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).

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.

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.

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.

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.

Vascular access for intensive maintenance hemodialysis: a systematic review for a Canadian Society of Nephrology clinical practice guideline.

BACKGROUND: Practices in vascular access management with intensive hemodialysis may differ from those used in conventional hemodialysis. STUDY DESIGN: We conducted a systematic review to inform clinical practice guidelines for the provision of intensive hemodialysis. SETTING & POPULATION: Adult patients receiving maintenance (>3 months) intensive hemodialysis (frequent [≥5 hemodialysis treatments per week] and/or long [>5.5 hours per hemodialysis treatment]). SELECTION CRITERIA FOR STUDIES: We searched EMBASE and MEDLINE (1990-2011) for randomized and observational studies. We also searched conference proceedings (2007-2011). INTERVENTIONS: (1) Central venous catheter (CVC) versus arteriovenous (AV) access, (2) buttonhole versus rope-ladder cannulation, (3) topical antimicrobial cream versus none in buttonhole cannulation, and (4) closed connector devices among CVC users. OUTCOMES: Access-related infection, survival, hospitalization, patency, access survival, intervention rates, and quality of life. RESULTS: We included 23, 7, and 5 reports describing effectiveness by access type, buttonhole cannulation, and closed connector device, respectively. No study directly compared CVC with AV access. On average, bacteremia and local infection rates were higher with CVC compared with AV access. Access intervention rates were higher with more frequent hemodialysis, but access survival did not differ. Buttonhole cannulation was associated with bacteremia rates similar to those seen with CVCs in some series. Topical mupirocin seemed to attenuate this effect. No direct comparisons of closed connector devices versus standard luer-locking devices were found. Low rates of actual or averted (near misses) air embolism and bleeding were reported with closed connector devices. LIMITATIONS: Overall, evidence quality was very low. Limited direct comparisons addressing main review questions, small sample sizes, selective outcome reporting, publication bias, and residual confounding were major factors. CONCLUSIONS: This review highlights several differences in the management of vascular access in conventional and intensive hemodialysis populations. We identify a need for standardization of vascular access outcome reporting and a number of priorities for future research.

Dialysate calcium concentration and mineral metabolism in long and long-frequent hemodialysis: a systematic review and meta-analysis for a Canadian Society of Nephrology clinical practice guideline.

BACKGROUND: Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. STUDY DESIGN: Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. SETTING & POPULATION: Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. SELECTION CRITERIA FOR STUDIES: We included clinical trials, cohort studies, case series, case reports, and systematic reviews. INTERVENTIONS: Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. OUTCOMES: Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. RESULTS: 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. LIMITATIONS: Almost all the available information is related to changes in laboratory values and surrogate outcomes. CONCLUSIONS: Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.

Canadian Society of Nephrology guidelines for the management of patients with ESRD treated with intensive hemodialysis.

Intensive (longer and more frequent) hemodialysis has emerged as an alternative to conventional hemodialysis for the treatment of patients with end-stage renal disease. However, given the differences in dialysis delivery and models of care associated with intensive dialysis, alternative approaches to patient management may be required. The purpose of this work was to develop a clinical practice guideline for the Canadian Society of Nephrology. We applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for guideline development and performed targeted systematic reviews and meta-analysis (when appropriate) to address prioritized clinical management questions. We included studies addressing the treatment of patients with end-stage renal disease with short daily (≥5 days per week, <3 hours per session), long (3-4 days per week, ≥5.5 hours per session), or long-frequent (≥5 days per week, ≥5.5 hours per session) hemodialysis. We included clinical trials and observational studies with or without a control arm (1990 and later). Based on a prioritization exercise, 6 interventions of interest included optimal vascular access type, buttonhole cannulation, antimicrobial prophylaxis for buttonhole cannulation, closed connector devices, and dialysate calcium and dialysate phosphate additives for patients receiving intensive hemodialysis. We developed 6 recommendations addressing the interventions of interest. Overall quality of the evidence was very low and all recommendations were conditional. We provide detailed commentaries to guide in shared decision making. The main limitation was the very low overall quality of evidence that precluded strong recommendations. Most included studies were small single-arm observational studies. Three randomized controlled trials were applicable, but provided only indirect evidence. Published information for patient values and preference was lacking. In conclusion, we provide 6 recommendations for the practice of intensive hemodialysis. However, due to very low-quality evidence, all recommendations were conditional. We therefore also highlight priorities for future research.

Identification and management of patients at elevated cardiometabolic risk in canadian primary care: how well are we doing?

BACKGROUND: We evaluated the risk assessment and management patterns employed by primary care physicians in patients at elevated cardiometabolic risk. METHODS: Between April 2011 and March 2012, multiple physicians from 9 Primary Care Teams (PCTs) and 88 physicians from traditional nonteam (Solo) practices completed a practice assessment on the management of 2461 patients > 40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least 1 of the following: dyslipidemia, type 2 diabetes mellitus (T2DM), or hypertension. RESULTS: Individuals with dyslipidemia, T2DM, or hypertension tended to have a body mass index ≥ 25 kg/m(2). Waist circumference measurements, obtained for only 392/829 (47.0%) Solo patients, revealed that 88.9% of these individuals were abdominally obese and that at least 52.2% of Solo patients had metabolic syndrome. Cardiovascular risk, determined by the physicians for 83.5% of all patients without T2DM and typically performed using traditional risk engines, was often miscalculated (43.2% PCTs, 58.8% Solo; P = 0.0007). Healthy behavioural modifications were infrequently recommended (< 50%). Pharmacotherapy was widely used (> 70%) but treatment targets were infrequently met. The composite outcome of guideline-recommended low-density lipoprotein cholesterol, glycemic, and blood pressure targets was met by 9.0% and 8.1% of patients managed by PCT and Solo physicians respectively. CONCLUSIONS: Obesity and cardiovascular risk were underassessed and the latter often underestimated. Patients were infrequently counselled on the benefits of healthy behavioural changes. A paradigm change in assessing and managing obesity and cardiovascular risk via aggressive lifestyle interventions is warranted in individuals at elevated cardiometabolic risk.

Factors associated with suboptimal initiation of dialysis despite early nephrologist referral.

BACKGROUND: STARRT recently demonstrated that many patients experience suboptimal dialysis starts (defined as initiation as an inpatient and/or with a central venous catheter), even when followed by a nephrologist for >12 months (NDT 2011). However, STARRT did not identify the factors associated with suboptimal initiation of dialysis. The objectives of this study were to extend the results of STARRT by ascertaining the factors leading to suboptimal initiation of dialysis in patients who were referred at least 12 months prior to commencement of dialysis. METHODS: At each of the three Toronto centers, charts of consecutive incident RRT patients were identified from 1 January 2009 to 31 December 2010, with predetermined data extracted. RESULTS: A total of 436 incident RRT patients were studied; 52.4% were followed by a nephrologist for >12 months prior to the initiation of dialysis. Suboptimal starts occurred in 56.4% of these patients. No attempt at arteriovenous fistula (AVF) or arteriovenous graft (AVG) prior to initiation was made in 65% of these starts. Factors contributing to suboptimal starts despite early referral included patient-related delays (31.25%), acute-on-chronic kidney disease (31.25%), surgical delays (16.41%), late decision-making (8.59%) and others (12.50%). The percentage of optimal starts with early referral among 14 nephrologists ranged from 33 to 72%. CONCLUSIONS: Most patients started dialysis in a suboptimal manner, despite an extended period of pre-dialysis care. Nephrologists should take responsibility for suboptimal initiation of dialysis despite early referral and test methods that attempt to prevent this.

Cost-effectiveness analysis of therapies for chronic kidney disease patients on dialysis: a case for excluding dialysis costs.

In many jurisdictions, cost-effectiveness analysis (CEA) plays an important role in determining drug coverage and reimbursement and, therefore, has the potential to impact patient access. Health economic guidelines recommend the inclusion of future costs related to the intervention of interest within CEAs but provide little guidance regarding the definition of 'related'. In the case of CEAs of therapies that extend the lives of patients with chronic kidney disease (CKD) on dialysis but do not impact the need for or the intensity of dialysis, the determination of the relatedness of future dialysis costs to the therapy of interest is particularly ambiguous. The uncertainty as to whether dialysis costs are related or unrelated in these circumstances has led to inconsistencies in the conduct of CEAs for such products, with dialysis costs included in some analyses while excluded in others. Due to the magnitude of the cost of dialysis, whether or not dialysis costs are included in CEAs of such therapies has substantial implications for the results of such analyses, often meaning the difference between a therapy being deemed cost effective (in instances where dialysis costs are excluded) or not cost effective (in instances where dialysis costs are included). This paper explores the issues and implications surrounding the inclusion of dialysis costs in CEAs of therapies that extend the lives of dialysis patients but do not impact the need for dialysis. Relevant case studies clearly demonstrate that, regardless of the clinical benefits of a life-extending intervention for dialysis patients, and due to the high cost of dialysis, the inclusion of dialysis costs in the analysis essentially eliminates the possibility of obtaining a favourable cost-effectiveness ratio. This raises the significant risk that dialysis patients may be denied access to interventions that are cost effective in other populations due solely to the high background cost of dialysis itself. Finally, the paper presents a case for excluding dialysis costs in CEAs of therapies that extend the lives of patients receiving dialysis but do not impact the need for dialysis. The argument is founded on the following: (i) health economic guidelines imply that dialysis costs are unrelated to such therapies and therefore should not be included in CEAs of such therapies; (ii) the high cost and cost-effectiveness ratio associated with dialysis place an unreasonable and insurmountable barrier to demonstrating the cost effectiveness of such therapies, particularly since the decision to fund dialysis has already been made; and (iii) current clinical and reimbursement practices include the use of such therapies for patients with CKD receiving dialysis. We conclude that the exclusion of dialysis costs in such cases is methodologically correct given current health economic guidelines and is consistent with current practices regarding the treatment of dialysis patients.

Intensive hemodialysis associates with improved survival compared with conventional hemodialysis.

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Regression of left ventricular mass following conversion from conventional hemodialysis to thrice weekly in-centre nocturnal hemodialysis.

BACKGROUND: Increased left ventricular mass (LVM) is associated with adverse outcomes in patients receiving chronic hemodialysis. Among patients receiving conventional hemodialysis (CHD, 3×/week, 4 hrs/session), we evaluated whether dialysis intensification with in-centre nocturnal hemodialysis (INHD, 3×/week, 7-8 hrs/session in the dialysis unit) was associated with regression of LVM. METHODS: We conducted a retrospective cohort study of CHD recipients who converted to INHD and received INHD for at least 6 months. LVM on the first echocardiogram performed at least 6 months post-conversion was compared to LVM pre-conversion. In a secondary analysis, we examined echocardiograms performed at least 12 months after starting INHD. The effect of conversion to INHD on LVM over time was also evaluated using a longitudinal analysis that incorporated all LVM data on patients with 2 or more echocardiograms. RESULTS: Thirty-seven patients were eligible for the primary analysis. Mean age at conversion was 49 ± 12 yrs and 30% were women. Mean pre-conversion LVM was 219 ± 66 g and following conversion, LVM declined by 32 ± 58 g (p = 0.002). Among patients whose follow-up echocardiogram occurred at least 12 months following conversion, LVM declined by 40 ± 56 g (p = 0.0004). The rate of change of LVM decreased significantly from 0.4 g/yr before conversion, to -11.7 g/yr following conversion to INHD (p < 0.0001). CONCLUSION: Conversion to INHD is associated with a significant regression in LVM, which may portend a more favourable cardiovascular outcome. Our preliminary findings support the need for randomized controlled trials to definitively evaluate the cardiovascular effects of INHD.

Cardiometabolic risk in Canada: a detailed analysis and position paper by the cardiometabolic risk working group.

The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations.

Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary).

With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations.

Nocturnal hemodialysis: effects on solute clearance, quality of life, and patient survival.

PURPOSE OF REVIEW: Conventional hemodialysis is often an incomplete treatment for uremia. People receiving hemodialysis often report a poor quality of life and suffer from an accelerated mortality rate. Nocturnal hemodialysis provides long treatments at night in the home or dialysis center. This review will examine how long nocturnal treatments have impact on the clearance of small and larger retention products, and how these treatments influence quality of life and survival. RECENT FINDINGS: Nocturnal hemodialysis is more effective at clearing most small and middle molecule retention products, and has been associated with improvements in quality of life, especially in those domains related to the effects of kidney disease. Survival on nocturnal hemodialysis is higher than expected, and studies suggest that patients receiving nocturnal hemodialysis have a mortality rate that is about one third of what is seen in similar patients receiving conventional hemodialysis. SUMMARY: Although impressive, it is difficult to be sure how much of the results of these studies is due to the duration and timing of dialysis and how much relates to patient level factors and residual confounding, and further research in this area is required.