor sleepers with a score of < 5. The score was significantly associated with age (p = 0.017), marital status (p = 0.022), occupational status (p = 0.007), chronic comorbidities (p > 0.001), chronic medication (p = 0.008), severity of pruritus (p = 0.003) and duration of pruritus (p = 0.003). Regression analysis showed that the 5-D itching score and the total number of comorbidities were significantly associated with the PSQI score.ConclusionsPruritus is a widespread complication among HD patients in Palestine. Pruritus also has major effects on sleep quality and is associated with poor sleep quality.

Omega-3 Fatty Acids Improve Chronic Kidney Disease-Associated Pruritus and Inflammation.

Background and Objectives: Chronic kidney disease-associated pruritus (CKD-aP) is a common symptom in hemodialysis patients. A frequent and intense itching sensation largely torments patients, impacts quality of life outcomes, and it has an independent association with mortality. The objective of this study is to investigate the effects of oral supplementation with omega-3 polyunsaturated fatty acid (omega-3 PUFA) on circulating interleukin-6 (IL-6), cardiometabolic parameters, skin moisturization, and the consequent symptoms of pruritus in hemodialysis patients. Materials and Methods: Volunteers on maintenance hemodialysis with very severe pruritus symptoms were enrolled in this prospective cohort study. Subjects were instructed to consume 1000 mg fish oil once daily for 3 months. Pruritus scoring, skin moisture, plasma IL-6, and cardiometabolic parameters were measured at baseline, and at the first, second, and third month post-supplementation with fish oil for assessment of the clinical significance. Results: A total of 27 patients who had a mean age of 67.33 ± 11.06 years and 3.98 ± 3.23 years on hemodialysis completed the study. Supplementation with omega-3 PUFA significantly decreased IL-6 levels (p < 0.001), but increased the levels of c-reactive protein (CRP) (p < 0.05). Evaluation of the cardiovascular risk showed significant (all p < 0.001) decreases in the total cholesterol (CHO), low-density lipoprotein (LDL), and triglycerides (TG) levels, and an increase in the high-density lipoprotein (HDL) level. A significant decrease in plasma creatinine (CR) was observed (p < 0.001), but the decrease was limited. Supplementation with omega-3 PUFA significantly improved (all p < 0.001) skin hydration on both the face and arms, as well as disease-related symptoms of pruritus. Conclusion: Omega-3 PUFA supplementation improved inflammation, renal function, cardiovascular parameters, dry skin conditions, and the consequent symptoms of pruritus in hemodialysis patients.

Prevalence of chronic kidney disease-associated pruritus, and association with depression among hemodialysis patients in Khyber Pakhtunkhwa

Chronic kidney disease-associated pruritus (CKD-aP), formerly known as the uremic pruritus, is commonly observed in the patients with the hemodialysis. This study aimed to determine the prevalence of the Ckd-aP and to associate it with depression in hemodialysis patients. A multicenter cross-sectional study was conducted on the patients of CKD-aP Khyber Pakhtunkhwa, from March 2021 to March 2022. This research was conducted at multiple hospitals in the Khyber Pakhtunkhwa (different hospitals such as Hayat Abad Medical Complex, Zia Medical complex, Irfan General Hospital, and others). The sample size for this research was 1000, of which 700 were confirmed patients with the CKD-aP. Research shows that the prevalence of CKD-aP is higher in males than in females. This disease creates a negative impact on mental health and causes a range of depressive disorders, among diseased persons.

MO901: Longitudinal Pruritus Assessment in Hemodialysis Patients: 1-Year Course of Symptoms and Associations With Clinical and Patient-Reported Outcomes

Abstract BACKGROUND AND AIMS The burden of chronic kidney disease-associated pruritus (CKD-aP) in hemodialysis (HD) patients, and its association with adverse clinical events and patient-reported outcomes (PROs) has been well-established. However, most studies focus on a single baseline CKD-aP assessment. In this study, we quantify the extent to which pruritus symptoms vary &amp;gt;1 year, and relationship with associated clinical and patient-reported outcomes. METHOD We included 7976 HD patients across 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4–6 (2009–18) who had 2 CKD-aP assessments 12 months (±6 months) apart, with concurrent PRO collection. CKD-aP intensity was assessed by a single question in the KDQOL-36 asking about the extent patients were bothered by itch over the past 4 weeks. We categorized patients into 4 groups—those at least moderately (versus somewhat or not at all) bothered by itchy skin in Year 1 only (Yes/No), Year 2 only (No/Yes), neither (No/No), or both (Yes/Yes) time points. Difference-in-difference analyses were used to estimate changes in laboratory values and PROs between Years 1 and 2, by within-patient changes in CKD-aP severity. Cox regression was used to estimate rates of mortality and hospitalization, with follow-up starting after the Year 2 CKD-aP assessment, across the 4 exposure groups, adjusted for confounders. RESULTS Half of the patients were at least moderately bothered by pruritus over the course of 1 year: 22% of patients were at least moderately bothered by CKD-aP at each annual assessment (Yes/Yes); 14% each were bothered at Year 1 only (Yes/No) or Year 2 only (No/Yes); 49% were not bothered at either CKD-aP assessment (No/No). These proportions were similar across DOPPS regions. Changes in laboratory values—including calcium, phosphorus, parathyroid hormone (PTH), albumin, hemoglobin, single pool Kt/V—between Years 1 and 2 varied minimally by within-patient changes in CKD-aP. Changes in some targeted PROs (depression, sleep quality, feeling faint or drained) tracked closely with changes in CKD-aP: the proportion of patients reporting &amp;gt; = 3 nights/week of restless sleep increased from 38% to 48% in the No/Yes group, decreased from 48% to 40% in the Yes/No group, and was unchanged between Years 1 and 2 in the No/No and Yes/Yes groups (Table 1). Changes in more general PROs (physical [PCS] and mental [MCS] component summary scores) were modest, and only varied by 2–3 points across the 4 CKD-aP exposure groups. The all-cause mortality HR (95% confidence interval), compared with the No/No reference group, was 1.22 (0.99–1.51) for Yes/No, 1.32 (1.07–1.63) for No/Yes and 1.31 (1.11–1.56) for Yes/Yes. Results for hospitalization and other clinical outcomes are shown in Figure 1. CONCLUSION Our findings indicate that half of chronic HD patients were at least moderately bothered by CKD-aP at some point over the course of 1 year, reflecting an unmet medical need, and that CKD-aP symptoms remained unresolved 12 months later for the majority of HD patients who were bothered by itchy skin at baseline, highlighting the chronic nature of the condition. The trend towards worse patient-reported outcomes for those affected in Year 2 but not Year 1 implicates the consequences of patients’ significant adjustment to this new, often unrelenting, symptom. Those with chronic pruritus had higher rates of hospitalization and cardiovascular events, underscoring the impact of patients with chronic pruritus on hospital systems. Moreover, those affected by pruritus at any point in the year had higher rates of mortality, further highlighting the importance of diagnosing pruritus and investigating its effect on cardiovascular events. Future research should investigate potential causes of CKD-aP symptoms more systematically and focus on how potential treatments can aide in patients’ relief.

MO131: Prevalence of Pruritus in Spanish Patients with Chronic Kidney Disease and Affectation of Quality of Life

Abstract BACKGROUND AND AIMS The prevalence of chronic kidney disease–associated pruritus (CKD-aP) found in different studies ranges from 40% to 90% in patients undergoing haemodialysis, and from 19% to 29% in non-dialysed patients. However, despite pruritus negatively affect the quality of life (QoL) and clinical outcomes as well as increase the risk of mortality, clinicians still tend to underestimate the number of patients with CKD-aP. This study was conducted to estimate the prevalence of pruritus and its impact in different dimensions of QoL in the Spanish population with CKD. METHOD A short survey was designed using seven questions included in several validated tools for pruritus assessment. The questionnaire was distributed by the Spanish Society of Nephrology to all their members in the framework of the Pruritus Week. Nephrologists visiting advanced CKD patients asked them to answer the questionnaires voluntarily. RESULTS A total of 1605 patients (haemodialysis 92%, peritoneal dialysis 5% and non-dialysis 3%) answered the questionnaire. A prevalence of CKD-aP of 50.5% was reported, 26.7% being moderate-to-severe. As shown in figure 1, the prevalence was higher in non-dialysis advanced CDK patients suggesting a benefit of dialysis in reducing itch. CKD-aP patients reported itching throughout their body and at any part of the day, but more at night. The percentage of patients with mood changes increased as the severity of itch increased, being anguish and lack of rest the parameters that were more highly affected. An increase in depression was also observed. Sexual function and desire impairment increased as severity of CKD-aP increased. Finally, CKD-aP patients reported higher sleeping disturbances than patients with no pruritus (difficulty to sleep, restless sleep and intake of sleep medication), which enhanced with the increase of pruritus severity. CONCLUSION CKD-aP is highly prevalent in patients with advanced CKD (non-dialysis and dialysis), which affects patients’ quality of life by inducing mood changes, including depression, impairing sexuality and affecting sleep.

MO677: Prevalence and Characteristics of Chronic Kidney Disease-Associated Pruritus in Home Hemodialysis Patients Compared to Dialysis Peritoneal and in-Center Hemodialysis

Abstract BACKGROUND AND AIMS Chronic kidney disease-associated pruritus (CKD-aP) is a very common symptom in dialysis patients and can significantly limit their quality of life and survival. While the prevalence of CKD-aP in peritoneal dialysis (PD) and in-center hemodialysis (HD) patients has been studied, little data are known for home HD (HHD) patients. The objective of this study was to analyse the prevalence of pruritus in HHD patients, and the factors associated with its presentation, as compared to PD and in-center HD patients. METHOD Cross-sectional, single-center study that included all patients on chronic dialysis treated at our center in November 2021. The patients were divided into three groups according to the dialysis modality (HHD, PD and in-center HD). All the patients answered a validated questionnaire on CKD-aP that evaluated the presence of itching, its intensity, frequency and location; the moment of appearance; the effect on quality of life, emotional state, cognitive function, sexual activity and quality of sleep. Likewise, it was assessed whether they had previously been diagnosed and treated for CKD-aP. The visual analogue scale (VAS) was used to define the intensity of itching as absent (VAS = 0), mild (VAS = 1–2), moderate (VAS = 3–6) or severe (VAS = 7–10). Clinical and analytical variables were compared between the groups, and the factors associated with the presence of pruritus were analysed using binary logistic regression. RESULTS Nighty-nine patients (41% women) were included, with a mean age of 64 ± 15 years and a median stay on dialysis of 57 (IQR: 17–159) months. The proportion of patients on HHD, PD and in-center HD was 20%, 41% and 39%, respectively. A total of 36% of the patients had some degree of pruritus, being mild, moderate, and severe in 8%, 13%, and 13% of the patients, respectively. The prevalence of pruritus and its intensity was similar in all the dialysis modalities (Figure 1). In the logistic regression analysis, the dialysis modality was not associated with presence of CKD-aP. CONCLUSION In our experience, the prevalence and intensity of pruritus was similar in HHD, PD and in-center HD patients. These data suggest that the type of dialysis techniques does not influence CKD-aP prevalence.

MO467: Time to Improvement of Itch Intensity in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin

Abstract BACKGROUND AND AIMS Chronic kidney disease-associated pruritus (CKD-aP) is frequently reported by patients with CKD undergoing haemodialysis (HD), impacting sleep quality, quality of life and depression. Difelikefalin is a selective kappa-opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD. In the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials, difelikefalin significantly reduced itch intensity in HD patients with CKD-aP. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch intensity [range from 0 (no itching) to 10 (worst itching imaginable)], for which a ≥ 3-point improvement has been validated as a clinically relevant reduction in itch in this patient population. The aim of this post hoc analysis was to determine the time to clinically relevant improvement in WI-NRS score in patients with CKD-aP treated with difelikefalin. METHOD The KALM-1 and KALM-2 studies enrolled maintenance HD patients with moderate-to-severe CKD-aP [mean baseline 24-h WI-NRS score &amp;gt; 4 (KALM-1) or ≥ 5 (KALM-2)]. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo 3 times/week for 12 weeks. Patients completed the WI-NRS questionnaire daily. A post hoc analysis was performed to assess the cumulative proportion of patients achieving a ≥ 3-point improvement in WI-NRS score each week. RESULTS Two-thirds of patients treated with difelikefalin who reported a response did so within 4 weeks. A further 4 weeks of treatment resulted in over 90% of difelikefalin responders reporting a clinically relevant improvement (Figure 1). Fewer patients receiving placebo reported a reduction in itch at any time during treatment (44% versus 57% of difelikefalin-treated patients) and any improvements in pruritus were reported later than for difelikefalin-treated patients. CONCLUSION A clinically relevant response to difelikefalin is likely to be reported by most patients within 4 weeks and almost all patients benefit from improvement after a further 4 weeks of treatment. Compared with patients receiving a placebo, those treated with difelikefalin are more likely to experience clinically-relevant reductions in itch, as well as an earlier improvement in pruritus.

MO424: Relationship Between Itch Intensity and Patient-Reported Disease Improvement in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin

Abstract BACKGROUND AND AIMS Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing haemodialysis (HD), leading to poor sleep quality, reduced quality of life and depression. Difelikefalin is a selective kappa opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD, which significantly reduced itch intensity in HD patients with CKD-aP in the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch-intensity [range from 0 (no itching) to 10 (worst itching imaginable)] and the Patient Global Impression of Change (PGIC) to assess the patient's overall perception of change in itch (range from ‘very much improved’ to ‘very much worse’) relative to the start of the study. The aim of this post hoc analysis was to establish how the WI-NRS score relates to the PGIC and to assess a clinically relevant change in WI-NRS. METHOD A post hoc analysis of data from KALM-1 and KALM-2 was performed. Studies enrolled maintenance HD patients with mean baseline 24-h WI-NRS score &amp;gt; 4 in KALM-1 or ≥ 5 in KALM-2. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo three times/week for 12 weeks. Patients completed the PGIC at the end of the 12-week, double-blind treatment period, as well as completing the WI-NRS daily. Cumulative distribution function (CDF) analyses were performed at Week 12. Results are reported for 50% CDF at week 12. RESULTS For the overall population, ‘very much improved’ corresponded to a 5-to-6-point WI-NRS reduction; ‘much improved’ corresponded to a 3-to-4-point WI-NRS reduction; and ‘minimally improved’ corresponded to a 1-to-2-point WI-NRS reduction (Figure 1). CONCLUSION There is a clear relationship between the PGIC and the WI-NRS, with greater reductions in itch severity corresponding to perceptions of better overall improvement in itch following treatment with difelikefalin. A 3-point reduction in WI-NRS can be considered clinically relevant, since it was perceived by patients as equivalent to their itch being ‘much improved’. This analysis further corroborates similar clinically meaningful changes in pruritus, previously reported in patients with CKD-aP, as ≥ 3-points [1, 2].

Uremic Pruritus: From Diagnosis to Treatment.

Uremic pruritus, or chronic kidney disease-associated pruritus, is common, bothersome, and sometimes debilitating in patients with chronic kidney disease or end-stage renal disease. Due to its variable clinical manifestations, the diagnosis of uremic pruritus requires exquisite evaluation. Excluding itch resulting from other dermatological causes as well as other systemic conditions is essential for a proper diagnosis. The pathophysiology of uremic pruritus remains uncertain. Hypotheses including toxin deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance are supposed. This review summarizes the way to accurately diagnose uremic pruritus and describes the latest treatment options.

Evaluation of Serum Complement Proteins and Biochemical Parameters in Patients with Chronic Kidney Disease-associated Pruritus

Chronic kidney disease-associated pruritus (CKD-aP) is a common, troubling, and in some cases a debilitating problem for patients with chronic kidney disease (CKD), end-stage renal disease (ESRD), as well as those maintained on hemodialysis (HD) or peritoneal dialysis (PD). This study aims to assess the serum complement 3 (C3), complement 4 (C4), and biochemical parameters levels in HD patients with CKD-aP.

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

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

Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis

Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5-91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0-12.0), respectively. Serum TARC level was 481.5 (278.9-603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS (r = 0.39, p = 0.006) and 5D-J score (r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS (p < 0.001) and 5D-J score (p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS (p = 0.060) and 5D-J score (p = 0.029). Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.

The Serum Level of IL-31 in Patients with Chronic Kidney Disease-Associated Pruritus: What Can We Expect?

Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch in patients undergoing maintenance hemodialysis (HD). We evaluated the serum level of IL-31 in HD patients with pruritus, in HD patients without pruritus and in healthy controls, as well as its correlation to the severity of itch. The study enrolled 175 adult subjects. The participants were divided into three groups. Group A included 64 patients on maintenance HD with CKD-aP, Group B included 62 patients on maintenance HD not reporting CKD-aP and Group C included 49 healthy controls. Pruritus severity was assessed using the Numerical Rating Scale (NRS), and the serum levels of IL-31 were measured. The results showed that the IL-31 serum level was significantly higher in the itchy group (p < 0.001) in comparison to the patients free from pruritus. Moreover, a marginal trend towards significance (r = 0.242, p = 0.058) was observed between the IL-31 serum level and itch intensity. Our study supports earlier findings on the extended role of IL-31 in the development of CKD-aP.

Pruritus-reducing effects of omega-3 fatty acids in hemodialysis patients: A cross-over randomized clinical trial.

Chronic kidney disease-associated pruritus is a common complication in patients with end-stage renal disease. In this study, we have explored the outcome of omega-3 supplementary intake for the treatment of this symptom. This double-blinded, randomized, crossover study was conducted in two dialysis centers in which 40 hemodialysis patients suffering from pruritus were randomly assigned into two groups (Group A and Group B). Patients in Group A consumed omega-3 capsules for 4 weeks and after a washout period (6 weeks), they took placebo for another 4 weeks. The same was performed in Group B but in the reverse order. Pruritus score was determined at the baseline, Week 4, 10, and 14. Serum levels of prostaglandin E2 were also recorded at the baseline and Week 4. There was a statistically significant reduction of pruritus score in patients who took the omega-3 fatty acid supplement. The mean pruritus score decreased significantly in both first (-3.41 ± 2.62, p < 0.001) and second (-1.00 ± 1.84, p= 0.04) treatment period after omega-3 treatment; but no significant mean pruritus score difference in placebo group after both intervention periods was observed. The decrease in prostaglandin E2 amount was not statistically significant in the intervention (omega-3) group compared to the placebo group (p=0.204). Our observations indicate that omega-3 fatty acids (3 grams per day) have decreasing effects on pruritus. Also, reduction in prostaglandin E2 levels in the omega-3 group did not differ from the changes in the placebo group.

POS-601 IMPROVEMENT IN SLEEP QUALITY FROM REDUCTION OF ITCH INTENSITY IN PATIENTS WITH MODERATE-TO-SEVERE PRURITUS UNDERGOING HEMODIALYSIS

Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing hemodialysis (HD). Night-time pruritus may be a particularly burdensome symptom: In CKD-aP patients this results in poor sleep quality, an important marker of worse health-related quality of life (QoL). In phase 3 trials in patients with moderate-to-severe CKD-aP, difelikefalin (a peripherally restricted kappa-opioid receptor agonist), demonstrated significant improvements in itch intensity versus placebo at week 12, and improvements in sleep quality and itch-related QoL. The aim of the study was to evaluate the impact of reduced itch intensity on sleep quality among HD patients treated with difelikefalin or placebo in the KALM-1 and KALM-2 Phase 3 clinical trials. This post-hoc analysis used pooled data for all patients. Improvement from baseline to week 12 in itch intensity was evaluated by weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score (range 0 [no itch] to 10 [worst itch imaginable]). Change in sleep quality was assessed by the 5-D Itch scale sleep disability question (1 [never affects sleep] to 5 [delays falling asleep and frequently wakes me up at night]). Spearman’s correlation analysis was performed. Patients with a clinically meaningful (≥3-point) reduction in WI-NRS score had significantly greater improvements in mean 5-D Itch sleep disability question score (−1.5 vs −0.6 for <3-point WI-NRS score reduction; p<0.0001) from baseline to week 12 (n=709) (Figure ). A moderate correlation was observed between WI-NRS and 5-D Itch sleep disability question scores at week 12 (r =0.499, 95% confidence interval 0.442, 0.552). A significant improvement was also observed at the first assessment of sleep quality (4 weeks) for patients with a ≥3-point (vs <3-point) reduction in WI-NRS score (−1.2 vs −0.4, p<0.0001, n=761). Reduction of itch intensity correlates with improvement in sleep quality in HD patients.