Psychosocial Distress in Patients With Advanced CKD by Racial Group and Immigrant Status: A Canadian Cross-sectional Study.

RATIONALE & OBJECTIVE: Patients with advanced chronic kidney disease (CKD) have been reported to experience profound psychosocial distress. Other work has established that patients with CKD from marginalized populations (including individuals who on the basis of race often face racism and related discrimination, termed "racialization") experience health care inequities. Given limited information on the intersection of these 2 phenomena, we assessed the association of psychosocial distress with racialized status and immigrant status in Canadians with advanced CKD. STUDY DESIGN: Secondary analysis of cross-sectional data. SETTING & PARTICIPANTS: 536 patients with advanced CKD (estimated glomerular filtration rate<30mL/min/1.73m2, with or without kidney replacement therapy) from multiple clinical centers in Toronto. EXPOSURE: Racialized status (individuals who identify as Asian or as African, Caribbean, or Black Canadian), immigrant status, and combined immigrant-racialized status. OUTCOME: Psychosocial distress, defined as the presence of depression, anxiety, or social difficulties (ie, a score of≥10 points on the Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, or Social Distress 16 scales, respectively). ANALYTICAL APPROACH: The independent associations of racialized status and immigrant status with psychosocial distress, depression, anxiety, and social difficulties were examined using univariable- and multivariable-adjusted logistic regression. RESULTS: Mean age of the 536 participants was 57±16 (SD) years, 62% were male, and 45% were immigrants. Of the sample, 58% were White, 22% were African, Caribbean, or Black Canadian, and 20% were Asian. Psychosocial distress was present in 36% of participants (depression in 19%, anxiety in 12%, and social difficulties in 31%). To assess the combined impact of racialized and immigrant status, we created a variable with mutually exclusive categories: White nonimmigrant, racialized nonimmigrant, White immigrant, and racialized immigrant participants. In our final multivariable-adjusted model, compared with White nonimmigrant participants, racialized immigrant participants were more likely to have psychosocial distress (OR, 2.96 [95% CI, 1.81-4.81]), depression (OR, 1.87 [95% CI, 1.05-3.34]), and social difficulties (OR, 3.36 [95% CI, 2.03-5.57]). Overall similar associations were seen for racialized nonimmigrants and for White immigrants. LIMITATIONS: Convenience sample; small subgroups; combined exposure variable grouping Asian and African, Caribbean, and Black participants together; lack of data about mechanisms. CONCLUSIONS: Both racialized and immigrant status based on self-report of demographic characteristics were associated with psychosocial distress among patients with advanced CKD. These patients may benefit from culturally competent psychosocial support. PLAIN-LANGUAGE SUMMARY: Psychosocial distress is frequent in patients with advanced chronic kidney disease and impacts quality of life and clinical outcomes. Psychosocial distress may be especially scarring in people who are racialized (marginalized on account of their membership in a particular racial group) and/or who are immigrants. We assessed the association of psychosocial distress with racialized and immigrant status in Canadians with advanced chronic kidney disease. Among 536 participants from multiple medical centers in Toronto, we found that racialized and immigrant participants were more likely to have psychosocial distress, depression, and social difficulties compared with White nonimmigrant participants. This is likely related to the multiple intersectional challenges, including experience with racism and discrimination that racialized immigrant patients may face. Further studies are needed to elucidate the specific factors that contribute to more distress. The potential impact of culturally competent and safe support for these patients will also need to be studied.

Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized Trial.

BACKGROUND: The Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clinically measurable benefit with respect to risk of mortality or early complications with early dialysis initiation versus deferred dialysis start. After these findings, guidelines recommended an intent-to-defer approach to dialysis initiation, with the goal of deferring it until clinical symptoms arise. METHODS: To evaluate a four-component knowledge translation intervention aimed at promoting an intent-to-defer strategy for dialysis initiation, we conducted a cluster randomized trial in Canada between October 2014 and November 2015. We randomized 55 clinics, 27 to the intervention group and 28 to the control group. The educational intervention, using knowledge-translation tools, included telephone surveys from a knowledge-translation broker, a 1-year center-specific audit with feedback, delivery of a guidelines package, and an academic detailing visit. Participants included adults who had at least 3 months of predialysis care and who started dialysis in the first year after the intervention. The primary efficacy outcome was the proportion of patients who initiated dialysis early (at eGFR >10.5 ml/min per 1.73 m2). The secondary outcome was the proportion of patients who initiated in the acute inpatient setting. RESULTS: The analysis included 3424 patients initiating dialysis in the 1-year follow-up period. Of these, 509 of 1592 (32.0%) in the intervention arm and 605 of 1832 (33.0%) in the control arm started dialysis early. There was no difference in the proportion of individuals initiating dialysis early or in the proportion of individuals initiating dialysis as an acute inpatient. CONCLUSIONS: A multifaceted knowledge translation intervention failed to reduce the proportion of early dialysis starts in patients with CKD followed in multidisciplinary clinics. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT02183987. Available at: https://clinicaltrials.gov/ct2/show/NCT02183987.

Technique Failure in a Multicenter Canadian Home Hemodialysis Cohort.

RATIONALE & OBJECTIVE: Increasing uptake of home hemodialysis (HD) has led to interest in characteristics that predict discontinuation of home HD therapy for reasons other than death or transplantation. Recent reports of practice pattern variability led to the hypothesis that there are patient- and center-specific factors that influence these discontinuations. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Incident home HD patients at 7 centers in Canada between 2000 and 2010. PREDICTOR: Treatment center, case-mix, and process-of-care variables. OUTCOMES: Technique failure (defined as discontinuation of home HD therapy for any reason other than training failure, death, or transplantation) and mortality. ANALYTICAL APPROACH: Regression modeling of technique failure using Cox proportional hazard models adjusting for treatment center and modifiable and nonmodifiable patient-level variables, censored for death and transplantation. RESULTS: The cohort consisted of 579 patients. Mean age was 49.9±14.1 years, 74% were of European ancestry, median dialysis vintage was 1.9 (IQR, 0.6-5.2) years, and 68% used an arteriovenous access. Mean duration of dialysis was 31.2±12.6 hours per week. Unadjusted 1- and 2-year technique survival and overall survival were 90% and 83% and 94% and 87%, respectively. Treating center was a strong predictor of technique failure and mortality, with HRs ranging from 0.37 to 5.11 for technique failure (1 of 6 centers with P<0.05 relative to the reference) and 0.17 to 8.73 for mortality (3 of 6 centers with P<0.05 relative to the reference). With baseline adjustment for center, only older age and more than 3 treatments per week remained significant predictors of technique failure, while no individual-level variables remained as significant predictors of survival. LIMITATIONS: Limited statistical power. CONCLUSIONS: Home HD treating centers may influence technique failure and patient mortality independent of case-mix. The relationship between processes of care and patient outcomes requires further investigation.

Fit for Dialysis: a qualitative exploration of the impact of a research-based film for the promotion of exercise in hemodialysis.

BACKGROUND: Exercise improves functional outcomes and quality of life of older patients with end-stage renal disease undergoing hemodialysis. Yet exercise is not promoted as part of routine care. Health care providers and family carers rarely provide encouragement for patients to exercise, and the majority of older patients remain largely inactive. There is thus the need for a shift in the culture of hemodialysis care towards the promotion of exercise for wellness, including expectations of exercise participation by older patients, and encouragement by health care providers and family carers. Film-based educational initiatives hold promise to effect cultures of best practice, but have yet to be utilized in this population. METHODS: We developed a research-based film, Fit for Dialysis, to promote exercise for wellness in hemodialysis care. Using a qualitative approach, we evaluated the effects that resulted from engagement with this film (e.g. knowledge/attitudes regarding the importance of exercise-based principles of wellness) as well as the generative mechanisms of these effects (e.g. realism, aesthetics). We also explored the factors related to patients, family carers, and health care providers that influenced engagement with the film, and the successful uptake of the key messages of Fit for Dialysis. We conducted qualitative interviews with 10 patients, 10 health care providers, and 10 family carers. Data were analyzed using thematic analysis. RESULTS: The film was perceived to be effective in increasing patients', family carers' and health care providers' understanding of the importance of exercise and its benefits, motivating patients to exercise, and in increasing encouragement by family carers and health care providers of patient exercise. Realism (e.g. character identification) and aesthetic qualities of the film (e.g. dialogue) were identified as central generative mechanisms. CONCLUSIONS: Fit for Dialysis is well-positioned to optimize the health and wellbeing of older adults undergoing hemodialysis. TRIAL REGISTRATION: NCT02754271 ( ClinicalTrials.gov ), retroactively registered on April 21, 2016.

The Risk of Major Hemorrhage with CKD.

New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002-2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m(2)) and urine albumin-to-creatinine ratio (ACR; >300, 30-300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m(2) had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.

Pro: Buttonhole cannulation of arteriovenous fistulae.

Arteriovenous fistulae remain the access of choice for most hemodialysis patients. However, several factors limit their uptake and long-term patency, resulting in suboptimal prevalent rates in many high-income countries. Patients place considerable value on the avoidance of vascular access complications, pain and disfigurement. The approach to cannulation is a modifiable practice that could improve patient-important outcomes, with buttonhole needling offering some theoretical advantages over the standard rope-ladder and area methods. In this narrative review, we summarize key findings of studies reporting the benefits and risks associated with the buttonhole method, highlighting methodological limitations as well as recent refinements to the technique that may represent potential opportunities for reducing infection risk. We highlight the need for greater certainty surrounding the potential benefits of the buttonhole cannulation technique and propose some directions for future research.

The risk of hospitalization and modality failure with home dialysis.

While home dialysis is being promoted, there are few comparative effectiveness studies of home-based modalities to guide patient decisions. To address this, we matched 1116 daily home hemodialysis (DHD) patients by propensity scores to 2784 contemporaneous USRDS patients receiving home peritoneal dialysis (PD), and compared hospitalization rates from cardiovascular, infectious, access-related or bleeding causes (prespecified composite), and modality failure risk. We performed similar analyses for 1187 DHD patients matched to 3173 USRDS patients receiving in-center conventional hemodialysis (CHD). The composite hospitalization rate was significantly lower with DHD than with PD (0.93 vs. 1.35/patient-year, hazard ratio=0.73 (95% CI=0.67-0.79)). DHD patients spent significantly fewer days in hospital than PD patients (5.2 vs. 9.2 days/patient-year), and significantly more DHD patients remained admission-free (52% DHD vs. 32% PD). In contrast, there was no significant difference in hospitalizations between DHD and CHD (DHD vs. CHD: 0.93 vs. 1.10/patient-year, hazard ratio 0.92 (0.85-1.00)). Cardiovascular hospitalizations were lower with DHD than with CHD (0.68 (0.61-0.77)), while infectious and access hospitalizations were higher (1.15 (1.04-1.29) and 1.25 (1.08-1.43), respectively). Significantly more PD than DHD patients switched back to in-center HD (44% vs. 15%; 3.4 (2.9-4.0)). In this prevalent cohort, home DHD was associated with fewer admissions and hospital days than PD, and a substantially lower risk of modality failure.

High-performance information search filters for CKD content in PubMed, Ovid MEDLINE, and EMBASE.

BACKGROUND: Finding relevant articles in large bibliographic databases such as PubMed, Ovid MEDLINE, and EMBASE to inform care and future research is challenging. Articles relevant to chronic kidney disease (CKD) are particularly difficult to find because they are often published under different terminology and are found across a wide range of journal types. STUDY DESIGN: We used computer automation within a diagnostic test assessment framework to develop and validate information search filters to identify CKD articles in large bibliographic databases. SETTING & PARTICIPANTS: 22,992 full-text articles in PubMed, Ovid MEDLINE, or EMBASE. INDEX TEST: 1,374,148 unique search filters. REFERENCE TEST: We established the reference standard of article relevance to CKD by manual review of all full-text articles using prespecified criteria to determine whether each article contained CKD content or not. We then assessed filter performance by calculating sensitivity, specificity, and positive predictive value for the retrieval of CKD articles. Filters with high sensitivity and specificity for the identification of CKD articles in the development phase (two-thirds of the sample) were then retested in the validation phase (remaining one-third of the sample). RESULTS: We developed and validated high-performance CKD search filters for each bibliographic database. Filters optimized for sensitivity reached at least 99% sensitivity, and filters optimized for specificity reached at least 97% specificity. The filters were complex; for example, one PubMed filter included more than 89 terms used in combination, including "chronic kidney disease," "renal insufficiency," and "renal fibrosis." In proof-of-concept searches, physicians found more articles relevant to the topic of CKD with the use of these filters. LIMITATIONS: As knowledge of the pathogenesis of CKD grows and definitions change, these filters will need to be updated to incorporate new terminology used to index relevant articles. CONCLUSIONS: PubMed, Ovid MEDLINE, and EMBASE can be filtered reliably for articles relevant to CKD. These high-performance information filters are now available online and can be used to better identify CKD content in large bibliographic databases.

Using the knowledge-to-action framework to guide the timing of dialysis initiation.

PURPOSE OF REVIEW: The optimal time at which to initiate chronic dialysis remains unknown. Using a contemporary knowledge translation approach (the knowledge-to-action framework), a pan-Canadian collaboration (CANN-NET) set out to study the scope of the problem, then develop and disseminate evidence-based guidelines addressing the timing of dialysis initiation. The purpose of this review is to summarize the key findings and describe the planned Canadian knowledge translation strategy for improving knowledge and practices pertaining to the timing dialysis initiation. RECENT FINDINGS: New research has provided considerable insights regarding the initiation of dialysis. A Canadian cohort study identified significant variation in the estimated glomerular filtration rate level at dialysis initiation, and a survey of providers identified related knowledge gaps that might be amenable to knowledge translation interventions. A recent knowledge synthesis/guideline concluded that early dialysis initiation is costly, and provides no measureable clinical benefits. A systematic knowledge translation intervention including a multifaceted approach may aid in reducing variation in practice and improving the quality of care. SUMMARY: Utilizing the knowledge-to-action framework, we identified practice variation and key barriers to the optimal timing for dialysis initiation that may be amenable to knowledge translation strategies.

Buttonhole versus rope-ladder cannulation of arteriovenous fistulas for hemodialysis: a systematic review.

BACKGROUND: The buttonhole technique is an alternative method of cannulating the arteriovenous fistula (AVF) in hemodialysis (HD), frequently used for home HD patients. However, the balance of risks and benefits of the buttonhole compared with the rope-ladder technique is uncertain. STUDY DESIGN: A systematic review of randomized trials and observational studies (case reports, case series, studies without a control group, non-English studies, and abstracts were excluded). SETTING & POPULATION: HD patients (both in-center conventional HD and home HD) using an AVF for vascular access. SELECTION CRITERIA FOR STUDIES: We searched MEDLINE, EMBASE, EBM Reviews, and CINAHL from the earliest date in the databases to March 2014 for studies comparing clinical outcomes of the buttonhole versus rope-ladder technique. INTERVENTION: Buttonhole versus rope-ladder cannulation technique. OUTCOMES: The primary outcomes of interest were patient-reported cannulation pain and rates of AVF-related local and systemic infections. Secondary outcomes included access survival, intervention, hospitalization, and mortality, as well as hematoma and aneurysm formation, time to hemostasis, and all-cause hospitalization and mortality. RESULTS: Of 1,044 identified citations, 23 studies were selected for inclusion. There was equivocal evidence with respect to cannulation pain: pooled observational studies yielded a statistical reduction in pain with buttonhole cannulation (standardized mean difference, -0.76 [95%CI, -1.38 to -0.15] standard deviations), but no difference in cannulation pain was found among randomized controlled trials (standardized mean difference, 0.34 [95%CI, -0.76 to 1.43] standard deviations). Buttonhole, as compared to rope-ladder, technique appeared to be associated with increased risk of local and systemic infections. LIMITATIONS: Overall poor quality and substantial heterogeneity among studies precluded pooling of most outcomes. CONCLUSIONS: Evidence does not support the preferential use of buttonhole over rope-ladder cannulation in either facility-based conventional HD or home HD. This does not preclude buttonhole cannulation as being appropriate for some patients with difficult-to-access AVFs.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant.

Identification of facilitators and barriers to home dialysis selection by canadian adults with ESRD.

Home dialysis (home HD or home PD) remains underutilized in most jurisdictions. Physicians, advanced-practice nurses, and policy makers working with chronic kidney disease populations can provide insights into patient, healthcare professional, and system-level barriers to home dialysis selection by suitable patients. We used in-depth interviews, with a purposive sampling strategy until informational redundancy was achieved, to elicit barriers and facilitators to home dialysis selection from thirteen informants. We triangulated these data against qualitative data collected in a related survey of nephrologist attitudes. We used a modified grounded theory approach to construct a taxonomy of barriers and facilitators. Informants included nephrologists (n = 11), an advanced-practice nurse, and a health administrator with a provincial renal care organization. We constructed separate taxonomies of barriers and related facilitators that were specific to PD, specific to home HD, and common to both. We distinguished between factors favoring, modifiable factors opposing, and nonmodifiable factors opposing home dialysis selection. Several major themes emerged, including: medical factors, home physical environment, psychological and cognitive factors (knowledge, attitudes, coping styles), social factors (supports, lifestyle), dialysis program, local hospital or regional factors (expertise, resources, local culture), healthcare professional-related factors (knowledge, attitudes, reimbursement), health system-related factors (funding models), and exogenous factors (late referral, technology). We identified several modifiable practices at the level of patient, healthcare professional, dialysis facility, and healthcare system to increase appropriate use of home dialysis. We discuss potential facilitating factors, knowledge gaps, and priorities for future research, and propose potential applications for this novel taxonomy of determinants of dialysis modality choice.

A multinational cohort study of in-center daily hemodialysis and patient survival.

Increasing hemodialysis frequency from three to six times per week improves left-ventricular mass and health-related quality of life; however, effects on survival remain uncertain. To study this, we identified 556 patients in the International Quotidian Dialysis Registry who received daily hemodialysis (more than five times per week) between 2001 and 2010. Using propensity score-based matching, we matched 318 of these patients to 575 contemporaneous patients receiving conventional (three times weekly) hemodialysis in the Dialysis Outcomes and Practice Patterns Study. All patients had session times of <5 h, and received dialysis in the clinic or hospital setting. Mortality rates between groups were compared using Cox proportional hazards regression. Mean dialysis frequency in the daily group was 5.8 sessions per week. Mean weekly treatment time was 15.7 h for daily and 11.9 h for conventional patients. During 1382 patient-years of follow-up, 170 patients died. Those receiving daily hemodialysis had a significantly higher mortality rate than those receiving conventional hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard ratio 1.6). Similar results were found in prespecified subgroup and sensitivity analyses. Unlike previous studies, we found that in-center daily hemodialysis was not associated with any mortality benefit. Thus, decisions to undertake daily hemodialysis should be based on quality-of-life improvements, rather than on claims of improved survival.

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.

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.

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.

Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis.

BACKGROUND: Intradialytic hypotension (IDH) is associated with morbidity and mortality. We conducted a systematic review to determine whether biofeedback hemodialysis (HD) can improve IDH and other outcomes, compared with HD without biofeedback. METHODS: Data sources included the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ISI Web of Science. We included randomized trials that enrolled adult patients (>18 years) with IDH or extracellular fluid expansion and that used biofeedback to guide ultrafiltration and/or dialysate conductivity. Two authors assessed trial quality and independently extracted data in duplicate. We assessed heterogeneity using I(2). We applied the GRADE framework for rating the quality of evidence. RESULTS: We found two parallel-arm randomized controlled clinical trials and six randomized crossover trials meeting inclusion criteria. All trials were open-label and at least four were industry-sponsored. Studies were small (median n = 27). No study evaluated hospitalization and the evidence for effect on mortality was of very low quality. Three studies assessed quality of life (QoL); none demonstrated benefit or harm, and quality of evidence was very low. Biofeedback significantly reduced IDH (risk ratio 0.61, 95% confidence interval 0.44-0.86; I(2)= 0%). Quality of evidence for this outcome was low due to risk of bias and potential publication bias. CONCLUSIONS: Biofeedback dialysis significantly reduces the frequency of IDH. Large and well-designed randomized trials are needed to assess the effects on survival, hospitalization and QoL.

A systematic review of buttonhole cannulation practices and outcomes.

Buttonhole (constant site) cannulation has emerged as an attractive technique for needling arteriovenous fistulae. However, the balance of benefits and harms associated with this intervention is unclear. We conducted a systematic review of studies reporting outcomes with buttonhole cannulation. The setting and population included adult patients receiving home or center hemodialysis. We searched MEDLINE, Embase (1980-June 2012), and CINAHL (1997-June 2012), for randomized and observational studies. We also searched conference proceedings (2009-2011). The interventions included: 1) buttonhole cannulation established by sharp needles, with or without a polycarbonate peg, 2) rope-ladder cannulation. Outcomes of interest included: Facility practices, systemic infection, local infection, access survival, access interventions, access-related hospitalization, patient survival, pain, quality of life, and aneurysm formation. We identified 23 full-text articles and 4 abstracts; 3 were open-label trials, and the remainder observational studies of varying design and methodological quality. Studies were predominantly descriptive and lacked direct comparisons between buttonhole and rope-ladder cannulation. No qualitative differences in outcomes were noted among home and center hemodialysis patients using buttonhole cannulation. Rates of bacteremia were generally higher with buttonhole cannulation. Studies reporting access survival, hospitalization, quality of life, pain, and aneurysm formation had serious methodological limitations that limited our confidence in their estimates of effect. Among the various facility practices that were described, only the application of mupirocin cream was noted to be associated with reduced risk of infection. Limitations in included studies were short follow-up, crossover designs, lack of parallel control groups, and the use of patient-reported outcome measures that were not well validated. The main limitation of this review was a limited literature search. Buttonhole cannulation may be associated with an increased risk of infection. Larger, more definitive studies are needed to determine whether this technique is safe for broader use.

Survival with three-times weekly in-center nocturnal versus conventional hemodialysis.

Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during 2 years of follow-up in a 1:3 propensity score-matched cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis. Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61-0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score-matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials.

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.