Chronic Kidney Disease-associated Pruritus Research Articles

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.
 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.
 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 & 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. 
 Conclusion: The RCT aims to identify & 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.

Evaluation of Efficacy of Mirtazapine on Pruritus and Serum Histamine and Serotonin Levels in Patients Undergoing Hemodialysis: A Before-After Pilot Clinical Trial.

BackgroundAlthough chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and frustrating symptom in patients with advanced kidney diseases, its optimal treatments are not well defined. Based on its mechanism of action, as a histamine-1 (H1), 5-(hydroxytryptamine) HT2, and 5HT3-receptor blocker, mirtazapine may be effective in the treatment of CKD-aP. Hence, this study aimed to investigate the efficacy of mirtazapine for the treatment of pruritus in patients undergoing hemodialysis (HD).MethodsA before–after clinical trial was conducted from September 2018 until March 2019, on 30 HD-patients that had been referred to the HD ward of a tertiary hospital, in Hamadan, Iran. After the 2-week washout period, mirtazapine was administered with a dosage of 15 mg/day for an additional 2 weeks. At baseline and at each dialysis session, the effects of the mirtazapine on the pruritus severity based on the visual analogue scale (VAS) and degree of sleep interference resulting from the pruritus were asked and recorded. Additionally, at the baseline and the end of 2 weeks of treatment, the serum histamine and serotonin levels, as the main chemical pruritogens evoking pruritus symptoms, were also determined.ResultsTwenty-seven patients completed the entire course of the study. Based on the general linear model analysis, a progressive decline in the mean VAS score was observed over time during the study. The mean VAS score decreased from 8.48 ± 1.01 at baseline to 1.04 ±0.79 at the end of treatment (P-value<0.001). Similarly, the mean sleep interference scores were also significantly improved throughout treatment (decreased from 8.07±1.43 to 2.81± 0.74; P-value<0.001). Further, at the end of the treatment, a noticeable decrement in the serum histamine level was also seen (P-value = 0.006). The drug was acceptably well-tolerated and a majority of the patients were satisfied with this treatment.ConclusionThis pilot study suggests that mirtazapine may be an effective treatment option for the management of CKD-aP. However, further studies would be needed to confirm these results.

Epidemiology of Chronic Kidney Diseases (CKD) in Malaysia and Pakistan, Pathophysiology of CKD-Associated Pruritus and Other CKD-Associated Dermatological Disorders

Almost 50–90% of chronic kidney disease patients undergoing haemodialysis have been reported to have Chronic kidney disease-associated pruritus (CKD-aP). The intensity of CKD-aP may vary from a mild itch to an unbearable pruritic sensation which interferes with the patient’s quality of life. CKD-aP has become one of the upmost distressing cutaneous and most common symptom of chronic kidney disease which is often overlooked by nephrologists, primary care physicians, and other health-care professionals. Typically sleep disorders, mental and social well-being have been correlated with chronic kidney disease patients. With that this article presents vital comprehensive review which includes epidemiology of chronic kidney disease in Malaysia and Pakistan, CKD-associated pruritus and other dermatological disorders associated with chronic kidney diseases, pathophysiology of CKD-associated pruritus, clinical features of chronic kidney disease-associated pruritus, diagnosis of CKD-associated uremic pruritus, differential diagnosis of CKD-associated uremic pruritus, assessment and quantification of pruritus severity.

Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus.

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

PUK28 EMULATING EQ-5D DATA FROM AVAILABLE PROS TO OPTIMIZE CLINICAL TRIAL PLANNING IN CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS

We aimed to assess the expected sensitivity of EQ-5D-5L in a multi-morbid patient population on hemodialysis (HD) suffering from moderate or severe chronic kidney disease-associated pruritus (CKD-aP) to inform design and sample size calculation for a phase-3-study intended to collect payer-relevant quality of life (QoL) data. Using available patient-level data from a phase-2-study (CR845-CLIN2101) in 174 CKD-aP patients treated with difelikefalin (DFK) 0.5, 1.0, and 1.5 mcg/kg or placebo that collected itch intensity, Skindex-10 and 5D-Itch Scale, we emulated EQ-5D-5L health states by matching related questions from available patient-reported outcomes (PRO) instruments to the relevant EQ-5D dimension and applied the United Kingdom (UK) valuation set. To account for differences in the questions and rating scales used in each instrument, different mapping scenarios were assessed. Treatment with DFK resulted in a statistically significant 8.2 point higher improvement on the Skindex-10 and of 2.5 points on the 5D-Itch scale (both p<0.001 versus placebo). Depending on the mapping applied to emulate EQ-5D-5L health states, this translated into improved QoL scores of 0.1 to 0.21 based on the UK tariff. Emulated QoL scores are similar to those directly measured with EQ-5D-5L in HD patients in other studies, supporting the validity of the results. This emulation increased the confidence in the ability of EQ-5D-5L to detect relevant differences in patients’ utilities when treating CKD-aP, despite potential confounding by the underlying morbidity. While these results do not allow to claim any actual effect on patients’ utility, the quantification of the magnitude of the expected effect helped to appropriately power the future studies in the absence of any analogue cases.

What are new treatment concepts in systemic itch?

Chronic pruritus is a relevant symptom burden in various systemic diseases. It is most commonly observed in patients with chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reaction. Recent basic research has unravelled novel treatment targets which are currently in preclinical phases, clinical trials or have already been licensed. While µ-opioid receptor antagonists have been used since decades mainly in cholestatic pruritus, the k-opioid receptor agonist nalfurafine has been licensed in Japan for chronic kidney disease-associated pruritus (CKDaP) as well as cholestatic pruritus. Further κ-opioid receptor agonists are currently investigated in various clinical trials including CKDaP. In recent years, the calcium channel blockers gabapentin and pregabalin have also been recognized as effective anti-pruritus therapy in several internal diseases with the best evidence in chronic kidney disease-associated pruritus. Neurokinin-1 receptor antagonists have been investigated with variable benefit in CKDaP, solid tumors and lymphoproliferative disorders such as cutaneous T-cell lymphoma, Sézary syndrome. Inhibitors of the ileal bile acid transporter (IBAT) represent a selective interruption of the enterohepatic circulation and are currently investigated in various hepatobiliary disorders associated with pruritus. The current development and testing of novel drugs in clinical trials offers hope to struggling physicians and suffering patients.

Pruritus Associated With Chronic Kidney Disease: A Comprehensive Literature Review.

The prevalence of pruritus in chronic kidney disease (CKD) patients has varied over the years, and some studies suggest the prevalence may be coming down with more effective dialysis. Chronic kidney disease-associated pruritus (CKD-aP), previously called uremic pruritus, is a distressing symptom experienced by patients with mainly advanced chronic kidney disease. CKD-aP is associated with poor quality of life, depression, anxiety, sleep disturbance, and increased mortality. The incidence of CKD-aP is decreasing given improvements in dialysis treatments, but approximately 40% of patients with end-stage renal disease experience CKD-aP. While the pathogenesis of CKD-aP is not well understood, the interaction between non-myelinated C fibers and dermal mast cells plays an important role in precipitation and sensory stimulation. Other causes of CKD-aP include metabolic abnormalities such as abnormal serum calcium, parathyroid, and phosphate levels; an imbalance in opiate receptors is also an important factor. CKD-aP usually presents as large symmetric reddened areas of skin, often at night. Managing CKD-aP is a challenge. Research in this area is difficult because most studies are not comparable given their small group samples, study designs, and lack of standardized study measures. The most commonly used treatment is a combination of narrow-band ultraviolet B phototherapy and a μ-opioid receptor antagonist such as naltrexone.

Changes in prevalence and severity of chronic kidney disease-associated pruritus over 6 years in a community hemodialysis clinic: a retrospective observational study

We compared the status of chronic kidney disease-associated pruritus among outpatients of a hemodialysis (HD) clinic in 2008 and 2014, using identical questionnaires. All outpatients receiving HD participated in the study. The prevalence of pruritus over the week before questionnaire administration was not significantly different between 2008 (58.6%) and 2014 (50.0%). However, the percentage of patients with moderate to extreme itch decreased from 48.5% to 29.0% (P&lt;0.01). The rate of patient satisfaction with the antipruritic treatment increased from 22.6% to 68.0% (P&lt;0.01). Our experience may encourage physicians to modify antipruritic treatments for better patient care.

Strong Associations Between Inflammation, Pruritus and Mental Health in Dialysis Patients.

Pruritus, impaired mental health and inflammation contribute to morbidity in end-stage renal disease. There are no studies on all 3 conditions. We therefore obtained inflammatory parameter data (C-reactive protein and interleukin-6), pruritus data and psychological test data (36-Item Short-Form Health Survey, "Allgemeine Depressionsskala" and Toronto Alexithymia Scale-20) for 19 dialysis patients with pruritus, 20 dialysis patients without pruritus and 15 healthy controls. Non-parametric hierarchical clustering revealed 3 clusters of parameters: one mainly driven by pruritus scores (chronic kidney disease-associated pruritus cluster), one by mental health scores (mental health cluster) and one by inflammatory parameters (inflammatory cluster). Factor analysis showed strong associations (mental health cluster/chronic kidney disease-associated pruritus cluster, r=-0.49; mental health cluster/inflammatory cluster, r=-0.52; inflammatory cluster/chronic kidney disease-associated pruritus cluster, r=0.48). For the first time, complete correlations between inflammation, mental health and pruritus in dialysis patients have been established. As all 3 conditions are associated with mortality, knowledge about their interdependence helps to understand end-stage renal disease pathophysiology.

Prevalence of chronic kidney disease-associated pruritus, and association with sleep quality among hemodialysis patients in Pakistan.

BackgroundThe prevalence of chronic kidney disease-associated pruritus (CKD-aP) varies from 22% to 84% among patients receiving hemodialysis. It occurs more frequently at night, and often affects patient’s sleep quality. CKD-aP is often unreported by patients, and many do not receive effective treatment. There is, however, a paucity of available data on the prevalence and impact of CKD-aP on patients receiving hemodialysis in Pakistan.MethodsA multicenter cross-sectional study was undertaken from July 2016 to April 2017 at a tertiary care hospitals in Pakistan.Results354 patients undergoing hemodialysis were studied. 35.6% had CKD for 1–2 years, and 42.4% were receiving hemodialysis for 1–2 years. The prevalence of pruritus was 74%. The median [interquartile range] score for pruritus was 10.0 (out of possible 25) [8.0–12.0]; while the median [interquartile range] Pittsburgh Sleep Quality Index (PSQI) score was 8.0 (out of possible 21) [7.0–10.0]'. Pruritus was significantly correlated with the sleep score (r = 0.423, p<0.001). The results of the multivariate linear regression revealed a positive association between pruritus and age of patients (β = 0.031; 95% CI = 0.002–0.061; p = 0.038) and duration of CKD (β = -0.013; 95% CI = -0.023 –-0.003; p = 0.014). Similarly there was a positive association between sleep score and duration of CKD (β = 0.010; 95% CI = 0.002–0.019; p = 0.012) and pruritus (β = 0.143; 95% CI = 0.056–0.230; p = 0.001).ConclusionsChronic kidney disease-associated pruritus is very common in patients receiving hemodialysis in Pakistan. Pruritus is significantly associated with poor sleep quality.

A randomized controlled trial for effectiveness of zolpidem versus acupressure on sleep in hemodialysis patients having chronic kidney disease-associated pruritus: Erratum.

A randomized controlled trial for effectiveness of zolpidem versus acupressure on sleep in hemodialysis patients having chronic kidney disease-associated pruritus: Erratum.