Jennifer M. MacRae

Associations between Hemodialysis Access Type and Clinical Outcomes: A Systematic Review

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41-1.67), fatal infections (2.12, 1.79-2.52), and cardiovascular events (1.38, 1.24-1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25-1.52), fatal infections (1.49, 1.15-1.93), and cardiovascular events (1.26, 1.11-1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09-1.27) and fatal infection (1.36, 1.17-1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95-1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.

Central vein stenosis: a common problem in patients on hemodialysis.

Central vein stenosis (CVS) has been associated with subclavian (SCV) catheter insertions. The prevalence of CVS in the current era with minimal use of SCV catheters is unknown. Furthermore, the prevalence of CVS in patients with access problems has not been previously described to our knowledge. We evaluated 235 prevalent patients on hemodialysis (HD), and, of these, 133 underwent venography for access related concerns over a 14 month period. Of these 133 patients, 55 (41%) had evidence of significant CVS on venogram. Patients with CVS had a longer duration on HD (43 ± 12 months vs. 34 ± 15 months, p = 0.018) and a history of a previous HD catheter insertion (52/55 patients vs. 59/78 patients, p = 0.0039). There were only 18 patients with a subclavian catheter insertion. In those with any history of previous HD catheter insertion, multivariate analysis demonstrated that number of catheters remains a significant factor (OR 2.69, p = 0.0004) even after excluding those subclavian insertions. This study demonstrates that CVS occurs in almost half of the patients with access problems undergoing venography. We confirm the important contribution of central vein cannulation to CVS and show that, despite minimizing subclavian catheter insertion, CVS remains a relatively common occurrence. Thus further studies should attempt to determine the true incidence of this problem and ultimately address the optimal treatment strategies.

Overview of the Alberta Kidney Disease Network

BackgroundThe Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.DescriptionThe laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.ConclusionThe unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.

Meta-analysis: Antibiotics for Prophylaxis against Hemodialysis Catheter–Related Infections

Context Catheter-related infections are a major cause of illness among hemodialysis patients. Contribution This systematic review found 16 randomized trials that evaluated antibiotic prophylaxis for adults receiving long-term hemodialysis with a central venous catheter. The trials assessed the potential benefits of applying antibiotics topically to the catheter exit site or instilling them intraluminally into the catheter. Compared with no antibiotic therapy, prophylaxis with either topical or intraluminal antibiotics reduced bloodstream infections and the need for catheter removals. Caution Most trials were short in duration and were not blinded. Implication Topical or intraluminal antibiotic prophylaxis may reduce catheter-related bloodstream infections in hemodialysis patients. The Editors Although arteriovenous fistulas are the preferred vascular access for patients receiving long-term hemodialysis, central venous catheters remain a common form of access for many patients (1, 2). In North America, catheters are currently used in as many as 60% to 70% of incident and 30% to 40% of prevalent patients undergoing hemodialysis (1, 3). Catheter use is associated with increased patient morbidity and mortality, including a 10- to 20-fold greater risk for bacteremia than with fistulas (2). The resulting 0.16 to 0.66 catheter-related bloodstream infection that occurs for every 100 catheter-days may partly explain the 2- to 3-fold increased risk for death associated with catheter use among patients undergoing hemodialysis (2, 4, 5). Techniques to reduce catheter-related infection risk include strict adherence to sterile technique and use of chlorhexidine or povidoneiodine cleaning solutions with catheter care (2, 6, 7). Recent strategies to further reduce catheter-related infection rates include use of antibiotic ointments applied around the catheter exit site and antibiotics locked in the intraluminal portion of the catheter between dialysis sessions. However, many studies of these strategies are limited by small sample sizes and short follow-up, and some are published only in abstract form. In addition, because these interventions are not without risk or cost, the role of antibiotic prophylaxis for catheter-related infection remains unclear (8). To help clarify the role of these strategies, we reviewed randomized, controlled trials (RCTs) that assessed the efficacy of topical and intraluminal antibiotics for primary prophylaxis against catheter-related bloodstream infection in adult hemodialysis patients. Methods Data Sources and Searches Two reviewers searched MEDLINE (1966 through October 2007), EMBASE (1980 through October 2007), and Cochrane Central Register of Controlled Trials (1996 through October 2007) according to a standardized protocol by using the OVID search engine. We developed the following 3 comprehensive search themes by using text word and database-specific thesaurus terms: catheter-related bloodstream infection (searching for catheter-related bloodstream infection, bacteremia, or septicemia), dialysis (searching for renal dialysis), and catheter (searching for indwelling catheter, catheterization, central venous catheter, or hemodialysis catheter). We combined these themes by using the Boolean and operator. We used a filter described by Egger and colleagues (9) to limit our search to RCTs. We supplemented citations identified from electronic databases by reviewing the reference lists of all identified research and review articles, reviewing abstracts of the American Society of Nephrology Annual Meeting from 1999 to 2006, and searching clinical trial registries (www.clinicaltrials.gov, www.isrctn.org, www.csp.research.med.va.gov, and www.controlled-trials.com/mrct). Study Selection The 2 reviewers independently evaluated articles for eligibility in a 2-stage procedure. In the first stage, all identified abstracts were reviewed. In the second stage, we performed a full-text review of articles that met the inclusion criteria and articles for which there was uncertainty as to eligibility. Articles selected by either reviewer were reviewed by both reviewers in the second stage and evaluated for inclusion and exclusion criteria. Inclusion criteria were study design (RCT), study population (adults receiving long-term hemodialysis using a central venous catheter), intervention (use of an antibiotic applied topically to the catheter exit site or instilled intraluminally into the catheter), comparison (with another or no antimicrobial agent), and outcome (catheter-related bloodstream infection rate or secondary outcomes of interest). Both published and unpublished studies were eligible for inclusion regardless of language. We excluded studies in children and studies in which an antibiotic was used for treating an established line infection or for prophylaxis after a previous catheter-related bloodstream infection. Data Extraction and Quality Assessment We performed data extraction and reporting according to the recommendations of the QUORUM (Quality of Reporting of Meta-analyses) statement (10). Both reviewers independently extracted data from all primary studies that fulfilled the inclusion criteria; disagreement was resolved by consensus. The primary outcome was rate of catheter-related bloodstream infection by any organism, commonly defined as a positive blood culture in a febrile, catheter-dependent patient in the absence of alternative sources of infection on clinical evaluation. The secondary outcomes were rates of Staphylococcus aureus, catheter-related bloodstream infection, catheter exit-site infection, catheter removal secondary to complications, hospitalization for infection, death, adverse events, or isolation of antimicrobial-resistant organisms. The 2 reviewers independently scored the methodological quality of the studies, including the Jadad score (11). Allocation concealment was considered adequate if the study used an off-site or independent source to assign treatment or used opaque, sealed envelopes for assignment. We contacted authors of studies published only in abstract form to obtain additional study information and confirm final results. Statistical Analysis We summarized outcomes from trials by using rate ratios (number of events per 100 catheter-days in the prophylaxis group vs. the control group) to best account for studies with more than 1 infection per patient, as well as the varying follow-ups between groups. For studies in which 1 group contained no events, we approximated rate ratios by adding 0.05 to each group of the trial (9). Because of the differences in antimicrobial application site, we analyzed results for topical and intraluminal antibiotic agents separately. We further stratified studies by individual antibiotic in secondary analyses. We used fixed-effects models created by using the inverse variance method to produce pooled rate ratios with 95% CIs for study outcomes in the primary analysis (9). We performed sensitivity analyses by using risk ratios (number of events per patient in the prophylaxis group vs. the control group) as the measure of effect, counting the first infectious event per patient, in fixed-effects models of Mantel and Haenszel (9). Similarly, we analyzed mortality outcomes by using risk ratios. We evaluated the presence of heterogeneity across trials by using the I 2 statistic, which quantifies the percentage of variability that can be attributed to between-study differences (12). Because we found no significant heterogeneity, we did not perform random-effects analyses. We also tested for publication bias by using funnel plots, the Begg test for asymmetry, and an Egger test for trials of intraluminal antibiotics (9). We did not test for publication bias for trials of topical antimicrobial agents because of the small number of these studies. All statistical analyses were performed by using Stata, version 9.2 (Stata, College Station, Texas). Results Identification of Studies Figure 1 summarizes the progress through the stages of the systematic review. Of 158 unique citations, we excluded 120 on initial screening, leaving 38 articles for full-text review. We identified duplicate publications (13) of 3 studies; 2 were full reports of RCTs previously published as abstracts, whereas 1 (14) overlapped with a separately published study (15). Of the 16 articles that met inclusion criteria for the systematic review, 13 were published in peer-reviewed journals and 3 were published in abstract form only. Both reviewers agreed on the studies selected for meta-analysis and their validity assessments. Figure 1. Study flow diagram. Study Characteristics Table 1 shows the details of the trials that met our inclusion criteria. A total of 1395 participants were included from 16 trials. We identified 5 trials of topical antibiotics comprising 630 patients who were followed for a total of 45929 catheter-days (1620). Three trials (1618), comprising 360 participants, compared mupirocin ointment with no antibiotic prophylaxis, whereas 1 trial (20) compared polysporin triple-antibiotic ointment with no prophylaxis. One trial (19) compared mupirocin ointment with Medihoney (Medihoney Pty, Brisbane, Australia), an irradiated antibacterial honey. This was the only study in which both study groups included an antimicrobial agent, and we could therefore not include it in the meta-analysis comparing antibiotic prophylaxis with no prophylaxis. We identified 11 trials that compared intraluminal antibiotics with a strategy consisting of no antibiotic prophylaxis, comprising 765 patients followed for a total of 100167 catheter-days (15, 2130). The interventions consisted of gentamicin in 6 trials (2124, 27, 28) comprising 347 participants, minocycline in 2 trials (25, 26, 28) comprising 102 participants, taurolidine in 1 trial (25), cefazolin and gentamicin in 1 trial (29), cefotaxime in 1 trial (15), and vancomycin and gentamicin in 1 trial (30). Nori and colleagues (28) used 2

Suboptimal initiation of dialysis with and without early referral to a nephrologist

BACKGROUND Our objective was to examine patients who initiate renal replacement therapy (RRT) at 10 representative Canadian centers, characterize their initiation as inpatient or outpatient and describe their initial type of dialysis access, duration of pre-dialysis care and clinical status at the time of dialysis initiation. We also examined the impact of an optimal dialysis start (i.e. initiated as an outpatient with an arteriovenous fistula, arteriovenous graft or peritoneal dialysis catheter) on subsequent health outcomes. METHODS Charts of consecutive incident RRT patients were identified from 1 July to 31 December 2006. Information was collected until 6 months after the initiation or until death, transplant or transfer. RESULTS Three hundred and thirty-nine incident RRT patients were studied: 39.6% initiated as an inpatient; 54% started hemodialysis (HD) with a central venous catheter; 15.3% had <1 month predialysis care, while 64.6% had >1 year. Optimal starts occurred in 39.5% of patients. For HD patients, optimal starts occurred in 19.8%. Suboptimal starts were noted in patients referred <12 months prior to end-stage renal disease (44%) and in patients referred earlier (56%). The composite end point of death, transfusion or subsequent hospitalization was significantly reduced with an optimal start [hazard ratio 0.47 (95% confidence interval 0.32-0.68), P = 0.0001]. CONCLUSIONS Suboptimal initiation of dialysis is common in patients referred early or late. The benefits of early referral are lost if dialysis is initiated suboptimally. There is a need to identify factors that lead to suboptimal initiation despite early referral.

A Randomized Trial Comparing Buttonhole with Rope Ladder Needling in Conventional Hemodialysis Patients

BACKGROUND AND OBJECTIVES Buttonhole needling is reported to be associated with less pain than standard needling. The purpose of this study was to compare patient perceived pain and fistula complications in buttonhole and standard needling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this study, 140 conventional hemodialysis patients were randomly assigned to buttonhole or standard needling. The primary outcome was patient perceived pain with needling at 8 weeks. Fistula complications of hematoma, bleeding postdialysis, and infection were tracked. RESULTS Median pain score at 8 weeks using a visual analog scale from 0 to 10 cm was similar for standard and buttonhole needling (1.2 [0.4-2.4] versus 1.5 [0.5-3.4]; P=0.57). Rate of hematoma formation in standard needling was higher (436 versus 295 of 1000 hemodialysis sessions; P=0.03). Rate of no bleeding postdialysis was 23.6 and 28.3 per 1000 in standard and buttonhole needling, respectively (P=0.40). Rate of localized signs of infection in standard versus buttonhole needling was 22.4 versus 50 per 1000 (P=0.003). There was one episode of Staphylococcal aureus bacteremia during the 8 weeks with buttonhole needling and no episodes with standard needling (P=1.00). Within 12 months of follow-up, another two buttonhole needling episodes developed S. aureus bacteremia, and nine buttonhole needling episodes had needling site abscesses requiring intravenous antibiotics versus zero standard needling episodes (P=0.003). CONCLUSIONS Patients had no difference in pain between buttonhole and standard needling. Although fewer buttonhole needling patients developed a hematoma, there was an increased risk of bacteremia and localized signs of infection. Routine use of buttonhole needling is associated with increased infection risk.

Citrate 4% versus Heparin and the Reduction of Thrombosis Study (CHARTS)

BACKGROUND AND OBJECTIVES Citrate 4% has antithrombotic and antibacterial properties, which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Sixty-one prevalent hemodialysis (HD) patients dialyzing with a tunneled cuffed HD catheter were randomized in a pilot study to receive either heparin 5000 U/ml or citrate 4% as a locking agent after HD. The primary outcomes were the development of catheter dysfunction (defined as a blood pump speed <250 ml/min or the use of tissue plasminogen activator) and catheter-associated bacteremia. The secondary outcomes were the development of an exit-site infection or bleeding complications (either local or systemic). RESULTS Citrate had comparable catheter dysfunction episodes to heparin (13/32 [41%] cases versus 12/29 [41%] cases, respectively). There were no differences in the development of catheter-associated bacteremia (2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group; P = 0.607) or exit-site infection (2.2/1000 catheter days for both groups). CONCLUSIONS The preliminary findings from our pilot study demonstrate that 4% citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections. Because citrate is significantly cheaper and has a more favorable side effect profile than heparin, it can be considered a potentially better locking agent in HD catheters.

Wave-intensity analysis: a new approach to left ventricular filling dynamics

SummaryIn order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks.Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to “diastolic suction”.Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase.Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration.Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction.Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.

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.

Oral estrogen therapy in postmenopausal women is associated with loss of kidney function

Women are generally protected against progressive loss of kidney function; however, this advantage seems to diminish with menopause. Because of conflicting reports on the association between use of hormone therapy and kidney function we studied 5845 women (1459 on hormone therapy and 4386 non-users) who were over 66 years of age and had at least 2 serum creatinine measurements during the 2 year study period. After adjustment for covariates, hormone use (estrogen-only, progestin-only, or both) was associated with a significant loss of estimated GFR as the primary outcome along with an increased risk of rapid loss of kidney function as the secondary outcome compared to non-users. This increased rate of loss was associated with oral but not transvaginal estrogen use. An increased cumulative dose of estrogen was also associated with a greater decline in estimated GFR. Our study shows an independent association in a dose-dependent manner of estrogen use and loss of kidney function in this elderly population.