Chronic Kidney Disease-associated Pruritus Research Articles

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.

Chronic Kidney Disease-Associated Pruritus: A Glance at Novel and Lesser-Known Treatments.

Chronic kidney disease-associated pruritus (CKD-aP), also known as uremic pruritus, has been associated with increased mortality and lower quality of life among patients with chronic kidney disease (CKD). The relentless nature of the condition is mainly due to its diverse and complex etiologies, which are still being studied. Despite the introduction of many agents to treat it, the resolution rates of CKD-aP still remain unsatisfactory. This study sought to review the lesser-known/novel treatments and establish a relationship between their mechanism of action and the proposed etiologies implicated in CKD-aP. We also discuss the role of dialysis modification in managing CKD-aP.A decent proportion of the reviewed studies have proposed that the agents analyzed in them act through hampering inflammation. Interestingly, the results of two agents alluded to the role of dysbiosis in CKD-aP. The addition of hemoperfusion to the dialysis regimen of patients with CKD-aP improved the severity of their symptoms.The featured treatments could be tried in patients with intractable symptoms. However, additional research is needed to confirm the findings reported in these studies. A better understanding of the pathologic mechanisms is required to help guide the development of agents that can better treat CKD-aP.

The impact of underlying diseases-related drugs on the chronic kidney disease-associated pruritus in hemodialysis patients.

Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) is a frequent compromising symptom in end-stage renal disease. Despite the little attention paid to drugs used among hemodialysis (HD) patients, investigating medications used in this population of patients and examining the status of CKD-aP may lead to the identification of medications that improve or worsen the pruritus condition. We aimed to assess the role of underlying diseases-related drugs on CKD-aP in HD patients. We performed a case - control study on HD patients aged over 18 years old. The demographic data and clinical parameters including HD parameters, drug history, dermatologic assessments, and laboratory examination were assessed. We compared 128 patients with CKD-aP as cases and 109 patients without CKD-aP as controls. Cases were on the longer course of dialysis (44.69 ± 43.24 months for cases vs. 38.87 ± 50.73 months for controls; P = 0.02). In multiple analyses of variables related to CKD-aP, backward LR logistic regression revealed that only atorvastatin (P = 0.036) was considered to be a predictive factor associated with CKD-aP. Thus, the use of atorvastatin reduced the index of CKD-aP (95% confidence interval: 0.256-0.954, odd's Ratio = 0.494). Atorvastatin was associated with decreased frequencies of CKD-aP among HD patients in our study. This knowledge may guide further clinical trials to evaluate atorvastatin's immunomodulatory and anti-inflammatory effects on the CKD-aP in HD populations.

POSA180 Real-World Therapeutic Patterns of Patients in Haemodialysis Affected By Chronic Kidney Disease-Associated Pruritus: An Italian Administrative Database Analysis

To evaluate therapeutic patterns and integrated costs of patients in haemodialysis with/without chronic kidney disease-associated pruritus (CKD-aP) from the Italian National Health Service (INHS) perspective.

POSC312 A Methodological Approach to Assess the Economic Value of Difelikefalin to Treat Chronic Kidney Disease Associated Pruritus (CKD-AP)

Patients in end-stage renal disease receiving haemodialysis frequently experience CKD-aP which is associated with increased risk of depression, poor sleep, and reduced health related quality of life (HRQoL). A new compound, difelikefalin (DFK) was tested in two Phase-III studies (KALM 1&2), showing reduced CKD-aP intensity and improved dermatological HRQoL. KALM were double blind placebo controlled for 12 weeks and continued as open label extension up to 52 weeks (OLE) where placebo (PBO) patients switched to DFK.

Unravelling the pathophysiology of chronic kidney disease-associated pruritus.

ABSTRACTFor decades, itch related to chronic kidney disease (CKDaP) has been a clinical problem, but the aetiology and pathophysiology of CKDaP are still not yet fully understood—currently the underlying pathophysiological mechanisms are thought to be multifactorial. As new therapeutic targets have recently been identified and clinical trials have shown promising results, our current understanding of the interrelationships has expanded significantly. Here we review the pathophysiology and recent findings on modulation and sensitization of itch contributing to the development of CKDaP, covering hypothesis regarding immune system dysfunction, metabolic changes, uremic toxin deposition, peripheral neuropathy and imbalances in the endogenous opioid system.

Psychometric validation and meaningful change thresholds of the Worst Itching Intensity Numerical Rating Scale for assessing itch in patients with chronic kidney disease-associated pruritus

BackgroundChronic kidney disease-associated pruritus (CKD-aP) is characterized by persistent itch that often leads to substantially impaired quality of life. The Worst Itching Intensity Numerical Rating Scale (WI-NRS) is a single-item patient-reported outcome measure in which patients indicate the intensity of the worst itching they experienced over the past 24 h. Here, we evaluated the content validity and psychometric properties of the WI-NRS and confirmed the threshold of meaningful change in hemodialysis patients with moderate-to-severe CKD-aP.MethodsContent validity interviews were conducted in 23 patients. Psychometric properties of the WI-NRS were assessed using data from one phase 2 (N = 174) and two phase 3 (N = 848) clinical trials investigating an anti-pruritic treatment. Anchor-based methods were used to confirm meaningful within-patient change score thresholds in the phase 3 trial patients and mixed-method exit interviews (N = 70) contributed further insight.ResultsContent validity interviews indicated patients considered the WI-NRS to be straightforward, comprehensive, and relevant. Test–retest reliability was strong in both trial cohorts (intraclass correlation coefficients > 0.75). Construct validity analyses indicated high correlation between the WI-NRS and other measures of itch. Anchor-based analyses showed a reduction of ≥ 3 points from baseline score represented an appropriate clinically meaningful within-patient change on the WI-NRS. In the exit interviews, all patients with a reduction ≥ 3 points considered the change meaningful.ConclusionsThe WI-NRS is a reliable, valid, and responsive measure of itch intensity for patients with moderate-to-severe CKD-aP. These results support its use to assess treatment efficacy and in clinical evaluation and management of pruritus in hemodialysis patients.

Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches.

ABSTRACTChronic kidney disease (CKD)-associated pruritus (CKD-aP) is an underdiagnosed yet severely distressing condition that impacts 60% of patients on dialysis and many nondialysis patients with Stages 3–5 CKD. However, despite its high prevalence, there are currently limited treatment options available for these patients and a lack of treatment guidelines for clinicians. In this manuscript, we reviewed the available literature in order to evaluate the current management and treatment options for CKD-aP, including dialysis management, topical treatments, gabapentinoids, opioids and alternative medicine. We also review the available data on CKD-aP treatments in development and propose new guidelines for managing patients with CKD-aP.

Epidemiology and burden of chronic kidney disease-associated pruritus.

ABSTRACTChronic kidney disease–associated pruritus (CKD-aP) is a common, yet underrecognized condition in patients with CKD and end-stage kidney disease (ESKD). Real-world observational studies indicate that CKD-aP affects up to 80% of ESKD patients undergoing haemodialysis (HD), with ∼40% experiencing moderate to severe itch. CKD-aP can negatively impact patients’ mental and physical health-related quality of life (HRQoL) and is also associated with sleep disturbance and depression. Several studies have found that CKD-aP is a predictor of adverse medical outcomes, including an increased risk of hospitalizations and mortality. In this article we review the literature relating to the epidemiology of CKD-aP to describe its prevalence across the treatment spectrum of CKD (non-dialysis, HD, peritoneal dialysis and transplant recipients) and to summarize potential risk factors associated with its development. We also review key data from studies that have evaluated the impact of CKD-aP on HRQoL and medical outcomes.

Do you feel itchy? A guide towards diagnosis and measurement of chronic kidney disease-associated pruritus in dialysis patients.

ABSTRACTChronic kidney disease-associated pruritus (CKD-aP) is a potentially distressing condition that affects a significant proportion of patients with end-stage kidney disease undergoing dialysis. CKD-aP may lead to worsening of patients’ physical and mental health-related quality of life (HRQoL) and has also been linked with worse clinical outcomes, including increased mortality. Despite these detrimental effects, evidence from real-world studies shows that CKD-aP still remains overlooked by nephrologists and underreported by patients in clinical practice. Itch is subjective and therefore its diagnosis is often dependent on patients reporting this symptom. There is an opportunity to reduce the burden of CKD-aP on dialysis patients by increasing awareness about this condition and the availability of effective treatments. It is particularly important that nephrologists and other healthcare providers routinely ask their patients if they are experiencing itch. The differential diagnosis of CKD-aP requires a step-by-step identification and exclusion of possible alternative or concomitant causes of itch. Several simple validated self-reported assessment scales are available to evaluate the presence and severity of itch in a time-efficient manner, making them suitable for use in everyday clinical practice. The impact of CKD-aP on haemodialysis patients’ HRQoL should also be assessed on a regular basis. This review provides a comprehensive overview of the differential diagnosis of CKD-aP and the diagnostic tools that are available to identify itch and quantify its severity and impact on patient HRQoL. A suggested algorithm to guide the screening, diagnosis and assessment of CKD-aP among dialysis patients in real-world practice is provided.

Use of Sertraline in Hemodialysis Patients.

Depression and anxiety are the most common psychiatric disorders in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) and may correlate with lower quality of life and increased mortality. Depression treatment in HD patients is still a challenge both for nephrologists and psychiatrists. The possible treatment of depressive disorders can be pharmacological and non-pharmacological. In our article, we focus on the use of sertraline, the medication which seems to be relatively safe and efficient in the abovementioned population, taking under consideration several limitations regarding the use of other selective serotonin reuptake inhibitors (SSRIs). In our paper, we discuss different aspects of sertraline use, taking into consideration possible benefits and side effects of drug administration like impact on QTc (corrected QT interval) prolongation, intradialytic hypotension (IDH), chronic kidney disease-associated pruritus (CKD-aP), bleeding, sexual functions, inflammation, or fracture risk. Before administering the medication, one should consider benefits and possible side effects, which are particularly significant in the treatment of ESRD patients; this could help to optimize clinical outcomes. Sertraline seems to be safe in the HD population when provided in proper doses. However, we still need more studies in this field since the ones performed so far were usually based on small samples and lacked placebo control.

Chronic kidney disease-associated pruritus: features and associated factors

Chronic kidney disease-associated pruritus: features and associated factors

Topical Application of Glycerine – Paraffin Combination in CKD-associated Pruritus and Uremic Xerosis: Study Protocol for a Randomized Control Trial

Background: Chronic kidney disease associated pruritus (CKD-ap) and xerosis is intensely annoying and unpleasant manifestations associated with maintenance renal dialysis (MRD) among chronic kidney disease (CKD) patients. It severely compromises the quality of life by disturbing normal sleep pattern and also adversely affect the mental health in CKD patients. Many proposed treatment plan for CKD –ap is tested but none of the treatment plan provide complete relief from itch associated with MRD. Glycerine accelerate barrier repair and also has rapid hydrating and smoothing effect while Paraffin preserve the barrier function against irritant. As a comparator Mustard oil is used as it is commonly used home remedy by people in Indian sub-continent for dry skin.&#x0D; Objectives: The primary objective of the study is to compare the efficacy of Glycerine –paraffin combination with mustered oil on skin related quality of life among CKD patients with CKD-ap and xerosis.&#x0D; Methodology: A randomised, single blind, controlled, clinical trial intending to investigate and compare the efficacy of Glycerine – Paraffin combination with mustard oil in CKD –ap and xerosis and overall SRQOL among CKD patients. The study aims to enrol 140 CKD patients having moderate to severe CKD-ap and xerosis by using GI gammal score (standardized tool for assessment of xerosis). They will be randomly distributed among 2 parallel group, experimental &amp; control group. Allocation concealment will be maintained by using SNOSE technique. Experimental group will be instructed to apply glycerine paraffin combination and mustard oil to control group twice a day for 4 weeks. participant will be evaluated for xerosis and pruritus score at baseline, day 7, day 28 and day 56. Scores of SRQOL will be assessed at baseline and on 56 days. &#x0D; Conclusion: The RCT aims to identify &amp; compare the efficacy of Glycerine –paraffin combination with mustard oil on skin related quality of life among CKD patients with CKD-ap and xerosis.

Chronic Kidney Disease-Associated Pruritus

Pruritus is a distressing condition associated with end-stage renal disease (ESRD), advanced chronic kidney disease (CKD), as well as maintenance dialysis and adversely affects the quality of life (QOL) of these patients. It has been reported to range from 20% to as high as 90%. The mechanism of CKD-associated pruritus (CKD-aP) has not been clearly identified, and many theories have been proposed to explain it. Many risk factors have been found to be associated with CKD-aP. The pruritus in CKD presents with diverse clinical features, and there are no set features to diagnose it.The patients with CKD-aP are mainly treated by nephrologists, primary care doctors, and dermatologists. Many treatments have been tried but nothing has been effective. The search of literature included peer-reviewed articles, including clinical trials and scientific reviews. Literature was identified through March 2021, and references of respective articles and only articles published in the English language were included.

Chronic kidney disease-associated pruritus significantly impacts on quality of life of patients on haemodialysis and associates with increased levels of serum calcium and phosphorus

Purpose of the studyChronic kidney disease-associated pruritus (CKD-aP) is common among patients on maintenance haemodialysis (HD). We performed a study to explore the clinical features of patients with CKD-aP and...

Comparative Analysis of Chronic Kidney Disease-Associated Pruritus: A Multi-Ethnic Study among Patients on Hemodialysis

To date, no study has compared the prevalence of chronic kidney disease-associated pruritus (CKD-aP) among patients on hemodialysis in Pakistan (a developing country with poor health resources) and Malaysia (a newly industrialized country with adequate health resources). The aim was to compare CKD-aP between Pakistani and Malaysian patients on hemodialysis and factors associated with CKD-aP. Pakistani patients were recruited from July 2016 to April 2017 from two tertiary hospitals in Peshawar an

Western and complementary alternative medicine treatment of uremic pruritus: A literature review.

Uremic pruritus (UP), also called chronic kidney disease-associated pruritus (CKD-aP), is a bothersome symptom that causes sleep disturbance, anxiety, depression, and reduced quality of life. Pruritus often occurs in patients with end-stage renal disease. There is still no definite treatment for UP due to its unclear pathogenesis. We searched electronic databases (PubMed and Google Scholar) and gathered the latest clinical trials and pilot studies of Western and complementary alternative medicine (CAM) therapies for UP in English. These UP studies were separated into three main groups: systemic, topical, and others and CAM. Gabapentin, nalfurafine, acupuncture, and Chinese herbal bath therapy (CHBT) show antipruritic effects, with higher evidence grades in the meta-analysis. Emollients with additive compounds are more effective for reducing itch than emollients without additives. Supplements for deficient elements, such as zinc, omega-3, and omega-6, also show benefits for pruritus improvement. CAM therapies such as acupuncture, herbs, and herbal baths or creams all have good results for UP treatment. We summarize the treatments and suggest a treatment algorithm for UP according to severity. Some UP therapies are already supported by large-scale clinical evidence, and some new treatments can provide patients with new hope and treatment options. However, these new methods still need large population studies and further exploration.

An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease

ABSTRACT Introduction: Chronic kidney disease-associated pruritus (CKD-aP), or uremic pruritus, is a severely distressing condition that occurs in greater than 60% of patients undergoing dialysis. However, there are currently no FDA approved treatments for CKD-aP in the United States or Europe. Difelikefalin (DFK) is a kappa opioid receptor agonist with limited central nervous system (CNS) penetration that aims to fill this void by effectively and safely reducing itch in these patients. Areas covered: Through a review of the current literature (using PubMed and Google Scholar keyword searches of difelikefalin, CR845, pruritus, itch, opioids, hemodialysis, chronic kidney disease, uremic pruritus), the authors review DFK’s mechanism of action and use published clinical trial data to evaluate its effectiveness in treating CKD-aP both individually and comparatively to other treatment alternatives. Expert opinion: DFK’s IV formulation seems to provide safe, rapid-acting and effective itch reduction in hemodialysis patients without many of the negative mu opioid receptor (MOR)- or CNS- related side effects or drug-drug interactions of other currently available opioids. Its administration through IV bolus immediately after dialysis sessions at dialysis centers also increases availability to and ease of drug scheduling for this target population.

Clinically meaningful change in itch intensity scores: An evaluation in patients with chronic kidney disease–associated pruritus

Clinically meaningful change in itch intensity scores: An evaluation in patients with chronic kidney disease–associated pruritus

A randomized controlled study of 6% gabapentin topical formulation for chronic kidney disease-associated pruritus.

Novel agents with good safety profiles are needed in the management of chronic kidney disease-associated pruritus (CKD-AP). This study aims to assess the efficacy and safety of topical gabapentin in the treatment of CKD-AP. The authors conducted a randomized, double-blind, vehicle-controlled study. The key inclusion criteria were: (i) patients on hemodialysis for at least 8weeks, and (ii) a baseline visual analog scale (VAS) pruritus score ≥5. Patients were randomized into two groups. Topical 6% gabapentin was used in the experimental group while plain permeation cream was used for the control group. The primary endpoint was the mean change in pruritus scores using the VAS (MCPS-VAS) from baseline after 1 and 2weeks of once daily application. Thirty patients (15 per group) were included in the analysis. Treatment with 6% topical gabapentin resulted in significantly decreased mean pruritus scores at 1week (mean score 2.7; range 0-5; P<0.001) and 2weeks (mean score 1.3, range 0-5; P<0.001) from baseline (mean score 5.9; range 5-8). The MCPS-VAS of the two groups were not significantly different (P=0.8) after 1week. However, the MCPS-VAS of the experimental group (mean change -4.6; range 0-7) was significantly greater (P=0.01) compared to control (mean change -2.6; range -1 to 5) after 2weeks. There were no drug-related adverse events reported. Our results suggest that short-term use of topical gabapentin may significantly decrease CKD-AP severity after 2weeks with no reported acute adverse events.