Global variations in funding and use of hemodialysis accesses: an international report using the ISN Global Kidney Health Atlas.

BACKGROUND: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. METHODS: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. RESULTS: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). CONCLUSIONS: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Patient and Clinician Perspectives on Shared Decision Making in Vascular Access Selection: A Qualitative Study.

RATIONALE & OBJECTIVE: Collaborative approaches to vascular access selection are being increasingly encouraged to elicit patients' preferences and priorities where no unequivocally superior choice exists. We explored how patients, their caregivers, and clinicians integrate principles of shared decision making when engaging in vascular access discussions. STUDY DESIGN: Qualitative description. SETTING & PARTICIPANTS: Semistructured interviews with a purposive sample of patients, their caregivers, and clinicians from outpatient hemodialysis programs in Alberta, Canada. ANALYTICAL APPROACH: We used a thematic analysis approach to inductively code transcripts and generate themes to capture key concepts related to vascular access shared decision making across participant roles. RESULTS: 42 individuals (19 patients, 2 caregivers, 21 clinicians) participated in this study. Participants identified how access-related decisions follow a series of major decisions about kidney replacement therapy and care goals that influence vascular access preferences and choice. Vascular access shared decision making was strengthened through integration of vascular access selection with dialysis-related decisions and timely, tailored, and balanced exchange of information between patients and their care team. Participants described how opportunities to revisit the vascular access decision before and after dialysis initiation helped prepare patients for their access and encouraged ongoing alignment between patients' care priorities and treatment plans. Where shared decision making was undermined, hemodialysis via a catheter ensued as the most readily available vascular access option. LIMITATIONS: Our study was limited to patients and clinicians from hemodialysis care settings and included few caregiver participants. CONCLUSIONS: Findings suggest that earlier, or upstream, decisions about kidney replacement therapies influence how and when vascular access decisions are made. Repeated vascular access discussions that are integrated with other higher-level decisions are needed to promote vascular access shared decision making and preparedness.

Health related quality of life during dialysis modality transitions: a qualitative study.

BACKGROUND: Modality transitions represent a period of significant change that can impact health related quality of life (HRQoL). We explored the HRQoL of adults transitioning to new or different dialysis modalities. METHODS: We recruited eligible adults (≥ 18) transitioning to dialysis from pre-dialysis or undertaking a dialysis modality change between July and September 2017. Nineteen participants (9 incident and 10 prevalent dialysis patients) completed the KDQOL-36 survey at time of transition and three months later. Fifteen participants undertook a semi-structured interview at three months. Qualitative data were thematically analyzed. RESULTS: Four themes and five sub-themes were identified: adapting to new circumstances (tackling change, accepting change), adjusting together, trading off, and challenges of chronicity (the impact of dialysis, living with a complex disease, planning with uncertainty). From the first day of dialysis treatment to the third month on a new dialysis therapy, all five HRQoL domains from the KDQOL-36 (symptoms, effects, burden, overall PCS, and overall MCS) improved in our sample (i.e., those who remained on the modality). CONCLUSIONS: Dialysis transitions negatively impact the HRQoL of people with kidney disease in various ways. Future work should focus on how to best support people during this time.

Advancing Exercise Science for Better Health Outcomes Across the Spectrum of Chronic Kidney Disease.

Despite over 30 years of evidence for improvements in physical function, physical fitness, and health-related quality of life with exercise training in individuals with chronic kidney disease, access to dedicated exercise training programs remains outside the realm of standard of care for most kidney care programs. In this review, we explore possible reasons for this by comparing approaches in other chronic diseases where exercise rehabilitation has become the standard of care, identifying enablers and factors that need to be addressed for continued growth in this area, and discussing knowledge gaps for future research. For exercise rehabilitation to be relevant to all stakeholders and become a sustainable component of kidney care, a focus on the effect of exercise on clinically relevant outcomes that are prioritized by individuals living with kidney disease, use of evidence-based implementation strategies for diverse settings and populations, and approaching exercise as a medical therapy are required.

Addressing feasibility challenges to delivering intradialytic exercise interventions: a theory-informed qualitative study.

BACKGROUND: Intradialytic exercise (IDE) may improve physical function and health-related quality of life. However, incorporating IDE into standard hemodialysis care has been slow due to feasibility challenges. We conducted a multicenter qualitative feasibility study to identify potential barriers and enablers to IDE and generate potential solutions to these factors. METHODS: We conducted 43 semistructured interviews with healthcare providers and patients across 12 hospitals in Ontario, Canada. We used the Theoretical Domains Framework and directed content analysis to analyze the data. RESULTS: We identified eight relevant domains (knowledge, skills, beliefs about consequences, beliefs about capabilities, environmental context and resources, goals, social/professional role and identity, and social influences) represented by three overarching categories: knowledge, skills and expectations: lack of staff expertise to oversee exercise, uncertainty regarding exercise risks, benefits and patient interest, lack of knowledge regarding exercise eligibility; human, material and logistical resources: staff concerns regarding workload, perception that exercise professionals should supervise IDE, space, equipment and scheduling conflict concerns; and social dynamics of the unit: local champions and patient stories contribute to IDE sustainability. We developed a list of actionable solutions by mapping barriers and enablers to behavior change techniques. We also developed a feasibility checklist of 47 questions identifying key factors to address prior to IDE launch. CONCLUSIONS: Evidence-based solutions to identified barriers to and enablers of IDE and a feasibility checklist may help recruit and support units, staff and patients and address key challenges to the delivery of IDE in diverse clinical and research settings.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

Reasons for Nonparticipation in a Sustained Hemodialysis Intradialytic Exercise Program.

OBJECTIVE(S): Patients with end-stage kidney disease requiring hemodialysis suffer frailty and poor physical function. Exercise can improve physical function; however, barriers exist to intradialytic exercise programs. The objective of this study was to explore patients' reasons for not exercising in an extant intradialytic exercise program. DESIGN AND METHODS: We conducted a retrospective analysis reporting the reasons for not exercising in an intradialytic exercise program in two hemodialysis centers over a 4-week period. We explored whether patient characteristics and the presence of an exercise professional were associated with missed exercise sessions. RESULTS: Seventy-five patients participating in the intradialytic exercise program completed 57% of prescribed intradialytic exercise sessions. The three most frequently reported reasons from patients not exercising were refusal (24%), followed by fatigue (19%) and symptoms (14%). Patients were more than twice as likely to exercise if a kinesiologist was present (odds ratio [OR]: 2.26, confidence interval [CI]: 1.5, 3.4 P = .03). They were less likely to exercise if they were women (OR: 0.66, CI: 0.45, 0.95 P = .002), had been on dialysis greater than 60 months (OR: 0.55, CI: 0.37, 0.80 P < .002), or had more than two comorbid conditions (OR: 0.63, CI: 0.43, 0.90, P = .01). CONCLUSION: Patient adherence to intradialytic exercise programs is strongly associated with the presence of exercise professionals.

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.

Outcomes of the First and Second Hemodialysis Fistula: A Cohort Study.

RATIONALE & OBJECTIVE: Fistulas are the preferred form of hemodialysis access; however, many fistulas fail to mature into usable accesses after creation. Data for outcomes after placement of a second fistula are limited. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: People who initiated hemodialysis therapy in any of 5 Canadian dialysis programs (2004-2012) and had at least 1 hemodialysis fistula placed. PREDICTOR: Second versus initial fistula; receipt of 2 versus 1 fistula; second versus first fistula in recipients of 2 fistulas. OUTCOMES: Catheter-free fistula use during 1 year following initiation of hemodialysis therapy or following fistula creation, if created after hemodialysis therapy start; proportion of time with catheter-free use; time to catheter free use; time of functional patency. ANALYTICAL APPROACH: Logistic regression; fractional regression. RESULTS: Among the 1,091 study participants (mean age, 64±15 [SD] years; 63% men; 59% with diabetes), 901 received 1 and 190 received 2 fistulas. 38% of second fistulas versus 46% of first fistulas were used catheter free at least once. Average percentages of time that second and initial fistulas were used catheter free were 34% and 42%, respectively (OR, 0.72; 95% CI, 0.54-0.94). Compared with people who received 1 fistula, those who received 2 fistulas were less likely to achieve catheter-free use (26% vs 56%) and remain catheter free (23% vs 49% of time; OR, 0.30, 95% CI, 0.24-0.39). Among people who received 2 fistulas, the proportion of time that the second fistula was used catheter free was 11% higher with each 10% greater proportion of time that the first fistula was used catheter free (95% CI, 1%-22%). Model discrimination was modest (C index, 0.69). LIMITATIONS: Unknown criteria for patient selection for 1 or 2 fistulas; unknown reasons for prolonged catheter use. CONCLUSIONS: Outcomes of a second fistula may be inferior to outcomes of the initial fistula. First and second fistula outcomes are weakly correlated and difficult to predict based on clinical characteristics.

Can economic incentives increase the use of home dialysis?

There are advantages to home dialysis for patients, and kidney care programs, but use remains low in most countries. Health-care policy-makers have many levers to increase use of home dialysis, one of them being economic incentives. These include how health-care funding is provided to kidney care programs and dialysis facilities; how physicians are remunerated for care of home dialysis patients; and financial incentives-or removal of disincentives-for home dialysis patients. This report is based on a comprehensive literature review summarizing the impact of economic incentives for home dialysis and a workshop that brought together an international group of policy-makers, health economists and home dialysis experts to discuss how economic incentives (or removal of economic disincentives) might be used to increase the use of home dialysis. The results of the literature review and the consensus of workshop participants were that financial incentives to dialysis facilities for home dialysis (for instance, through activity-based funding), particularly in for-profit systems, could lead to a small increase in use of home dialysis. The evidence was less clear on the impact of economic incentives for nephrologists, and participants felt this was less important than a nephrologist workforce in support of home dialysis. Workshop participants felt that patient-borne costs experienced by home dialysis patients were unjust and inequitable, though participants noted that there was no evidence that decreasing patient-borne costs would increase use of home dialysis, even among low-income patients. The use of financial incentives for home dialysis-whether directed at dialysis facilities, nephrologists or patients-is only one part of a high-performing system that seeks to increase use of home dialysis.

The role of exercise in improving patient-reported outcomes in individuals on dialysis: A scoping review.

Exercise improves objective measures of physical function in individuals on hemodialysis, but its effect on patient-reported outcomes (PROs) is largely unknown. We performed a scoping review to characterize the existing knowledge base on exercise and PROs in dialysis patients to make recommendations for future research. We searched Medline, Embase, Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials, CINAHL, and SPORT Discus from inception to November 28, 2018 and then screened results for randomized controlled trials comparing aerobic/resistance exercise, or both, with no exercise in individuals on dialysis that reported results of any PRO. Of 1374 eligible studies, 25 studies met inclusion criteria. Study interventions included aerobic exercise (11 intradialytic and 3 home-based trials); intradialytic resistance exercise (seven studies) and combined aerobic and resistance exercise (six intradialytic and one facility-based trial). The PROs measured included health-related quality of life (n = 19), depression (n = 6), anxiety (n = 3), symptom burden (n = 4), sleep quality (n = 2), restless legs syndrome (n = 2), disability (n = 2), and self-reported physical activity level (n = 4). Only five studies included a PRO as a primary outcome. Studies primarily used broad/generic measures of health-related quality of life and the effect of exercise on symptoms remains relatively unexplored, particularly in peritoneal dialysis populations. Although limited, the role of exercise in improving restless legs was consistent and is a promising outcome for future study. A critical step to improving the quality of the research on this topic includes the use of validated and consistent PRO measures.

Central venous catheters for chronic hemodialysis: Is "last choice" never the "right choice"?

Since the publication of the first vascular access clinical practice guidelines in 1997, the global nephrology community has dedicated significant time and resources toward increasing the prevalence of arteriovenous fistulas and decreasing the prevalence of central venous catheters for hemodialysis. These efforts have been bolstered by observational studies showing an association between catheter use and increased patient morbidity and mortality. To date, however, no randomized comparisons of the outcomes of different forms of vascular access have been conducted. There is mounting evidence that much of the difference in patient outcomes may be explained by patient factors, rather than choice of vascular access. Some have called into question the appropriateness of fistula creation for certain patient populations, such as those with limited life expectancy and those at high risk of fistula-related complications. In this review, we explore the extent to which catheters and fistulas exhibit the characteristics of the "ideal" vascular access and highlight the significant knowledge gaps that exist in the current literature. Further studies, ideally randomized comparisons of different forms of vascular access, are required to better inform shared decision making.

A comparison of temporal artery thermometers with internal blood monitors to measure body temperature during hemodialysis.

BACKGROUND: Thermometers that measure core (internal) body temperature are the gold standard for monitoring temperature. Despite that most modern hemodialysis machines are equipped with an internal blood monitor that measures core body temperature, current practice is to use peripheral thermometers. A better understanding of how peripheral thermometers compare with the dialysis machine thermometer may help guide practice. METHODS: The study followed a prospective cross-sectional design. Hemodialysis patients were recruited from 2 sites in Calgary, Alberta (April - June 2017). Body temperatures were obtained from peripheral (temporal artery) and dialysis machine thermometers concurrently. Paired t-tests, Bland-Altman plots, and quantile-quantile plots were used to compare measurements from the two devices and to explore potential factors affecting temperature in hemodialysis patients. RESULTS: The mean body temperature of 94 hemodialysis patients measured using the temporal artery thermometer (36.7 °C) was significantly different than the dialysis machine thermometer (36.4 °C); p < 0.001. The mean difference (0.27 °C) appeared to be consistent across average temperature (range: 35.8-37.3 °C). CONCLUSIONS: Temperature measured by the temporal artery thermometer was statistically and clinically higher than that measured by the dialysis machine thermometer. Using the dialysis machine to monitor body temperature may result in more accurate readings and is likely to reduce the purchasing and maintenance costs associated with manual temperature readings, as well as easing the workload for dialysis staff.

The Effect of Predialysis Fistula Attempt on Risk of All-Cause and Access-Related Death.

Whether the lower risk of mortality associated with arteriovenous fistula use in hemodialysis patients is due to the avoidance of catheters or if healthier patients are simply more likely to have fistulas placed is unknown. To provide clarification, we determined the proportion of access-related deaths in a retrospective cohort study of patients aged ≥18 years who initiated hemodialysis between 2004 and 2012 at five Canadian dialysis programs. A total of 3168 patients initiated dialysis at the participating centers; 2300 met our inclusion criteria. Two investigators independently adjudicated cause of death using explicit criteria and determined whether a death was access-related. We observed significantly lower mortality in individuals who underwent a predialysis fistula attempt than in those without a predialysis fistula attempt in patients aged <65 years (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.29 to 0.82) and in the first 2 years of follow-up in those aged ≥65 years (HR0-24 months, 0.60; 95% CI, 0.43 to 0.84; HR24+ months, 1.83; 95% CI, 1.25 to 2.67). Sudden deaths that occurred out of hospital accounted for most of the deaths, followed by deaths due to cardiovascular disease and infectious complications. We found only 2.3% of deaths to be access-related. In conclusion, predialysis fistula attempt may associate with a lower risk of mortality. However, the excess mortality observed in patients treated with catheters does not appear to be due to direct, access-related complications but is likely the result of residual confounding, unmeasured comorbidity, or treatment selection bias.

A Clinical Risk Prediction Tool for 6-Month Mortality After Dialysis Initiation Among Older Adults.

BACKGROUND: Information on an individual's risk for death following dialysis therapy initiation may inform the decision to initiate maintenance dialysis for older adults. We derived and validated a clinical risk prediction tool for all-cause mortality among older adults during the first 6 months of maintenance dialysis treatment. STUDY DESIGN: Prediction model using retrospective administrative and clinical data. SETTING & PARTICIPANTS: We linked administrative and clinical data to define a cohort of 2,199 older adults (age ≥ 65 years) in Alberta, Canada, who initiated maintenance dialysis therapy (excluding acute kidney injury) in May 2003 to March 2012. CANDIDATE PREDICTORS: Demographics, laboratory data, comorbid conditions, and measures of health system use. OUTCOMES: All-cause mortality within 6 months of dialysis therapy initiation. ANALYTICAL APPROACH: Predicted mortality by logistic regression with 10-fold cross-validation. RESULTS: 375 (17.1%) older adults died within 6 months. We developed a 19-point risk score for 6-month mortality that included age 80 years or older (2 points), glomerular filtration rate of 10 to 14.9mL/min/1.73m2 (1 point) or ≥15mL/min/1.73m2 (3 points), atrial fibrillation (2 points), lymphoma (5 points), congestive heart failure (2 points), hospitalization in the prior 6 months (2 points), and metastatic cancer (3 points). Model discrimination (C statistic = 0.72) and calibration (Hosmer-Lemeshow χ2=10.36; P=0.2) were reasonable. As examples, a score < 5 equated to <25% of individuals dying in 6 months, whereas a score > 12 predicted that more than half the individuals would die in the first 6 months. LIMITATIONS: The tool has not been externally validated; thus, generalizability cannot be assessed. CONCLUSIONS: We used readily available clinical information to derive and internally validate a 7-variable tool to predict early mortality among older adults after dialysis therapy initiation. Following successful external validation, the tool may be useful as a clinical decision tool to aid decision making for older adults with kidney failure.

Impact of using two dialyzers in parallel on phosphate clearance in hemodialysis patients: a randomized trial.

BACKGROUND: Dietary restriction and phosphate binders are the main interventions used to manage hyperphosphatemia in people on hemodialysis, but have limited efficacy. Modifying conventional dialysis regimens to enhance phosphate clearance as an alternative approach remains relatively unstudied. METHODS: This was a 10-week, 2-arm, randomized crossover study. Participants were prevalent dialysis patients ( n = 32) with consecutive serum phosphate levels >1.6 mmol/L and on stable doses of a phosphate binder. Following a 2-week run-in period, participants were randomized to initiate dialysis using two high flux dialyzers in parallel (blood flow ≥350 mL/min, dialysate flow 800 mL/min) or standard dialysis using one high flux dialyzer (blood flow ≥350 mL/min, dialysate flow of 800 mL/min). Each regimen was 3 weeks in duration. After a 2-week washout period, participants received the alternate regimen. The primary outcome was the mean difference in phosphate clearance by dialyzer strategy. Secondary outcomes were phosphate removal and pre-dialysis serum phosphate. RESULTS: Phosphate clearance for the double dialyzer strategy did not differ significantly from the single dialyzer strategy [mean difference 7.5 mL/min (95% confidence interval, 95% CI, -6.1, 21.0), P = 0.28]. There was no difference in total phosphate removal and pre-dialysis phosphate between the double and single dialyzer strategies [total phosphate removal mean difference -0.2 mmol (95% CI -4.1, 3.7), P = 0.93; pre-dialysis mean difference 0.01 mmol/L (95% CI -0.18, 0.21), P = 0.88]. There was no difference in the proportion of participants who experienced at least one episode of intradialytic hypotension (32 versus 47%, P = 0.13). A limitation of the study was frequent protocol deviations in the dialysis prescription. CONCLUSIONS: In this study, the use of two dialyzers in parallel did not increase phosphate clearance, phosphate removal or pre-dialysis serum phosphorus when compared with a standard dialysis treatment strategy. Future studies should continue to evaluate novel methods of phosphate removal using conventional hemodialysis.

Sex differences in associations between insulin resistance, heart rate variability, and arterial stiffness in healthy women and men: a physiology study.

Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted.

Preemptive Correction of Arteriovenous Access Stenosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Preemptive correction of a stenosis in an arteriovenous (AV) access (fistula or graft) that is adequately providing hemodialysis (functional AV access) may prolong access survival as compared to waiting for signs of access dysfunction to intervene (deferred salvage). However, the evidence in support of preemptive intervention is controversial. We evaluated benefits and harms of preemptive versus deferred correction of AV access stenosis. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION: Adults receiving hemodialysis by a functional AV access. SELECTION CRITERIA FOR STUDIES: We searched the Cochrane Kidney and Transplant Specialised Register and EMBASE to October 15, 2015. INTERVENTION: Active access surveillance (flow measurement and Doppler or venous pressure) and preemptive correction of a newly identified stenosis versus routine clinical monitoring and deferred salvage, or preemptive correction of a known stenosis versus deferred salvage. OUTCOMES: Access loss (primary outcome) and thrombosis (overall and by access type), infection, mortality, hospitalization, and access-related procedures. RESULTS: We included 14 trials (1,390 participants; follow-up, 6-38 months). Relative to deferred salvage, preemptive correction of AV access stenosis had a nonsignificant effect on risk for access loss (risk ratio [RR], 0.81; 95% CI, 0.65-1.02; I(2)=0%) and a significant effect on risk for thrombosis (RR, 0.79; 95% CI, 0.65-0.97; I(2)=30%). Treatment effects were larger in fistulas than in grafts for both risk for access loss (subgroup difference, P=0.05) and risk for thrombosis (subgroup difference, P=0.002). Results were heterogeneous or imprecise for mortality, rates of access-related infections or procedures, and hospitalization. LIMITATIONS: Small number and size of primary studies limited analysis power. CONCLUSIONS: Preemptive stenosis correction in a functional AV access does not improve access longevity. Although preemptive stenosis correction may be promising in fistulas, existing evidence is insufficient to guide clinical practice and health policy.

Pre-emptive correction for haemodialysis arteriovenous access stenosis.

BACKGROUND: Guidelines recommend routine arteriovenous (AV) graft and fistula surveillance (technology-based screening) in addition to clinical monitoring (physical examination) for early identification and pre-emptive correction of a stenosis before the access becomes dysfunctional. However, consequences on patient-relevant outcomes of pre-emptive correction of a stenosis in a functioning access as opposed to deferred correction, i.e. correction postponed to when the access becomes dysfunctional, are uncertain. OBJECTIVES: We aimed to evaluate 1) whether pre-emptive correction of an AV access stenosis improves clinically relevant outcomes; 2) whether the effects of pre-emptive correction of an AV access stenosis differ by access type (fistula versus graft), aim (primary and secondary prophylaxis), and surveillance method for primary prophylaxis (Doppler ultrasound for the screening of functional and anatomical changes versus measurement of the flow in the access); and 3) whether other factors (dialysis duration, access location, configuration or materials, algorithm for referral for intervention, intervention strategies (surgical versus radiological or other), or study design) explain the heterogeneity that might exist in the effect estimates. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2015 using search terms relevant to this review. SELECTION CRITERIA: We included all studies of any access surveillance method for early identification and pre-emptive treatment of an AV access stenosis. DATA COLLECTION AND ANALYSIS: We extracted data on potentially remediable and irremediable failure of the access (i.e. thrombosis and access loss respectively); infection and mortality; and resource use (hospitalisation, diagnostic and intervention procedures). Analysis was by a random effects model and results expressed as risk ratio (RR), hazard ratio (HR) or incidence rate ratio (IRR) with 95% confidence intervals (CI). MAIN RESULTS: We identified 14 studies (1390 participants), nine enrolled adults without a known access stenosis (primary prophylaxis; three studies including people using fistulas) and five enrolled adults with a documented stenosis in a non-dysfunctional access (secondary prophylaxis; three studies in people using fistulas). Study follow-up ranged from 6 to 38 months, and study size ranged from 58 to 189 participants. In low- to moderate-quality evidence (based on GRADE criteria) in adults treated with haemodialysis, relative to no surveillance and deferred correction, surveillance with pre-emptive correction of an AV stenosis reduced the risk of thrombosis (RR 0.79, 95% CI 0.65 to 0.97; I² = 30%; 18 study comparisons, 1212 participants), but had imprecise effect on the risk of access loss (RR 0.81, 95% CI 0.65 to 1.02; I² = 0%; 11 study comparisons, 972 participants). In analyses subgrouped by access type, pre-emptive stenosis correction did not reduce the risk of thrombosis (RR 0.95, 95% CI 0.8 to 1.12; I² = 0%; 11 study comparisons, 697 participants) or access loss in grafts (RR 0.9, 95% CI 0.71 to 1.15; I² = 0%; 7 study comparisons; 662 participants), but did reduce the risk of thrombosis (RR 0.5, 95% CI 0.35 to 0.71; I² = 0%; 7 study comparisons, 515 participants) and the risk of access loss in fistulas (RR 0.5, 95% CI 0.29 to 0.86; I² = 0%; 4 studies; 310 participants). Three of the four studies reporting access loss data in fistulas (199 participants) were conducted in the same centre. Insufficient data were available to assess whether benefits vary by prophylaxis aim in fistulas (i.e. primary and secondary prophylaxis). Although the magnitude of the effects of pre-emptive stenosis correction was considerable for patient-centred outcomes, results were either heterogeneous or imprecise. While pre-emptive stenosis correction may reduce the rates of hospitalisation (IRR 0.54, 95% CI 0.31 to 0.93; I² = 67%; 4 study comparisons, 219 participants) and use of catheters (IRR 0.58, 95% CI 0.35 to 0.98; I² = 53%; 6 study comparisons, 394 participants), it may also increase the rates of diagnostic procedures (IRR 1.78, 95% CI 1.18 to 2.67; I² = 62%; 7 study comparisons, 539 participants), infection (IRR 1.74, 95% CI 0.78 to 3.91; I² = 0%; 3 studies, 248 participants) and mortality (RR 1.38, 95% CI 0.91 to 2.11; I² = 0%; 5 studies, 386 participants).In general, risk of bias was high or unclear in most studies for many domains we assessed. Four studies were published after 2005 and only one had evidence of registration within a trial registry. No study reported information on authorship and/or involvement of the study sponsor in data collection, analysis, and interpretation. AUTHORS' CONCLUSIONS: Pre-emptive correction of a newly identified or known stenosis in a functional AV access does not improve access longevity. Although pre-emptive stenosis correction may be promising in fistulas existing evidence is insufficient to guide clinical practice and health policy. While pre-emptive stenosis correction may reduce the risk of hospitalisation, this benefit is uncertain whereas there may be a substantial increase (i.e. 80%) in the use of access-related procedures and procedure-related adverse events (e.g. infection, mortality). The net effects of pre-emptive correction on harms and resource use are thus unclear.

The effect of citrate dialysate on intradialytic heparin dose in haemodialysis patients: study design of a randomised controlled trial.

BACKGROUND: Unfractionated heparin is the most common anticoagulant used in haemodialysis (HD), although it has many potential adverse effects. Citrate dialysate (CD) has an anticoagulant effect which may allow reduction in cumulative heparin dose (CHD) compared to standard acetate dialysate (AD). METHODS: This double-blinded, randomised, cross-over trial of chronic haemodialysis patients determines if CD allows reduction in CHD during HD compared with AD. After enrolment, intradialytic heparin is minimised during a two-week run-in period using a standardised protocol based on a visual clotting score. Patients still requiring intradialytic heparin after the run-in period are randomised to two weeks of HD with AD followed by two weeks of CD (Sequence 1) or two weeks of HD with CD followed by two weeks of AD (Sequence 2). The primary outcome is the change in CHD with CD compared with AD. Secondary outcomes include metabolic and haemodynamic parameters, and dialysis adequacy. DISCUSSION: This randomised controlled trial will determine the impact of CD compared with AD on CHD during HD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01466959.