Pathways for Diagnosing and Treating CKD-Associated Pruritus: A Narrative Review.

Purpose of Review: Chronic kidney disease (CKD)-associated pruritus is a common, persistent, and distressing itch experienced by patients across the CKD spectrum. Although the disorder is associated with adverse outcomes and poor health-related quality of life, it remains underdiagnosed and undertreated. The purpose of this narrative review is to offer health care providers guidance on how to effectively identify, assess, and treat patients with CKD-associated pruritus, with the goal of reducing symptom burden and improving patient-important outcomes, such as quality of life (QoL). Sources of Information: A panel of nephrologists and researchers from across Canada and the United States was assembled to develop this narrative review based on the best available data, current treatment guidelines, and their clinical experiences. Methods: A panel of nephrologists who actively care for patients with pruritus receiving dialysis from across Canada was assembled. Two researchers from the United States were also included based on their expertise in the diagnosis and management of CKD-associated pruritus. Throughout Spring 2023, the panel met to discuss key topics in the identification, assessment, and management of CKD-associated pruritus. Panel members subsequently developed summaries of the pertinent information based on the best available data, current treatment guidelines, and added information on their own clinical experiences. In all cases, approval of the article was sought and achieved through discussion. Key Findings: This narrative review provides pragmatic guidance addressing: (1) methods for screening CKD-associated pruritus, (2) assessing severity, (3) management of CKD-associated pruritus, and (4) suggested areas for future research. The panel developed a 3-pillar framework for proactive assessment and severity scoring in CKD-aP: systematic screening for CKD-associated pruritus (pillar 1), assessment of pruritus intensity (pillar 2), and understanding the impact of CKD-associated pruritus on the patient's QoL (pillar 3). Management of CKD-associated pruritus can include ensuring optimization of dialysis adequacy, achieving mineral metabolism targets (ie, calcium, phosphate, and parathyroid hormone). However, treatment of CKD-associated pruritus usually requires additional interventions. Patients, regardless of CKD-associated pruritus severity, should be counseled on adequate skin hydration and other non-pharmacological strategies to reduce pruritus. Antihistamines should be avoided in favor of evidence-based treatments, such as difelikefalin and gabapentin. Limitations: A formal systematic review (SR) of the literature was not undertaken, although published SRs were reviewed. The possibility for bias based on the experts' own clinical experiences may have occurred. Key takeaways are based on the current available evidence, of which head-to-head clinical trials are lacking. Funding: This work was funded by an arm's length grant from Otsuka Canada Pharmaceutical Inc. (the importer and distributer of difelikefalin in Canada). LiV Medical Education Agency Inc. provided logistical and editorial support.

Motif de la revue: Le prurit associé à l'insuffisance rénale chronique (IRC) est une démangeaison cutanée fréquente, persistante et invalidante que les patients de tout le specter de l'IRC peuvent ressentir. Bien que le prurit soit associé à des effets indésirables et à une mauvaise qualité de vie liée à la santé, il demeure sous-diagnostiqué et sous-traité. L'objectif de cette revue narrative est d'offrir des conseils aux professionnels de la santé sur la façon d'identifier, d'évaluer et de traiter efficacement les patients atteints de prurit associé à l'IRC; ceci dans le but de réduire la charge des symptômes et d'améliorer les résultats importants pour les patients, notamment leur qualité de vie (QdV). Sources de l'information: Un comité de néphrologues et de chercheurs de partout au Canada et des États-Unis a été constitué pour élaborer la présente revue narrative à partir des meilleures données disponibles, des lignes directrices actuelles pour le traitement et de leurs expériences cliniques. Méthodologie: Un groupe de néphrologues canadiens qui s'occupent activement de patients dialysés souffrant de prurit a été constitué. Deux chercheurs des États-Unis ont été inclus au groupe en raison de leur expertise dans le diagnostic et la prise en charge du prurit associé à l'IRC. Le comité s'est réuni tout au long du printemps 2023 pour discuter de sujets clés en lien avec l'identification, l'évaluation et la prise en charge du prurit associé à l'IRC. Les membres du comité ont par la suite rédigé des résumés des informations pertinentes en se basant sur les meilleures données disponibles et les lignes directrices actuelles pour le traitement, auxquels ils ont ajouté des informations issues de leurs propres expériences cliniques. Dans tous les cas, l'approbation du manuscrit a été sollicitée et obtenue par discussion. Principaux résultats: Cette revue narrative offre des conseils pragmatiques sur les points suivants: (1) les méthodes de dépistage du prurit associé à l'IRC; (2) l'évaluation de sa gravité; (3) sa prise en charge; et (4) les domaines suggérés pour de futures recherches. Le comité a développé un cadre à trois piliers pour l'évaluation proactive du prurit associé à l'IRC et l'établissement d'un score de gravité: le dépistage systématique du prurit associé à l'IRC (pilier 1), l'évaluation de son intensité (pilier 2) et la compréhension de son impact sur la QdV du patient (pilier 3). La prise en charge du prurit associé à l'IRC peut inclure l'optimisation de l'adéquation de la dialyse et l'atteinte des cibles du métabolisme minéral (c.-à-d. calcium, phosphate et hormone parathyroïdienne). Cependant, son traitement nécessite habituellement des interventions supplémentaires. Les patients, quelle que soit la gravité du prurit associé à l'IRC, devraient être avisés d'hydrater adéquatement leur peau et informés des autres stratégies non pharmacologiques afin de réduire le prurit. On devrait éviter les antihistaminiques et les remplacer par des traitements fondés sur des données probantes comme la difélikéfaline et la gabapentine. Limites: Aucune revue systématique de la littérature n'a été formellement entreprise, bien que les revues systématiques publiées aient été examinées. La possibilité d'un biais fondé sur les expériences cliniques des experts est envisageable. Les principales conclusions de cette étude sont fondées sur les données probantes actuellement disponibles, pour lesquelles il n'existe pas d'essais cliniques comparatifs. Financement: Ces travaux ont été financés par une subvention indépendante d'Otsuka Canada Pharmaceutical Inc. (l'importateur et distributeur de la difélikéfaline au Canada). Un soutien logistique et éditorial a été fourni par liV Medical Education Agency Inc.

Guideline attainment and morbidity/mortality rates in a large cohort of European haemodialysis patients (EURODOPPS).

BACKGROUND: Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients. METHODS: EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission. RESULTS: At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission. CONCLUSION: In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality.

[The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study: To better understand chronic kidney disease]. / Cohorte française Chronic Kidney Disease-Réseau Épidémiologie et Information en Néphrologie (CKD-REIN) : mieux connaître la maladie rénale chronique.

BACKGROUND: Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. METHODS: The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. RESULTS: More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. CONCLUSION: The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances.

The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study.

BACKGROUND: While much has been learned about the epidemiology and treatment of end-stage renal disease (ESRD) in the last 30 years, chronic kidney disease (CKD) before the end-stage has been less investigated. Not enough is known about factors associated with CKD progression and complications, as well as its transition to ESRD. We designed the CKD-renal epidemiology and information network (REIN) cohort to provide a research platform to address these key questions and to assess clinical practices and costs in patients with moderate or advanced CKD. METHODS: A total of 46 clinic sites and 4 renal care networks participate in the cohort. A stratified selection of clinic sites yields a sample that represents a diversity of settings, e.g. geographic region, and public versus for-profit and non-for-profit private clinics. In each site, 60-90 patients with CKD are enrolled at a routine clinic visit during a 12-month enrolment phase: 3600 total, including 1800 with Stage 3 and 1800 with Stage 4 CKD. Follow-up will continue for 5 years, including after initiation of renal replacement therapy. Data will be collected from medical records at inclusion and at yearly intervals, as well as from self-administered patient questionnaires and provider-level questionnaires. Patients will also be interviewed at baseline, and at 1, 3 and 5 years. Healthcare costs will also be determined. Blood and urine samples will be collected and stored for future studies on all patients at enrolment and at study end, and at 1 and 3 years in a subsample of 1200. CONCLUSIONS: The CKD-REIN cohort will serve to improve our understanding of the biological, clinical and healthcare system determinants associated with CKD progression and adverse outcomes as well as of international variations in collaboration with the CKD Outcome and Practice Pattern Study (CKDopps). It will foster CKD epidemiology and outcomes research and provide evidence to improve the health and quality of life of patients with CKD and the performances of the healthcare system in this field.

Dialysis Outcomes and Practice Patterns Study estimate of patient life-years attributable to modifiable haemodialysis practices in Sweden.

OBJECTIVE: To examine the association of adherence to Swedish Society of Nephrology guidelines on haemodialysis treatment and patient outcomes in Sweden. MATERIAL AND METHODS: A prevalent cross-sectional sample of Swedish haemodialysis patients was obtained from the Dialysis Outcomes and Practice Patterns Study (DOPPS II, 2002-2004), an international, prospective, cohort study that investigates relationships between patient outcomes and haemodialysis practices. The sample was used to estimate life-years gained through adherence to six potentially modifiable practice patterns: dialysis dose, anaemia, serum phosphorus, serum calcium, serum albumin and catheter use for vascular access. Cox proportional hazards regression models were used to calculate the relative risk of mortality for all patients outside each guideline. RESULTS: The practices resulting in the largest patient-year gains were increasing patient albumin above 35 g/l and reducing facility catheter use to below 10%. Compliance with the albumin target levels could save approximately 441 life-years (or as many as 904 years). Similarly, by 2010, 409 life-years (or as many as 837 years) could be saved if vascular access target levels were achieved. CONCLUSION: The analysis suggests potential opportunities to improve haemodialysis patient care in Sweden. Estimates of life-years saved may serve as motivation for the improvement of patient care through adherence to published guidelines supported by international data from the DOPPS.

Patient selection in the ESRD managed care demonstration.

The Centers for Medicare & Medicaid Service's (CMS') end stage renal disease (ESRD) managed care demonstration offered an opportunity to assess patient selection among a chronically ill and inherently costly population. Patient selection refers to the phenomenon whereby those Medicare beneficiaries who choose to enroll or stay in health maintenance organizations (HMOs) are, on average, younger, healthier, and less costly to treat than beneficiaries who remain in the traditional Medicare fee-for-service (FFS) sector. The results presented in this article show that enrollees into the demonstration were generally younger and healthier than a representative group of comparison patients from the same geographic areas.