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.

Management of Type 2 Diabetic Kidney Disease in 2022: A Narrative Review for Specialists and Primary Care.

Purpose of review: Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. Sources of information: An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Methods: Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. Key findings: It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients' needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors and/or finerenone is an important component of treatment. Limitations: No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines.

Justification: L'insuffisance rénale est présente chez près de la moitié des patients canadiens atteints de diabète de type 2 (DT2). Il s'agit également de la première manifestation cardiorénale la plus fréquente du DT2. Bien qu'il existe des lignes directrices claires pour son dépistage, des occasions de diagnostiquer l'insuffisance rénale sont manquées, ce qui fait en sorte que de nombreux Canadiens ne reçoivent pas les meilleurs traitements disponibles. Cette préoccupation a pris de l'importance puisque de récents essais cliniques ont démontré des améliorations dans les paramètres rénaux et cardiovasculaires (CV) avec la prise de finérénone, un antagoniste non stéroïdien des récepteurs minéralocorticoïdes (nsMRA), et d'inhibiteurs du cotransporteur de glucose de sodium 2 (SGLT2). L'objectif de cet article est de fournir une revue narrative des données probantes actuelles appuyant cette nouvelle norme de soins pour le traitement de l'insuffisance rénale diabétique (IRD), ainsi que des points de pratique. Sources de l'information: Un groupe d'experts composé de cliniciens canadiens, dont neuf néphrologues, un endocrinologue et un prestataire de soins primaires, a été formé. Les auteurs de cette revue ont utilisé des lignes directrices et des essais cliniques publiés comme sources; ceux-ci ont été choisis sur la base d'une évaluation de leur pertinence pour les questions auxquelles ils avaient répondu. Méthodologie: Les panélistes se sont réunis virtuellement pour discuter de potentielles questions à répondre dans le cadre de cette revue, et se sont entendus sur dix questions clés. Deux membres du panel se sont portés volontaires pour être co-responsables et rédiger les résumés et les points de pratique pour chacune des questions identifiées. Ces derniers ont été distribués par courriel à l'ensemble des auteurs. Après deux tours de vote en ligne, une deuxième réunion virtuelle et la correspondance électronique qui a suivi, les auteurs sont parvenus à un consensus sur le contenu de la revue narrative, y compris sur tous les points de pratique. Principaux résultats: Il est essentiel que l'IRD soit diagnostiquée le plus tôt possible afin de prévenir de façon optimale la progression de la maladie et les complications qui y sont associées. On devrait procéder au dépistage systématique de l'IRD chez les patients diabétiques par l'évaluation de l'albumine urinaire ET de la fonction rénale. Les décisions relatives au traitement devraient être individualisées en fonction des risques et des avantages pour le patient, de ses besoins et préférences, de l'accès aux médicaments et des coûts, ainsi que du degré nécessaire de réduction de la glycémie. Les patients atteints d'IRD devraient être traités pour atteindre les cibles d'A1c et de pression artérielle. Le blocage du SRAA et le traitement avec des inhibiteurs du SGLT2 sont également des composantes clés de la norme de soins visant à réduire le risque d'événements rénaux et CV pour ces patients. La finérénone devrait également être envisagée pour réduire encore davantage les risques d'événements CV et de progression vers l'IRC. L'éducation des patients diabétiques auxquels on prescrit des inhibiteurs du SGLT2 et/ou de la finérénone est un élément important du traitement. Limites: Aucun processus officiel de directives n'a été utilisé. Les points de pratique ne sont pas notés et ne sont pas destinés à être considérés comme ayant le poids d'une directive de pratique clinique ou d'une déclaration de consensus officielle. Cependant, la plupart des points de pratique sont bien alignés avec les lignes directrices actuelles de pratique clinique.

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review.

PURPOSE OF REVIEW: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli-induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. SOURCES OF INFORMATION: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted with PubMed or based on the prior knowledge of the authors. METHODS: This review is the result of a consultation process that reflects the consensus of experts from Canada, the United States, and the United Arab Emirates. The members represent individuals who are clinicians, researchers, and teachers in pediatric and adult medicine from the fields of hematology, nephrology, and laboratory medicine. Authors, through an iterative review process identified and synthesized information from relevant published studies. KEY FINDINGS: Thrombotic thrombocytopenic purpura occurs in the setting of insufficient activity of the von Willebrand factor protease known as ADAMTS13. Shiga toxin-producing Escherichia coli-induced hemolytic uremic syndrome, also known as "typical" HUS, is caused by gastrointestinal infections with bacteria that produce Shiga toxin (initially called verocytotoxin). A variety of clinical conditions or drug exposures can trigger TMA. Finally, aHUS occurs in the setting of inherited or acquired abnormalities in the alternative complement pathway leading to dysregulated complement activation, often following a triggering event such as an infection. It is possible to break the process of etiological diagnosis of TMA into 2 distinct steps. The first covers the initial presentation and diagnostic workup, including the processes of identifying the presence of TMA, appropriate initial tests and referrals, and empiric treatments when appropriate. The second step involves confirming the etiological diagnosis and moving to definitive treatment. For many forms of TMA, the ultimate response to therapies and the outcome of the patient depends on the rapid and accurate identification of the presence of TMA and then a standardized approach to seeking the etiological diagnosis. We present a structured approach to identifying the presence of TMA and steps to identifying the etiology including standardized lab panels. We emphasize the importance of early consultation with appropriate specialists in hematology and nephrology, as well as identification of whether the patient requires plasma exchange. Clinicians should consider appropriate empiric therapies while following the steps we have recommended toward definitive etiologic diagnosis and management of the TMA. LIMITATIONS: The evidence base for our recommendations consists of small clinical studies, case reports, and case series. They are generally not controlled or randomized and do not lend themselves to a stricter guideline-based methodology or a Grading of Recommendations Assessment, Development and Evaluation (GRADE)-based approach.

JUSTIFICATION: La microangiopathie thrombotique (MAT) est suspectée chez les patients présentant une thrombocytopénie et la preuve d'une anémie hémolytique microangiopathique (AHMA). Les patients atteints de MAT peuvent être gravement malades, il est donc essentiel de déterminer rapidement et précisément l'étiologie sous-jacente. Grâce à une meilleure connaissance de la physiopathologie et des causes de la MAT, nous pouvons désormais classer les MAT par catégorie: purpura thrombocytopénique thrombotique (PTT), syndrome hémolytique urémique post-infectieux (SHU) principalement induit par STEC (Escherichia coli produisant la toxine Shiga), ou MAT associée à une affection coexistante ou à un SHU atypique (SHUa). Nous avons constaté un besoin dans la communauté médicale pour guider à la fois la détection rapide et précise de la MAT, la sélection des tests pour clarifier son étiologie et la séquence des étapes menant à l'initiation du traitement. SOURCES: Des recherches documentaires sur PubMed et les connaissances antérieures des auteurs ont permis de colliger les principales études publiées portant sur la détection, la classification et le traitement de la MAT chez les enfants ou les adultes. MÉTHODOLOGIE: Cet examen est le résultat d'un processus de consultation qui reflète le consensus des experts du Canada, des États-Unis et des Émirats arabes Unis. Les membres représentent des cliniciens, des chercheurs et des enseignants en médecine pédiatrique et adulte dans les domaines de l'hématologie, de la néphrologie et de la médecine de laboratoire. Les auteurs, par le biais d'un processus d'examen itératif, ont colligé et synthétisé l'information provenant des études publiées jugées pertinentes. PRINCIPAUX RÉSULTATS: Le PTT survient lors d'une activité insuffisante de la protéase du facteur Willebrand connue sous le nom d'ADAMTS13. Le SHU-STEC, aussi appelé SHU « typique ¼, est causé par des infections gastro-intestinales dues à des bactéries produisant la toxine Shiga (initialement appelée vérocytotoxine). Plusieurs états pathologiques ou expositions à des médicaments peuvent déclencher la MAT. Quant au SHU atypique (SHUa), il survient en présence d'anomalies héréditaires ou acquises de la voie du complément alternatif qui mènent à un dérèglement de l'activation du complément, souvent à la suite d'un événement déclencheur comme une infection. On peut diviser le processus de diagnostic étiologique de la MAT en deux étapes distinctes. La première couvre la présentation initiale et le diagnostic, y compris les processus de détection de la MAT, les tests initiaux et aiguillages appropriés, ainsi que les traitements empiriques si nécessaire. La deuxième étape consiste à confirmer le diagnostic étiologique et à procéder au traitement définitif. Pour de nombreuses formes de MAT, la réponse ultime aux traitements et le résultat du patient dépendent de la détection rapide et précise de la MAT et ensuite, d'une approche standardisée pour la recherche du diagnostic étiologique. Nous présentons une approche structurée pour détecter la présence de MAT ainsi qu'une démarche pour rechercher l'étiologie, y compris des tableaux de laboratoire normalisés. Nous soulignons l'importance d'une consultation précoce avec les spécialistes appropriés en hématologie et en néphrologie, et de la détermination d'un éventuel besoin d'échange de plasma (PLEX) pour le patient. Les cliniciens devraient envisager les traitements empiriques appropriés tout en suivant la démarche que nous recommandons pour le diagnostic étiologique définitif et la gestion de la MAT. LIMITES: La base factuelle de nos recommandations est constituée de petites études cliniques, de rapports de cas et de séries de cas. Ces études ne sont généralement pas contrôlées ou randomisées et ne se prêtent pas à une méthodologie plus stricte basée sur des lignes directrices ni à une approche fondée sur le GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Update to Evidence-Based Secondary Prevention Strategies After Acute Coronary Syndrome.

A recent acute coronary syndrome provides an opportunity to optimise secondary prevention strategies to reduce the risk of future cardiovascular events. This review provides an updated synopsis of current evidence-based approaches. New clinical trial data on the use of antiplatelet and anticoagulants allow choices of the selection and duration of treatment. Lipid lowering after an acute coronary syndrome is now enhanced, with proprotein convertase subtilisin-kexin type 9 inhibitors providing added benefit on top of statin and ezetimibe treatment in high-risk patients. In addition, a recent trial of icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, addresses residual risk in patients with elevated triglycerides already treated with statins. The use of both sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes reduces cardiovascular events independently of glucose lowering.

La survenue récente d'un syndrome coronarien aigu offre l'occasion d'optimiser les stratégies de prévention secondaire en vue de réduire le risque d'événements cardiovasculaires futurs. Le présent article de synthèse offre une vue d'ensemble actualisée des approches contemporaines fondées sur des données probantes. Les nouvelles données d'essais cliniques sur l'utilisation d'antiplaquettaires et d'anticoagulants permettent de choisir un traitement et sa durée. La réduction des lipides après la survenue d'un syndrome coronarien aigu se trouve maintenant améliorée, les bienfaits des inhibiteurs de la proprotéine convertase subtilisine/kexine de type 9 s'ajoutant à ceux du traitement par des statines et l'ézétimibe chez les patients à haut risque. En outre, un essai récent portant sur l'icosapent éthyl, un ester éthylique hautement purifié de l'acide eicosapentaénoïque, aborde le risque résiduel chez les patients présentant une hypertriglycéridémie déjà traités par des statines. L'utilisation d'inhibiteurs du cotransporteur sodium-glucose de type 2 et d'agonistes des récepteurs du peptide-1 apparenté au glucagon chez les patients atteints de diabète de type 2 limite les événements cardiovasculaires indépendamment de la diminution de la glycémie.

A Peritoneal Dialysis Access Quality Improvement Initiative: A Single-Center Experience.

Background:Little evidence exists regarding optimal peritoneal dialysis (PD) access insertion pathways, benchmarking for patency targets, and definitions of access dysfunction.Methods:This quality improvement (QI) project evaluated patients with PD catheters inserted at a single center in Toronto, Canada, following: establishment of PD catheter insertion protocols, a PD access coordinator, PD access operator training, and outcomes reporting. We define primary vs secondary PD catheter dysfunction by presentation before/after initial home PD treatment. We report catheter dysfunction rates, interventions restoring PD catheter patency (interventional radiology [IR] vs advanced laparoscopic [AL]) (embedded vs non-embedded) between 2012 and 2017.Results:A total of 297 first PD catheters were inserted between January 2012 and December 2017. Interventional radiology PD catheters (n = 94) were placed in older patients with greater comorbidities and less prior abdominal surgery than AL-placed catheters. Indications for IR insertion included need for urgent dialysis given resource availability (36.2% [n = 34]) and prohibitive surgical risk (26.6% [n = 25]). Interventional radiology-inserted catheters had overall (primary and secondary) dysfunction rates of 17%. Non-embedded AL catheters had 16.1% overall dysfunction. Embedded AL-inserted PD catheters had a 24.6% overall dysfunction rate. Among all dysfunctional catheters, IR manipulation was successful in 31% (n = 11), and surgical revision was necessary in all unsuccessful cases with either lysis of adhesions or omentopexy to establish patency.Conclusion:Our PD catheter QI initiative involved tracking, outcome reporting, defining PD catheter dysfunction and PD access insertion pathway development, yielding important insights into opportunities for program improvement. Multicenter research initiatives are needed to further improve PD access dysfunction definitions and to establish the best benchmarks for these metrics.

The role of sodium glucose cotransporter-2 (SGLT-2) inhibitors in heart failure and chronic kidney disease in type 2 diabetes.

Background: Heart failure (HF) and chronic kidney disease (CKD) are responsible for substantial morbidity and mortality in individuals with type 2 diabetes (T2D). Methods: This review discusses the significance of these comorbidities of T2D and current options for managing them, with a focus on sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Based on a focused literature search of cardiovascular outcomes trials (CVOTs), this review assessed the effects of SGLT-2 inhibitors in individuals with T2D with or without established cardiovascular disease (CVD). Results: In addition to effective glycemic control and weight loss, SGLT-2 inhibitor treatment of T2D prevents adverse cardiovascular and renal outcomes in individuals with and without these comorbidities. Reduced rate of hospitalization due to HF (HHF) and improved renal outcomes appear to be class effects of SGLT-2 inhibitors. Reduction in CV events may be more significant in individuals with established cardiovascular disease. Conclusions: CVOTs and other studies confirm that the SGLT-2 inhibitors, mostly used in combination with other glucose-lowering drugs, offer several clinical benefits beyond improved glycemic control. These include reducing HHF risk and improving renal outcomes. HF and renal benefits are observed in individuals with and without established CVD, which may simplify therapeutic selection. Ongoing SGLT-2 inhibitor CVOTs will help clarify the potential of these drugs to treat T2D comorbid with different forms of HF (HF with preserved vs reduced ejection fraction) and different degrees of renal dysfunction, and in individuals with T2D vs pre-diabetes or normal glucose metabolism.

Buttonhole versus Stepladder Cannulation for Home Hemodialysis: A Multicenter, Randomized, Pilot Trial.

BACKGROUND AND OBJECTIVES: Canadian home hemodialysis guidelines highlight the potential differences in complications associated with arteriovenous fistula (AVF) cannulation technique as a research priority. Our primary objective was to determine the feasibility of randomizing patients with ESKD training for home hemodialysis to buttonhole versus stepladder cannulation of the AVF. Secondary objectives included training time, pain with needling, complications, and cost by cannulation technique. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients training for home hemodialysis at seven Canadian hospitals were assessed for eligibility, and demographic information and access type was collected on everyone. Patients who consented to participate were randomized to buttonhole or stepladder cannulation technique. Time to train for home hemodialysis, pain scores on cannulation, and complications over 12 months was recorded. For eligible but not randomized patients, reasons for not participating in the trial were documented. RESULTS: Patient recruitment was November 2013 to November 2015. During this time, 158 patients began training for home hemodialysis, and 108 were ineligible for the trial. Diabetes mellitus as a cause of ESKD (31% versus 12%) and central venous catheter use (74% versus 6%) were more common in ineligible patients. Of the 50 eligible patients, 14 patients from four out of seven sites consented to participate in the study (28%). The most common reason for declining to participate was a strong preference for a particular cannulation technique (33%). Patients randomized to buttonhole versus stepladder cannulation required a shorter time to complete home hemodialysis training. We did not observe a reduction in cannulation pain or complications with the buttonhole method. Data linkages for a formal cost analysis were not conducted. CONCLUSIONS: We were unable to demonstrate the feasibility of conducting a randomized, controlled trial of buttonhole versus stepladder cannulation in Canada with a sufficient number of patients on home hemodialysis to be able to draw meaningful conclusions.

Updated Canadian Expert Consensus on Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease.

PURPOSE: The purpose of this article is to update the previously published consensus recommendations from March 2017 discussing the optimal management of adult patients with autosomal dominant polycystic kidney disease (ADPKD). This document focuses on recent developments in genetic testing, renal imaging, assessment of risk regarding disease progression, and pharmacological treatment options for ADPKD. SOURCES OF INFORMATION: Published literature was searched in PubMed, the Cochrane Library, and Google Scholar to identify the latest evidence related to the treatment and management of ADPKD. METHODS: All pertinent articles were reviewed by the authors to determine if a new recommendation was required, or if the previous recommendation needed updating. The consensus recommendations were developed by the authors based on discussion and review of the evidence. KEY FINDINGS: The genetics of ADPKD are becoming more complex with the identification of new and rarer genetic variants such as GANAB. Magnetic resonance imaging (MRI) and computed tomography (CT) continue to be the main imaging modalities used to evaluate ADPKD. Total kidney volume (TKV) continues to be the most validated and most used measure to assess disease progression. Since the publication of the previous consensus recommendations, the use of the Mayo Clinic Classification for prognostication purposes has been validated in patients with class 1 ADPKD. Recent evidence supports the benefits of a low-osmolar diet and dietary sodium restriction in patients with ADPKD. Evidence from the Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial supports the use of ADH (antidiuretic hormone) receptor antagonism in patients with ADPKD 18 to 55 years of age with eGFR (estimated glomerular filtration rate) of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year. LIMITATIONS: Available literature was limited to English language publications and to publications indexed in PubMed, the Cochrane Library, and Google Scholar. IMPLICATIONS: Advances in the assessment of the risk of disease progression include the validation of the Mayo Clinic Classification for patients with class 1 ADPKD. Advances in the pharmacological management of ADPKD include the expansion of the use of ADH receptor antagonism in patients 18 to 55 years of age with eGFR of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year, as per the results of the REPRISE study.

MOTIF: L'objet de cet article est de faire une mise à jour des recommandations consensuelles publiées en mars 2017 traitant de la prise en charge des patients adultes atteints de la maladie polykystique autosomique dominante (MPAD). Ce document s'intéresse aux développements récents en matière de dépistage génétique, d'imagerie rénale, d'évaluation des risques de progression de la maladie et des options de traitement pharmacologique de la MPAD. SOURCES: Les plus récents développements liés à la prise en charge et au traitement de la MPAD ont été colligés à partir des articles publiés sur le sujet dans PubMed, la bibliothèque Cochrane et Google Scholar. MÉTHODOLOGIE: Les auteurs ont relu tous les articles pertinents pour déterminer si de nouvelles recommandations étaient requises ou si les recommandations ultérieures nécessitaient une mise à jour. Les recommandations consensuelles ont été élaborées par les auteurs à partir de la discussion et de la révision des données probantes. PRINCIPAUX RÉSULTATS: Les caractéristiques génétiques de la MPAD deviennent de plus en plus complexes avec l'identification de nouvelles et de plus rares variantes telles que GANAB. L'IRM et la tomodensitométrie demeurent les principales modalités d'imagerie utilisées pour le diagnostic et l'évaluation de la MPAD. Le volume rénal total (VRT) continue d'être la mesure la mieux validée et la plus employée pour évaluer la progression de la maladie. Depuis la publication des précédentes recommandations consensuelles, le recours à la classification de la Clinique Mayo a été validé à des fins pronostiques chez les patients atteints de MPAD de type 1. Des données récentes soutiennent les bienfaits d'une diète à faible osmolarité et des restrictions alimentaires pour le sodium chez les patients atteints de la MPAD. Les résultats de l'essai REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) viennent appuyer le recours à des antagonistes des récepteurs de l'ADH chez les patients atteints de la MPAD âgés de 18 à 55 ans et dont le DFGe se situe entre 25 et 65 mL/min/1,73 m2 ou chez ceux qui sont âgés de 56 à 65 ans et dont le DFGe se situe entre 25 et 44 mL/min/1,73 m2 et dont les antécédents montrent un déclin du DFGe supérieur à 2,0 mL/min/1,73 m2 par année. LIMITES: La recherche s'est limitée aux publications en anglais et indexées sur PubMed, Google Scholar et dans la bibliothèque Cochrane. IMPLICATIONS: Les avancées dans l'évaluation du risque de progression de la maladie incluent la validation de la classification de la clinique Mayo pour les patients atteints de MPAD de type 1. Les développements dans la prise en charge pharmacologique de la MPAD incluent les résultats obtenus lors de l'essai REPRISE; soit l'élargissement de l'utilisation des antagonistes des récepteurs de l'ADH aux patients âgés de 18 à 25 ans dont le DFGe se situe entre 25 et 65 mL/min/1,73 m2 ou à ceux âgés de 56 à 65 ans dont le DFGe se situe entre 25 et 44 mL/min/1,73 m2 et dont les antécédents montrent un déclin du DFGe supérieur à 2,0 mL/min/1,73 m2 par année.

Resistant Hypertension in Adults With Type 1 or 2 Diabetes: A Structured Diagnostic Approach.

People with diabetes often have difficulty reaching their blood pressure targets and are labelled as having resistant hypertension. Clinicians often move quickly to screen such people for secondary causes of hypertension; however, such causes are rare, and resistant hypertension usually has other explanations that are significantly more common. By using a structured approach to resistant hypertension, clinicians can assist patients to reach their target blood pressure levels. Step 1 is to determine out-of-office blood pressure measurements using home or ambulatory blood pressure monitors. Step 2 is to determine the level of adherence to prescribed medications. Step 3 is to identify interfering substances. Step 4 is to check that the prescribed medications are synergistic and optimally dosed. Finally, if all other steps fail to get patients to their blood pressure targets, we consider possible secondary causes of hypertension. This approach is particularly useful in helping people with diabetes to reach their blood pressure targets.

Managing the Course of Kidney Disease in Adults With Type 2 Diabetes: From the Old to the New.

Diabetic kidney disease (DKD) is a group of chronic kidney diseases that is associated with significant cardiovascular as well as all-cause morbidity and mortality. Although DKD is often progressive in nature, its evolution can be modified by intensive management of glycemia and blood pressure and inhibition of the renin-angiotensin-aldosterone system. This review provides an overview of how multifactorial interventions can provide renal protection and includes a discussion of the nonglycemic effects of incretin-based diabetes therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors) and sodium-glucose cotransporter-2 inhibitors within the kidney in patients with type 2 diabetes.

Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg. For individuals with diastolic hypertension (with or without systolic hypertension), fixed-dose single-pill combinations are now recommended as an initial treatment option. Preference is given to pills containing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in combination with either a calcium channel blocker or diuretic. Whenever a diuretic is selected as monotherapy, longer-acting agents are preferred. In patients with established ischemic heart disease, caution should be exercised in lowering diastolic non-AOBP to ≤ 60 mm Hg, especially in the presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended. Finally, guidance is now provided for screening, initial diagnosis, assessment, and treatment of renovascular hypertension arising from fibromuscular dysplasia. The specific evidence and rationale underlying each of these guidelines are discussed.

Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease: A Canadian Expert Consensus.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD. The purpose of this consensus recommendation is to develop an evidence-informed recommendation for the optimal management of adult patients with ADPKD. This document focuses on the role of genetic testing, the role of renal imaging, predicting the risk of disease progression, and pharmacological treatment options for ADPKD. These areas of focus were derived from 2 national surveys that were disseminated to nephrologists and patients with ADPKD with the aim of identifying unmet needs in the management of ADPKD in Canada. Specific recommendations are provided for the treatment of ADPKD with tolvaptan.

La polykystose rénale autosomique dominante (PKRAD) est le trouble rénal héréditaire le plus fréquent dans le monde. La maladie est caractérisée par la présence de kystes rénaux et par une insuffisance rénale progressive provoquée par l'élargissement progressif des kystes et par une fibrose rénale. Environ 45 à 70% des patients atteints de PKRAD verront leur état évoluer vers l'insuffisance rénale terminale avant l'âge de 65 ans. Bien que les thérapies ciblées et non ciblées aient été testées chez des patients atteints de PKRAD, le tolvaptan est le seul médicament approuvé au Canada pour le traitement de la PKRAD. L'objectif de cette recommandation consensuelle est l'élaboration de recommandations fondées sur des données probantes pour une prise en charge optimale des patients adultes atteints de PKRAD. Ce document met l'accent sur le rôle du dépistage génétique et de l'imagerie rénale, sur les façons de prédire le risque de progression de la maladie et sur les options de traitement pharmacologique de la PKRAD. Ces domaines d'action dérivent de deux enquêtes nationales diffusées aux néphrologues et aux patients canadiens atteints de PKRAD, et qui avaient pour but d'identifier les besoins non satisfaits dans la prise en charge le la PKRAD au Canada. Des recommandations spécifiques sont fournies pour le traitement de la PKD avec le tolvaptan.

Secondary Prevention Beyond Hospital Discharge for Acute Coronary Syndrome: Evidence-Based Recommendations.

In the past 3 decades, a better understanding of the pathophysiology of cardiovascular disease has resulted in innovations in the treatment and prevention of its clinical manifestations such as death, myocardial infarction, or stroke. After an acute coronary syndrome there are short- and long-term risks of subsequent cardiovascular events. This leads to opportunities to initiate strategies to reduce complications resulting from myocardial injury (cardiac protection) and to prevent recurrent acute coronary events (vascular protection). The results from clinical trials inform best practice and guidelines for patient management. Despite clear and consistent guidelines, an important number of patients are not receiving these treatments. Moreover, many others do not receive treatment that follows the strategy proven in the clinical trial and this is associated with a significant loss of opportunities to improve outcomes. The Canadian Heart Research Centre has therefore assembled a panel of experts to provide a review of available data and distill it to specific evidence-based recommendations that can be used by specialists and primary care physicians as a platform for secondary prevention. The therapeutic recommendations are conveniently divided into vascular protection (dual antiplatelet therapy, lipid-lowering, and renin angiotensin system inhibition) which should be considered in all patients; cardiac protection (addition of ß-blocker therapy) in patients with left ventricular dysfunction including consideration for management of heart failure; and continuing management of risk factors and comorbid conditions on the basis of the specific patient profile. These recommendations are intended as a decision support tool and a quick reference for Canadian physicians.

Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a ß-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

Health state utilities associated with major clinical events in the context of secondary hyperparathyroidism and chronic kidney disease requiring dialysis.

BACKGROUND: Patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require dialysis are at increased risk for cardiovascular events and bone fractures. To assist in economic evaluations, this study aimed to estimate the disutility of these events beyond the impact of CKD and SHPT. METHODS: A basic one-year health state was developed describing CKD and SHPT requiring dialysis. Further health states added acute events (cardiovascular events, fractures, and surgical procedures) or chronic post-event effects. Acute health states described a year including an event, and chronic health states described a year subsequent to an event. General population participants in Canada completed time trade-off interviews from which utilities were derived. Pairwise comparisons were made between the basic state and event, and between comparable health states. RESULTS: A total of 199 participants (54.8% female; mean age = 46.3 years) completed interviews. Each health state had ≥130 valuations. The mean (SD) utility of the basic health state was 0.60 (0.34). For acute events, mean utility differences versus the basic state were: myocardial infarction, -0.06; unstable angina, -0.05; peripheral vascular disease (PVD) with amputation, -0.33; PVD without amputation, -0.11; heart failure, -0.14; stroke, -0.30; hip fracture, -0.14; arm fracture, -0.04; parathyroidectomy, +0.02; kidney transplant, +0.06. Disutilities for chronic health states were: stable angina, -0.09; stroke, -0.27; PVD with amputation, -0.30; PVD without amputation, -0.12; heart failure, -0.14. CONCLUSIONS: Cardiovascular events and fractures were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of CKD and SHPT.

Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.

The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

Testing for albuminuria in 2014.

Routine quantification of urinary albumin levels is recommended for all Canadians with diabetes, yet many controversies remain when interpreting these tests. Elevated levels of albuminuria have traditionally been labeled as either microalbuminuria, representing 30 to 300 mg of albuminuria per day (a range not reliably picked up by conventional urine dipsticks), or as overt nephropathy, representing more than 300 mg per day and usually identifiable by dipstick. The random urine albumin-to-creatinine ratio is a convenient test that can predict reliably the total daily protein excretion. The 30 mg per day upper limit of normal was selected to be a threshold far above the normal albumin excretion seen in healthy people. However, recent studies have shown that elevations of albumin excretion below the microalbuminuria threshold are associated with increased cardiorenal risk, suggesting that the 30 mg per day level may be set too high. Recently, the Canadian Diabetes Association Clinical Practice Guidelines changed the threshold for abnormal urine albumin-to-creatinine ratios to be 2.0 mg/mmol for both men and women. As a result, more women will be identified as having abnormal levels of albuminuria. However, these women will be correctly identified as having increased cardiorenal risk. It is important to note that people with diabetes who have abnormal levels of albuminuria are among patients at the highest risk for cardiorenal disease. These risks can be reduced by using the strategies outlined in the guidelines put forth by the Canadian Diabetes Association.

The cost-effectiveness of contemporary home haemodialysis modalities compared with facility haemodialysis: a systematic review of full economic evaluations.

AIM: The financial burden of the increasing dialysis population challenges healthcare resources internationally. Home haemodialysis offers many benefits over conventional facility dialysis including superior clinical, patient-centred outcomes and reduced cost. This review updates a previous review, conducted a decade prior, incorporating contemporary home dialysis techniques of frequent and nocturnal dialysis. We sought comparative cost-effectiveness studies of home versus facility haemodialysis (HD) for people with end-stage kidney failure (ESKF). METHODS: We conducted a systematic review of literature from January 2000-March 2014. Studies were included if they provided comparative information on the costs, health outcomes and cost-effectiveness ratios of home HD and facility HD. We searched medical and health economic databases using MeSH headings and text words for economic evaluation and haemodialysis. RESULTS: Six studies of economic evaluations that compared home to facility HD were identified. Two studies compared home nocturnal HD, one home nocturnal and daily home HD, and three compared contemporary home HD to facility HD. Overall these studies suggest that contemporary home HD modalities are less costly and more effective than facility HD. Home HD start-up costs tend to be higher in the short term, but these are offset by cost savings over the longer term. CONCLUSIONS: Contemporaneous dialysis modalities including nocturnal and daily home haemodialysis are cost-effective or cost-saving compared with facility-based haemodialysis. This result is largely driven by lower staff costs, and better health outcomes for survival and quality of life. Expanding the proportion of haemodialysis patients managed at home is likely to produce cost savings.