RARE DISEASE
Uremic pruritus
Uremic pruritus
Uremic pruritus
Drug discovery
1
drug
With orphan designation
Overview
Uremic pruritus (UP), a chronic itch affecting 15-70% of chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients, arises from immune dysregulation, peripheral neuropathy, and opioid system imbalance [1][5][7]. It manifests as generalized or localized itching without primary skin lesions, often worsening at night [6][12]. Diagnosis requires exclusion of other pruritic conditions [6][12]. Management combines optimized dialysis efficiency [1][6], topical therapies, gabapentinoids [3][5], and newer κ-opioid agonists [3][5], though treatment response remains variable [9].
Burden
Reduces quality of life through sleep disruption (53% of patients) [2][5], depression [2][6], and social withdrawal [1]
Independent mortality risk factor (17-22% increased risk) [1][6][12], linked to cardiovascular events and infections [1][15]
Underreported by 17% of patients, leading to undertreatment [1][2]
Categories: rare skin diseases
Research Papers
541 drug discovery papers about Uremic pruritus, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
541 drug discovery papers about Uremic pruritus, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-18 | Literature Review: How do Omega-3 Fatty Acids Impact Uremic Pruritus in Hemodialysis Patients?
Chronic Kidney Disease-associated Pruritus (CKD-aP) is a debilitating yet often overlooked symptom. Epidemiological studies have shown that up to 40% of patients with chronic kidney disease experience moderate-to-severe pruritus. This condition is also common among patients undergoing hemodialysis. Multiple etiological factors contribute to CKD-aP, including hormonal alterations, neuropathy, increased μ- and κ-opioid receptor activity, and chronic systemic inflammation. Patients with chronic kidney disease are known to experience essential fatty acid deficiency and may therefore benefit from omega-3 fatty acid supplementation, which may help reduce inflammation and improve fatty acid balance. This review was conducted by examining prospective clinical trials investigating the effects of omega-3 fatty acids on CKD-aP that were published in English. A literature search was performed using keywords related to chronic kidney disease, uremic pruritus, dermatology, and omega-3 fatty acids across PubMed, Scopus, and Europe PMC databases. Omega-3 fatty acid supplementation resulted in a significant reduction in overall pruritus severity compared with placebo or vegetable oil interventions. Higher-quality and more standardized studies are required before routine omega-3 fatty acid supplementation can be recommended. However, preliminary evidence suggests that omega-3 supplementation may be beneficial in reducing pruritus severity among patients with CKD-aP.
2026-08-12 | Topical regimens for the management of uremic pruritus
Uremic pruritus (UP), also known as chronic kidney disease-associated pruritus, is a distressing condition affecting patients with end-stage renal disease. Characterized by persistent itching, it significantly impacts patients’ quality of life, leading to sleep disturbances, emotional distress, and decreased overall well-being. Although the exact pathophysiology remains uncertain, immune dysregulation, reduced stratum corneum hydration, and altered neurogenic inflammation contribute to UP. Consequently, treating UP poses a significant challenge. Among therapeutic regimens, topical regimens have been shown to effectively alleviate UP. Various topical formulations, including urea-based, physiological lipids, natural oils, capsaicin, anesthetics and glycerin-containing emollients, have demonstrated benefits in amelioration of pruritic symptoms. Clinical studies suggest that consistent application of emollients can minimize skin dryness and relieve pruritus. This review summarizes key clinical findings on the topical therapeutic regimens for UP.
2026-08-05 | Exploratory Analysis of Pruritus and Sleep Outcomes After LCR35 Supplementation in Maintenance Hemodialysis: A Randomized, Open-Label Controlled Study
Background/Objectives: Uremic pruritus and sleep disturbance commonly coexist in patients receiving maintenance hemodialysis. This analysis examined whether supplementation with Lactobacillus casei var. rhamnosus LCR35 was associated with changes in pruritus and sleep outcomes. Methods: This 12-week randomized, open-label, controlled study included 78 patients receiving maintenance hemodialysis who were assigned to LCR35 supplementation (n = 38; three sachets daily) or usual care without probiotic supplementation (n = 40). No placebo was used. Outcomes were Pittsburgh Sleep Quality Index (PSQI) and 5-D Itch Scale results. We used analysis of covariance (ANCOVA) for between-group analyses, with the week-12 score as the dependent variable and the corresponding baseline score as a covariate. Results: In the LCR35 group, descriptive improvements were observed in the 5-D Itch Scale and selected PSQI outcomes. However, none of the baseline-adjusted between-group differences was statistically significant: for 5-D Itch Scale, −1.48 (95% confidence interval (CI), −3.64 to 0.68; p = 0.176); for global PSQI, −0.80 (95% CI, −2.09 to 0.50; p = 0.225); for PSQI sleep disturbance, −0.07 (95% CI, −0.27 to 0.13; p = 0.482); and use of sleep medications, −0.28 (95% CI, −0.67 to 0.12; p = 0.163). In the LCR35 group, the exploratory association between changes in pruritus and the PSQI sleep-disturbances component was significant before, but not after, false-discovery-rate (FDR) correction (p = 0.007; FDR q = 0.055). Conclusions: Our preliminary findings raised the possibility that LCR35 might modestly influence pruritus and specific sleep disturbances. However, our results do not firmly establish a treatment effect, nor a patient phenotype most likely to benefit.
2026-08-03 | The neuroimmune architecture of uremic pruritus: mechanisms and therapeutic targeting.
Chronic kidney disease-associated pruritus (CKD-aP) remains a prevalent and burdensome symptom whose management is often empirical and only partially effective. Its pathophysiology appears to arise from interacting systemic, cutaneous, neural, and central mechanisms rather than from a single dominant pathway. In this review, we synthesize the evidence for a broader neuroimmune framework encompassing retained uremic solutes, microinflammation, xerosis and barrier dysfunction, immune dysregulation, neuropathic sensitization, opioid imbalance, and neuropeptide signaling. On this basis, we propose a four-node organizing model-Peripheral Neuroimmune Synapse (Node I), Neural Transmission and Hyperexcitability (Node II), Central Opioid Modulation (Node III), and Substance P/NK-1 Amplification (Node IV)-to translate mechanistic complexity into clinically intelligible domains. This model is intended as a pragmatic and hypothesis-generating framework, not as a validated endotyping system. Framed this way, it may help contextualize the observed benefits of therapies such as gabapentinoids and difelikefalin, clarify the limited performance of traditional antihistamine-based strategies, and support a more structured approach to bedside phenotyping and future enrichment-based trials. Prospective validation remains necessary before mechanism-guided therapeutic matching can be recommended as routine clinical practice.
2026-07-24 | Montelukast Versus Gabapentin for Uremic Pruritus in Twice-Weekly Hemodialysis Patients: A 52-Week Prospective Non-Randomized Open-Label Comparative Study.
Uremic pruritus (UP) remains a common and distressing complication in patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis. The burden is particularly pronounced in low- and middle-income countries where twice-weekly hemodialysis is frequently practiced because of resource limitations. Gabapentin is widely used for the treatment of uremic pruritus; however, its use is often limited by central nervous system adverse effects and poor tolerability in older dialysis populations. Montelukast, a leukotriene receptor antagonist with anti-inflammatory properties, has been proposed as a potential alternative therapy. This study aimed to evaluate the comparative efficacy and safety of montelukast versus gabapentin for the treatment of uremic pruritus in patients receiving twice-weekly hemodialysis, with extended follow-up over 52 weeks. This prospective, open-label, non-randomized comparative study enrolled 195 adult patients with refractory uremic pruritus receiving twice-weekly hemodialysis. Participants were allocated to receive either montelukast or gabapentin based on predefined clinical and demographic criteria, including physician discretion and patient-specific factors. Clinical follow-up was conducted at 2, 4, 8, 12, 24, and 52 weeks. Pruritus severity was assessed using the Visual Analogue Scale (VAS). The primary outcome was change in Visual Analogue Scale score from baseline. Secondary outcomes included adverse events, treatment tolerability, need for dose escalation, and treatment discontinuation. A total of 176 patients completed the 52-week follow-up (montelukast, n = 91; gabapentin, n = 85). Baseline pruritus severity was comparable between the montelukast and gabapentin groups (mean VAS score 7.26 ± 1.56 vs. 7.41 ± 1.67, p = 0.54). Both treatments produced significant reductions in Visual Analogue Scale scores from baseline throughout the 52-week follow-up (p < 0.001 for both groups). Dose escalation was required in 38 patients (44.7%) receiving gabapentin within the first 6 weeks of therapy. Adverse events occurred significantly more frequently in the gabapentin group than in the montelukast group; 6 histories of falls and 11 treatment discontinuations due to adverse effects. Frequent adverse events reported in the montelukast group were abdominal pain and headache (17 and 14 episodes, respectively); whereas in the gabapentin group the common side effects were somnolence (39 incidence), fatigue (n = 21), dizziness (n = 17), and cognitive slowing (n = 16). Although gabapentin achieved modestly greater reductions in Visual Analogue Scale scores at selected follow-up time points, the absolute between-group differences remained below the predefined minimum clinically important difference of 1.0 VAS point. Montelukast provided sustained clinically meaningful improvement in uremic pruritus with substantially fewer treatment-related adverse events and superior tolerability than gabapentin. Although gabapentin achieved slightly greater reductions in pruritus severity at selected time points, these differences did not exceed the predefined minimum clinically important difference of 1.0 VAS point. Montelukast represents a practical and well-tolerated therapeutic option for patients receiving twice-weekly hemodialysis, particularly in resource-limited settings.
cell therapies
2025-04-16 | Data Sheet 1_Case Report: Sympathetic nerve block treat chronic kidney disease-associated pruritus.docx
Uremia is the advanced stage of chronic kidney disease (CKD), characterized by the accumulation of metabolic waste products in the blood as a result of the kidneys' inability to meet the body's metabolic demands. Patients with uremia frequently experience a range of complications, including renal anemia, osteoporosis, and cardiovascular disease, all of which significantly impair their quality of life. Chronic kidney disease-associated pruritus (CKD-aP) is a common comorbidity in uremic patients, particularly among those undergoing hemodialysis, with prevalence rates ranging from 10 to 77%. This case report enrolled three patients diagnosed with chronic kidney disease-associated pruritus (CKD-ap) who underwent ultrasound-guided sympathetic nerve blockade procedures. The results demonstrated significant reductions in pruritus intensity concurrent with measurable enhancements in sleep quality and daily functioning.
2019-05-21 | Multipotentials of new asymmetric cellulose triacetate membrane for on-line hemodiafiltration both in postdilution and predilution
On-line hemodiafiltration (OL-HDF) has been generally provided mainly by the postdilution method in Europe and the rest of the world; however, in Japan, it has been provided mostly by the predilution method in order to ameliorate dialysis-related symptoms of dialysis patients by removing larger low molecular weight proteins. This study aimed to elucidate the removal properties of a newly launched asymmetric triacetate (ATA) membrane in OL-HDF both in the postdilution and predilution comparison with other synthetic polymer membranes. Six patients treated by OL-HDF at the Kawashima Hospital Group were randomly chosen for each membrane study. The removal properties of low molecular weight proteins were evaluated by β2-microglobulin (β2-MG), α1-microglobulin (α1-MG), albumin leakage, selective removal index of α1-MG for albumin, and transmembrane pressure for each treatment group. Two types of ATA membrane were evaluated in the study: FIX-S with mild protein permeability and FIX-U with higher protein permeability in the comparisons with other three types of synthetic polymer membranes. The removal rate of β2-MG showed almost no significant differences between the postdilution and predilution methods in most membrane groups at around 75–80% without relations to the membrane material and the substitution volume. The removal rates of α1-MG were markedly different depending on the dilution method of HDF, the membranes, and the substitution volume. Generally, the removal rates of α1-MG were better in the postdilution than the predilution but the selective removals of α1-MG were better in the predilution. The high volume OL-HDF had the risk of excessive albumin leakage in a certain membrane choice. In the FIX series, the removal rates of α1-MG were sufficient both in the postdilution and predilution with the increase of the substitution volume with suppressing the albumin leakage during the dialysis session. Especially, FIX-U showed higher removal of α1-MG with suppressing the albumin leakage. The newly launched ATA membrane could remove α1-MG, selectively suppressing the excessive albumin leakage and increasing the substitution volume safely even in high-volume postdilution. Trial registration: University hospital Medical Information Network (UMIN), UMIN 000035705. Registered 28 January 2019 - Retrospectively registered, https://www.umin.ac.jp/ctr/index-j.htm .
2010-05-01 | Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: Clinical and laboratory long-term follow-up
Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40 patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had four glands removed, while only three glands were found in the remaining two. Perioperative complications consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%). No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37 (86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of 1084 ± 505 pg/ml to 120 ± 381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients. tPTX should be considered a safe and successful procedure for the treatment of severe secondary hyperparathyroidism associated with chronic kidney disease.
antibodies
2026-09-01 | Randomized controlled study of nemolizumab in patients with chronic kidney disease-associated pruritus: NIKAIA-1.
Managing pruritus in hemodialysis patients is challenging. Nemolizumab, a monoclonal antibody targeting IL-31, has demonstrated efficacy in atopic dermatitis and prurigo nodularis with fast reduction of pruritus. To evaluate nemolizumab safety and efficacy for treatment of chronic kidney disease-associated pruritus. This was a 12-week randomized, placebo-controlled study of nemolizumab (30 mg or 60 mg) Q4W in 258 hemodialysis patients with chronic kidney disease-associated pruritus. Endpoints assessed safety, and efficacy on pruritus, sleep disturbances, and quality of life. The primary endpoint (proportion of patients with ≥4-point-improvement in Worst Itch-Numerical Rating Scale at week 12) was not met for either nemolizumab dose (60 mg: 47.7% [P = .0686], 30 mg: 38.5% [P = .37]) versus placebo (32.4%). Patient-reported itch-related quality of life improved on Skindex-10 in the 60 mg group vs placebo (nominal P < .01). Onset of action on itch was rapid. At week 4, ≥4-point-improvement in Worst Itch-Numerical Rating Scale was achieved in 24.3% to 26.6% (nemolizumab) compared with 7.4% (placebo). Adverse events related to study drug were comparable among groups. The primary limitation was the relatively small sample size and duration of follow-up (12 weeks); longer studies would be required to evaluate safety and efficacy of long-term treatment. Although the primary endpoint was not met, the trial demonstrated a favorable safety profile and signals of reduced pruritus and improved itch-related quality of life in patients with chronic kidney disease-associated pruritus over 12 weeks.
2025-10-13 | Real-World Evidence Demonstrating Nemolizumab's Rapid Efficacy in Recalcitrant Uremic Pruritus.
Uremic pruritus is a common and distressing condition in patients with advanced chronic kidney disease (CKD). It often leads to disruption of sleep habits, impaired mental health, and reduced quality of life. Nemolizumab is an interleukin-31 receptor subunit alpha (IL-31R𝛼) antagonist that is currently approved to treat prurigo nodularis (PN) and atopic dermatitis (AD). However, its effectiveness in treating uremic pruritus remains uncertain, as it has only been explored in a limited number of small studies. We present a case of a 69-year-old man on long-term hemodialysis who presented with refractory uremic pruritus. The patient initially reported a pruritus numerical rating scale (NRS) score of 8 out of 10, indicating severe itch on a scale where 0 represents no itch and 10 represents the worst itch imaginable. Despite adequate six-week trials of triamcinolone acetonide 0.1% ointment twice daily, narrowband ultraviolet B (NB-UVB) phototherapy three times weekly, N-acetylcysteine (600 mg twice daily), and gabapentin (300 mg three times daily), his debilitating itch persisted. Consequently, treatment with nemolizumab was initiated. Just two weeks after the initial dose, the patient reported an NRS score of 0, indicating complete relief from pruritus, along with a reduction in excoriated lesions observed on physical examination. The patient reported no side effects from nemolizumab. This case highlights the potential of nemolizumab as an effective and safe treatment option for recalcitrant uremic pruritus. Further exploration of its therapeutic applications in this condition and other vexing-to-treat pruritic conditions is warranted.
2025-09-26 | Dupilumab relieves pruritus both in uremic pruritus and in atopic dermatitis with chronic kidney disease: a retrospective real-world study.
Treatment methods for pruritus in patients with chronic kidney disease (CKD) are lacking. Exploring the therapeutic potential of dupilumab in alleviating pruritus in CKD patients has good clinical value. This retrospective study aims to analyze the effectiveness and safety of dupilumab in atopic dermatitis (AD) patients with CKD and uremic pruritus (UP) patients. Demographic and clinical data from AD patients with CKD stages 3-5 and UP patients who received dupilumab treatment were retrospectively analyzed. Improvements in pruritus were assessed via Peak Pruritus Numerical Rating Scale (PP-NRS) and 5-D itch scale (5-D IS) at weeks 2, 4, 12, and 16. Eczema Area and Severity Index (EASI) and Atopic Dermatitis Control Tool (ADCT) scores were also recorded at week 16 in AD patients with CKD. Safety during treatment was observed. After dupilumab treatment, the PP-NRS and 5D-IS scores of 12 AD patients with CKD and 10 UP patients were significantly decreased. The percentages of UP patients who achieved PP-NRS ≥ 4-point improvement and 5D-IS ≤ 10-point at week 4, 12, and 16 did not significantly differ from those of AD patients with CKD (p > 0.05). At week 16, the skin symptoms in AD patients significantly improved (66.67% achieved EASI-75). No significant adverse effects were found. Dupilumab safely and effectively reduced pruritus in UP patients in the short term and achieved a comparable anti-pruritus effect to AD patients with CKD.
2025-09-10 | Table 1_Dupilumab relieves pruritus both in uremic pruritus and in atopic dermatitis with chronic kidney disease: a retrospective real-world study.docx
Background Treatment methods for pruritus in patients with chronic kidney disease (CKD) are lacking. Exploring the therapeutic potential of dupilumab in alleviating pruritus in CKD patients has good clinical value. Objectives This retrospective study aims to analyze the effectiveness and safety of dupilumab in atopic dermatitis (AD) patients with CKD and uremic pruritus (UP) patients. Methods Demographic and clinical data from AD patients with CKD stages 3–5 and UP patients who received dupilumab treatment were retrospectively analyzed. Improvements in pruritus were assessed via Peak Pruritus Numerical Rating Scale (PP-NRS) and 5-D itch scale (5-D IS) at weeks 2, 4, 12, and 16. Eczema Area and Severity Index (EASI) and Atopic Dermatitis Control Tool (ADCT) scores were also recorded at week 16 in AD patients with CKD. Safety during treatment was observed. Results After dupilumab treatment, the PP-NRS and 5D-IS scores of 12 AD patients with CKD and 10 UP patients were significantly decreased. The percentages of UP patients who achieved PP-NRS ≥ 4-point improvement and 5D-IS ≤ 10-point at week 4, 12, and 16 did not significantly differ from those of AD patients with CKD (p > 0.05). At week 16, the skin symptoms in AD patients significantly improved (66.67% achieved EASI-75). No significant adverse effects were found. Conclusion Dupilumab safely and effectively reduced pruritus in UP patients in the short term and achieved a comparable anti-pruritus effect to AD patients with CKD.
2025-06-25 | Uremic Pruritus: Interleukin-31 as a Target of Therapy in End Stage Renal Disease Patients
AbstractBackground: Uremic pruritus is a prevalent and distressing complication associated with End Stage Renal Disease that can adversely impact quality of life. Uremic pruritus represents one of the skin manifestations seen in End Stage Renal Disease (ESRD). The underlying mechanisms of Uremic pruritus remain incompletely understood; however, it is believed to be driven by multiple factors, including the pruritoceptive theory, local neuropathic processes, the neurogenic theory (which involves dysregulation of the endogenous opioid system), and the immunological theory. Rising serum interleukin-31 level was found in End Stage Renal Disease (ESRD) patients experiencing Uremic pruritus when compared to those without this symptom. Furthermore, interleukin-31 has positive correlation with the intensity of Uremic Pruritus (UP). Various medications have been employed to manage Uremic Pruritus (UP). Treatments such as gabapentin and antihistamines have been effective in alleviating Uremic pruritus (UP) symptoms. Recently, difelikefalin has been introduced as a therapeutic option for Uremic pruritus (UP), demonstrating a notable decrease in the intensity of the condition.Conclusion: The review offers a simplified overview of the pathophysiology of uremic pruritus and its main lines of treatment with their role on reducing pruritus symptoms, It also clarifies the role of interleukin-31 in uremic pruritus and its correlation with severity. The review also suggest the use of interleukin-31 as a novel therapeutic target.
proteins
2025-10-01 | #1744 Impact of kidney transplantation on chronic kidney disease-associated pruritus
Abstract Background and Aims Chronic Kidney Disease-associated Pruritus (CKD-aP), also referred to as uremic pruritus (UP), is a common complication with a prevalence ranging from 18% to 80%, and approximately 40% of patients reporting severe symptoms. Interleukin-31 (IL-31), often termed the “itch cytokine,” has been implicated in the pathogenesis of pruritus in various dermatological disorders. This study aimed to evaluate changes in pruritus severity and serum IL-31 levels before and after kidney transplantation, and to determine the correlation between these parameters. Method A prospective observational study was conducted at Sir Ganga Ram Hospital, New Delhi, involving patients with CKD stage V who were scheduled for renal transplantation. Pruritus was assessed using the 5D Itch Scale, and serum IL-31 levels were measured pre- and post-transplant. A total of 202 patients were screened; 89 of these had pruritus, and 86 were ultimately included in the analysis (after excluding those with primary skin disorders). Results Among the 86 patients with pruritus, 75.5% were male. The dialysis vintage ranged from four preemptive transplants to a maximum of 60 months on dialysis. Mean serum IL-31 levels significantly decreased from 145.02 ± 103.27 pg/mL pre-transplant to 89.91 ± 59.51 pg/mL post-transplant (P < 0.001), alongside a significant reduction in mean 5D itch scores from 15.03 ± 4.36 to 7.44 ± 2.11 (P < 0.001). One month post-transplant, 63.9% of patients reported complete resolution of pruritus, 29.1% had mild pruritus, and 6.9% experienced moderate pruritus. Post-transplant itch scores demonstrated a moderate positive correlation with IL-31 levels (r = 0.411, P = 0.001). Changes in itch scores from pre- to post-transplant also positively correlated with changes in serum IL-31 (r = 0.464, P = 0.001). Conclusion Kidney transplantation leads to a significant reduction in both pruritus severity and serum IL-31 levels in patients with CKD-aP. These findings highlight the potential role of IL-31 as a biomarker for pruritus and offer insights into targeted therapeutic strategies for CKD-associated pruritus.
small molecules
2026-09-18 | Literature Review: How do Omega-3 Fatty Acids Impact Uremic Pruritus in Hemodialysis Patients?
Chronic Kidney Disease-associated Pruritus (CKD-aP) is a debilitating yet often overlooked symptom. Epidemiological studies have shown that up to 40% of patients with chronic kidney disease experience moderate-to-severe pruritus. This condition is also common among patients undergoing hemodialysis. Multiple etiological factors contribute to CKD-aP, including hormonal alterations, neuropathy, increased μ- and κ-opioid receptor activity, and chronic systemic inflammation. Patients with chronic kidney disease are known to experience essential fatty acid deficiency and may therefore benefit from omega-3 fatty acid supplementation, which may help reduce inflammation and improve fatty acid balance. This review was conducted by examining prospective clinical trials investigating the effects of omega-3 fatty acids on CKD-aP that were published in English. A literature search was performed using keywords related to chronic kidney disease, uremic pruritus, dermatology, and omega-3 fatty acids across PubMed, Scopus, and Europe PMC databases. Omega-3 fatty acid supplementation resulted in a significant reduction in overall pruritus severity compared with placebo or vegetable oil interventions. Higher-quality and more standardized studies are required before routine omega-3 fatty acid supplementation can be recommended. However, preliminary evidence suggests that omega-3 supplementation may be beneficial in reducing pruritus severity among patients with CKD-aP.
2026-08-12 | Topical regimens for the management of uremic pruritus
Uremic pruritus (UP), also known as chronic kidney disease-associated pruritus, is a distressing condition affecting patients with end-stage renal disease. Characterized by persistent itching, it significantly impacts patients’ quality of life, leading to sleep disturbances, emotional distress, and decreased overall well-being. Although the exact pathophysiology remains uncertain, immune dysregulation, reduced stratum corneum hydration, and altered neurogenic inflammation contribute to UP. Consequently, treating UP poses a significant challenge. Among therapeutic regimens, topical regimens have been shown to effectively alleviate UP. Various topical formulations, including urea-based, physiological lipids, natural oils, capsaicin, anesthetics and glycerin-containing emollients, have demonstrated benefits in amelioration of pruritic symptoms. Clinical studies suggest that consistent application of emollients can minimize skin dryness and relieve pruritus. This review summarizes key clinical findings on the topical therapeutic regimens for UP.
2026-08-05 | Exploratory Analysis of Pruritus and Sleep Outcomes After LCR35 Supplementation in Maintenance Hemodialysis: A Randomized, Open-Label Controlled Study
Background/Objectives: Uremic pruritus and sleep disturbance commonly coexist in patients receiving maintenance hemodialysis. This analysis examined whether supplementation with Lactobacillus casei var. rhamnosus LCR35 was associated with changes in pruritus and sleep outcomes. Methods: This 12-week randomized, open-label, controlled study included 78 patients receiving maintenance hemodialysis who were assigned to LCR35 supplementation (n = 38; three sachets daily) or usual care without probiotic supplementation (n = 40). No placebo was used. Outcomes were Pittsburgh Sleep Quality Index (PSQI) and 5-D Itch Scale results. We used analysis of covariance (ANCOVA) for between-group analyses, with the week-12 score as the dependent variable and the corresponding baseline score as a covariate. Results: In the LCR35 group, descriptive improvements were observed in the 5-D Itch Scale and selected PSQI outcomes. However, none of the baseline-adjusted between-group differences was statistically significant: for 5-D Itch Scale, −1.48 (95% confidence interval (CI), −3.64 to 0.68; p = 0.176); for global PSQI, −0.80 (95% CI, −2.09 to 0.50; p = 0.225); for PSQI sleep disturbance, −0.07 (95% CI, −0.27 to 0.13; p = 0.482); and use of sleep medications, −0.28 (95% CI, −0.67 to 0.12; p = 0.163). In the LCR35 group, the exploratory association between changes in pruritus and the PSQI sleep-disturbances component was significant before, but not after, false-discovery-rate (FDR) correction (p = 0.007; FDR q = 0.055). Conclusions: Our preliminary findings raised the possibility that LCR35 might modestly influence pruritus and specific sleep disturbances. However, our results do not firmly establish a treatment effect, nor a patient phenotype most likely to benefit.
2026-08-03 | The neuroimmune architecture of uremic pruritus: mechanisms and therapeutic targeting.
Chronic kidney disease-associated pruritus (CKD-aP) remains a prevalent and burdensome symptom whose management is often empirical and only partially effective. Its pathophysiology appears to arise from interacting systemic, cutaneous, neural, and central mechanisms rather than from a single dominant pathway. In this review, we synthesize the evidence for a broader neuroimmune framework encompassing retained uremic solutes, microinflammation, xerosis and barrier dysfunction, immune dysregulation, neuropathic sensitization, opioid imbalance, and neuropeptide signaling. On this basis, we propose a four-node organizing model-Peripheral Neuroimmune Synapse (Node I), Neural Transmission and Hyperexcitability (Node II), Central Opioid Modulation (Node III), and Substance P/NK-1 Amplification (Node IV)-to translate mechanistic complexity into clinically intelligible domains. This model is intended as a pragmatic and hypothesis-generating framework, not as a validated endotyping system. Framed this way, it may help contextualize the observed benefits of therapies such as gabapentinoids and difelikefalin, clarify the limited performance of traditional antihistamine-based strategies, and support a more structured approach to bedside phenotyping and future enrichment-based trials. Prospective validation remains necessary before mechanism-guided therapeutic matching can be recommended as routine clinical practice.
2026-07-24 | Montelukast Versus Gabapentin for Uremic Pruritus in Twice-Weekly Hemodialysis Patients: A 52-Week Prospective Non-Randomized Open-Label Comparative Study.
Uremic pruritus (UP) remains a common and distressing complication in patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis. The burden is particularly pronounced in low- and middle-income countries where twice-weekly hemodialysis is frequently practiced because of resource limitations. Gabapentin is widely used for the treatment of uremic pruritus; however, its use is often limited by central nervous system adverse effects and poor tolerability in older dialysis populations. Montelukast, a leukotriene receptor antagonist with anti-inflammatory properties, has been proposed as a potential alternative therapy. This study aimed to evaluate the comparative efficacy and safety of montelukast versus gabapentin for the treatment of uremic pruritus in patients receiving twice-weekly hemodialysis, with extended follow-up over 52 weeks. This prospective, open-label, non-randomized comparative study enrolled 195 adult patients with refractory uremic pruritus receiving twice-weekly hemodialysis. Participants were allocated to receive either montelukast or gabapentin based on predefined clinical and demographic criteria, including physician discretion and patient-specific factors. Clinical follow-up was conducted at 2, 4, 8, 12, 24, and 52 weeks. Pruritus severity was assessed using the Visual Analogue Scale (VAS). The primary outcome was change in Visual Analogue Scale score from baseline. Secondary outcomes included adverse events, treatment tolerability, need for dose escalation, and treatment discontinuation. A total of 176 patients completed the 52-week follow-up (montelukast, n = 91; gabapentin, n = 85). Baseline pruritus severity was comparable between the montelukast and gabapentin groups (mean VAS score 7.26 ± 1.56 vs. 7.41 ± 1.67, p = 0.54). Both treatments produced significant reductions in Visual Analogue Scale scores from baseline throughout the 52-week follow-up (p < 0.001 for both groups). Dose escalation was required in 38 patients (44.7%) receiving gabapentin within the first 6 weeks of therapy. Adverse events occurred significantly more frequently in the gabapentin group than in the montelukast group; 6 histories of falls and 11 treatment discontinuations due to adverse effects. Frequent adverse events reported in the montelukast group were abdominal pain and headache (17 and 14 episodes, respectively); whereas in the gabapentin group the common side effects were somnolence (39 incidence), fatigue (n = 21), dizziness (n = 17), and cognitive slowing (n = 16). Although gabapentin achieved modestly greater reductions in Visual Analogue Scale scores at selected follow-up time points, the absolute between-group differences remained below the predefined minimum clinically important difference of 1.0 VAS point. Montelukast provided sustained clinically meaningful improvement in uremic pruritus with substantially fewer treatment-related adverse events and superior tolerability than gabapentin. Although gabapentin achieved slightly greater reductions in pruritus severity at selected time points, these differences did not exceed the predefined minimum clinically important difference of 1.0 VAS point. Montelukast represents a practical and well-tolerated therapeutic option for patients receiving twice-weekly hemodialysis, particularly in resource-limited settings.
cell therapies
2025-04-16 | Data Sheet 1_Case Report: Sympathetic nerve block treat chronic kidney disease-associated pruritus.docx
Uremia is the advanced stage of chronic kidney disease (CKD), characterized by the accumulation of metabolic waste products in the blood as a result of the kidneys' inability to meet the body's metabolic demands. Patients with uremia frequently experience a range of complications, including renal anemia, osteoporosis, and cardiovascular disease, all of which significantly impair their quality of life. Chronic kidney disease-associated pruritus (CKD-aP) is a common comorbidity in uremic patients, particularly among those undergoing hemodialysis, with prevalence rates ranging from 10 to 77%. This case report enrolled three patients diagnosed with chronic kidney disease-associated pruritus (CKD-ap) who underwent ultrasound-guided sympathetic nerve blockade procedures. The results demonstrated significant reductions in pruritus intensity concurrent with measurable enhancements in sleep quality and daily functioning.
2019-05-21 | Multipotentials of new asymmetric cellulose triacetate membrane for on-line hemodiafiltration both in postdilution and predilution
On-line hemodiafiltration (OL-HDF) has been generally provided mainly by the postdilution method in Europe and the rest of the world; however, in Japan, it has been provided mostly by the predilution method in order to ameliorate dialysis-related symptoms of dialysis patients by removing larger low molecular weight proteins. This study aimed to elucidate the removal properties of a newly launched asymmetric triacetate (ATA) membrane in OL-HDF both in the postdilution and predilution comparison with other synthetic polymer membranes. Six patients treated by OL-HDF at the Kawashima Hospital Group were randomly chosen for each membrane study. The removal properties of low molecular weight proteins were evaluated by β2-microglobulin (β2-MG), α1-microglobulin (α1-MG), albumin leakage, selective removal index of α1-MG for albumin, and transmembrane pressure for each treatment group. Two types of ATA membrane were evaluated in the study: FIX-S with mild protein permeability and FIX-U with higher protein permeability in the comparisons with other three types of synthetic polymer membranes. The removal rate of β2-MG showed almost no significant differences between the postdilution and predilution methods in most membrane groups at around 75–80% without relations to the membrane material and the substitution volume. The removal rates of α1-MG were markedly different depending on the dilution method of HDF, the membranes, and the substitution volume. Generally, the removal rates of α1-MG were better in the postdilution than the predilution but the selective removals of α1-MG were better in the predilution. The high volume OL-HDF had the risk of excessive albumin leakage in a certain membrane choice. In the FIX series, the removal rates of α1-MG were sufficient both in the postdilution and predilution with the increase of the substitution volume with suppressing the albumin leakage during the dialysis session. Especially, FIX-U showed higher removal of α1-MG with suppressing the albumin leakage. The newly launched ATA membrane could remove α1-MG, selectively suppressing the excessive albumin leakage and increasing the substitution volume safely even in high-volume postdilution. Trial registration: University hospital Medical Information Network (UMIN), UMIN 000035705. Registered 28 January 2019 - Retrospectively registered, https://www.umin.ac.jp/ctr/index-j.htm .
2010-05-01 | Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: Clinical and laboratory long-term follow-up
Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40 patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had four glands removed, while only three glands were found in the remaining two. Perioperative complications consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%). No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37 (86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of 1084 ± 505 pg/ml to 120 ± 381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients. tPTX should be considered a safe and successful procedure for the treatment of severe secondary hyperparathyroidism associated with chronic kidney disease.
antibodies
2026-09-01 | Randomized controlled study of nemolizumab in patients with chronic kidney disease-associated pruritus: NIKAIA-1.
Managing pruritus in hemodialysis patients is challenging. Nemolizumab, a monoclonal antibody targeting IL-31, has demonstrated efficacy in atopic dermatitis and prurigo nodularis with fast reduction of pruritus. To evaluate nemolizumab safety and efficacy for treatment of chronic kidney disease-associated pruritus. This was a 12-week randomized, placebo-controlled study of nemolizumab (30 mg or 60 mg) Q4W in 258 hemodialysis patients with chronic kidney disease-associated pruritus. Endpoints assessed safety, and efficacy on pruritus, sleep disturbances, and quality of life. The primary endpoint (proportion of patients with ≥4-point-improvement in Worst Itch-Numerical Rating Scale at week 12) was not met for either nemolizumab dose (60 mg: 47.7% [P = .0686], 30 mg: 38.5% [P = .37]) versus placebo (32.4%). Patient-reported itch-related quality of life improved on Skindex-10 in the 60 mg group vs placebo (nominal P < .01). Onset of action on itch was rapid. At week 4, ≥4-point-improvement in Worst Itch-Numerical Rating Scale was achieved in 24.3% to 26.6% (nemolizumab) compared with 7.4% (placebo). Adverse events related to study drug were comparable among groups. The primary limitation was the relatively small sample size and duration of follow-up (12 weeks); longer studies would be required to evaluate safety and efficacy of long-term treatment. Although the primary endpoint was not met, the trial demonstrated a favorable safety profile and signals of reduced pruritus and improved itch-related quality of life in patients with chronic kidney disease-associated pruritus over 12 weeks.
2025-10-13 | Real-World Evidence Demonstrating Nemolizumab's Rapid Efficacy in Recalcitrant Uremic Pruritus.
Uremic pruritus is a common and distressing condition in patients with advanced chronic kidney disease (CKD). It often leads to disruption of sleep habits, impaired mental health, and reduced quality of life. Nemolizumab is an interleukin-31 receptor subunit alpha (IL-31R𝛼) antagonist that is currently approved to treat prurigo nodularis (PN) and atopic dermatitis (AD). However, its effectiveness in treating uremic pruritus remains uncertain, as it has only been explored in a limited number of small studies. We present a case of a 69-year-old man on long-term hemodialysis who presented with refractory uremic pruritus. The patient initially reported a pruritus numerical rating scale (NRS) score of 8 out of 10, indicating severe itch on a scale where 0 represents no itch and 10 represents the worst itch imaginable. Despite adequate six-week trials of triamcinolone acetonide 0.1% ointment twice daily, narrowband ultraviolet B (NB-UVB) phototherapy three times weekly, N-acetylcysteine (600 mg twice daily), and gabapentin (300 mg three times daily), his debilitating itch persisted. Consequently, treatment with nemolizumab was initiated. Just two weeks after the initial dose, the patient reported an NRS score of 0, indicating complete relief from pruritus, along with a reduction in excoriated lesions observed on physical examination. The patient reported no side effects from nemolizumab. This case highlights the potential of nemolizumab as an effective and safe treatment option for recalcitrant uremic pruritus. Further exploration of its therapeutic applications in this condition and other vexing-to-treat pruritic conditions is warranted.
2025-09-26 | Dupilumab relieves pruritus both in uremic pruritus and in atopic dermatitis with chronic kidney disease: a retrospective real-world study.
Treatment methods for pruritus in patients with chronic kidney disease (CKD) are lacking. Exploring the therapeutic potential of dupilumab in alleviating pruritus in CKD patients has good clinical value. This retrospective study aims to analyze the effectiveness and safety of dupilumab in atopic dermatitis (AD) patients with CKD and uremic pruritus (UP) patients. Demographic and clinical data from AD patients with CKD stages 3-5 and UP patients who received dupilumab treatment were retrospectively analyzed. Improvements in pruritus were assessed via Peak Pruritus Numerical Rating Scale (PP-NRS) and 5-D itch scale (5-D IS) at weeks 2, 4, 12, and 16. Eczema Area and Severity Index (EASI) and Atopic Dermatitis Control Tool (ADCT) scores were also recorded at week 16 in AD patients with CKD. Safety during treatment was observed. After dupilumab treatment, the PP-NRS and 5D-IS scores of 12 AD patients with CKD and 10 UP patients were significantly decreased. The percentages of UP patients who achieved PP-NRS ≥ 4-point improvement and 5D-IS ≤ 10-point at week 4, 12, and 16 did not significantly differ from those of AD patients with CKD (p > 0.05). At week 16, the skin symptoms in AD patients significantly improved (66.67% achieved EASI-75). No significant adverse effects were found. Dupilumab safely and effectively reduced pruritus in UP patients in the short term and achieved a comparable anti-pruritus effect to AD patients with CKD.
2025-09-10 | Table 1_Dupilumab relieves pruritus both in uremic pruritus and in atopic dermatitis with chronic kidney disease: a retrospective real-world study.docx
Background Treatment methods for pruritus in patients with chronic kidney disease (CKD) are lacking. Exploring the therapeutic potential of dupilumab in alleviating pruritus in CKD patients has good clinical value. Objectives This retrospective study aims to analyze the effectiveness and safety of dupilumab in atopic dermatitis (AD) patients with CKD and uremic pruritus (UP) patients. Methods Demographic and clinical data from AD patients with CKD stages 3–5 and UP patients who received dupilumab treatment were retrospectively analyzed. Improvements in pruritus were assessed via Peak Pruritus Numerical Rating Scale (PP-NRS) and 5-D itch scale (5-D IS) at weeks 2, 4, 12, and 16. Eczema Area and Severity Index (EASI) and Atopic Dermatitis Control Tool (ADCT) scores were also recorded at week 16 in AD patients with CKD. Safety during treatment was observed. Results After dupilumab treatment, the PP-NRS and 5D-IS scores of 12 AD patients with CKD and 10 UP patients were significantly decreased. The percentages of UP patients who achieved PP-NRS ≥ 4-point improvement and 5D-IS ≤ 10-point at week 4, 12, and 16 did not significantly differ from those of AD patients with CKD (p > 0.05). At week 16, the skin symptoms in AD patients significantly improved (66.67% achieved EASI-75). No significant adverse effects were found. Conclusion Dupilumab safely and effectively reduced pruritus in UP patients in the short term and achieved a comparable anti-pruritus effect to AD patients with CKD.
2025-06-25 | Uremic Pruritus: Interleukin-31 as a Target of Therapy in End Stage Renal Disease Patients
AbstractBackground: Uremic pruritus is a prevalent and distressing complication associated with End Stage Renal Disease that can adversely impact quality of life. Uremic pruritus represents one of the skin manifestations seen in End Stage Renal Disease (ESRD). The underlying mechanisms of Uremic pruritus remain incompletely understood; however, it is believed to be driven by multiple factors, including the pruritoceptive theory, local neuropathic processes, the neurogenic theory (which involves dysregulation of the endogenous opioid system), and the immunological theory. Rising serum interleukin-31 level was found in End Stage Renal Disease (ESRD) patients experiencing Uremic pruritus when compared to those without this symptom. Furthermore, interleukin-31 has positive correlation with the intensity of Uremic Pruritus (UP). Various medications have been employed to manage Uremic Pruritus (UP). Treatments such as gabapentin and antihistamines have been effective in alleviating Uremic pruritus (UP) symptoms. Recently, difelikefalin has been introduced as a therapeutic option for Uremic pruritus (UP), demonstrating a notable decrease in the intensity of the condition.Conclusion: The review offers a simplified overview of the pathophysiology of uremic pruritus and its main lines of treatment with their role on reducing pruritus symptoms, It also clarifies the role of interleukin-31 in uremic pruritus and its correlation with severity. The review also suggest the use of interleukin-31 as a novel therapeutic target.
proteins
2025-10-01 | #1744 Impact of kidney transplantation on chronic kidney disease-associated pruritus
Abstract Background and Aims Chronic Kidney Disease-associated Pruritus (CKD-aP), also referred to as uremic pruritus (UP), is a common complication with a prevalence ranging from 18% to 80%, and approximately 40% of patients reporting severe symptoms. Interleukin-31 (IL-31), often termed the “itch cytokine,” has been implicated in the pathogenesis of pruritus in various dermatological disorders. This study aimed to evaluate changes in pruritus severity and serum IL-31 levels before and after kidney transplantation, and to determine the correlation between these parameters. Method A prospective observational study was conducted at Sir Ganga Ram Hospital, New Delhi, involving patients with CKD stage V who were scheduled for renal transplantation. Pruritus was assessed using the 5D Itch Scale, and serum IL-31 levels were measured pre- and post-transplant. A total of 202 patients were screened; 89 of these had pruritus, and 86 were ultimately included in the analysis (after excluding those with primary skin disorders). Results Among the 86 patients with pruritus, 75.5% were male. The dialysis vintage ranged from four preemptive transplants to a maximum of 60 months on dialysis. Mean serum IL-31 levels significantly decreased from 145.02 ± 103.27 pg/mL pre-transplant to 89.91 ± 59.51 pg/mL post-transplant (P < 0.001), alongside a significant reduction in mean 5D itch scores from 15.03 ± 4.36 to 7.44 ± 2.11 (P < 0.001). One month post-transplant, 63.9% of patients reported complete resolution of pruritus, 29.1% had mild pruritus, and 6.9% experienced moderate pruritus. Post-transplant itch scores demonstrated a moderate positive correlation with IL-31 levels (r = 0.411, P = 0.001). Changes in itch scores from pre- to post-transplant also positively correlated with changes in serum IL-31 (r = 0.464, P = 0.001). Conclusion Kidney transplantation leads to a significant reduction in both pruritus severity and serum IL-31 levels in patients with CKD-aP. These findings highlight the potential role of IL-31 as a biomarker for pruritus and offer insights into targeted therapeutic strategies for CKD-associated pruritus.
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Drug Discovery Landscape
1 orphan drug designation for Uremic pruritus.
1 orphan drug designation for Uremic pruritus.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
(-)-17-(cyclopropylmethyl)-3,14 ß-dihydroxy-4,5 α-epoxy-6ß-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride | small molecules | EMA | Toray International Europe GmbH |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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