Charmaine Lok

Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

Biomarkers of inflammation, fibrosis, cardiac stretch and injury predict death but not renal replacement therapy at 1 year in a Canadian chronic kidney disease cohort

BACKGROUND Newer biomarkers, reflective of biological processes, such as inflammation and fibrosis, cardiac stretch or damage and vascular health may be useful in understanding clinical events in chronic kidney disease (CKD). We assessed whether these newer biomarkers, alone or as a panel, improve risk prediction for renal replacement therapy or death, over and above conventional clinical, demographic and laboratory variables. METHODS We conducted a prospective observational Canadian cohort study in 2544 CKD patients with estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.73 m(2), under nephrology care, in urban and rural centers. We measured traditional clinical and laboratory risk factors, as well as newer biomarkers: cystatin C, high sensitivity c-reactive protein (hsCRP), interleukin 6 (IL6), transforming growth factor β1 (TGFβ1), fibroblast growth factor 23 (FGF23), N-terminal probrain natriuretic peptide (NT-proBNP), troponin I and asymmetric dimethylarginine (ADMA). Key outcomes were renal replacement therapy (RRT, dialysis or transplantation) and death, during the first year follow-up after enrollment: a time point important for clinical decision-making for patients and providers. RESULTS Newer biomarkers do not improve the prediction of RRT, when added to conventional risk factors such as eGFR, urine albumin to creatinine ratio, hemoglobin, phosphate and albumin. However, in predicting death within 1 year, cystatin C, NT-proBNP, hsCRP and FGF23 values significantly improved model discrimination and reclassification: c statistic increased by absolute 4.3% and Net Reclassification Improvement for categories of low, intermediate and high risk at 11.2%. CONCLUSIONS Our findings suggest that the addition of newer biomarkers may be useful in predicting death in patients with established CKD within a 1-year timeframe. This information may be useful in informing prognosis and redirect resources to serve patients at higher risk to improve outcomes and sustainability of the nephrology care system.

Minimizing Hemodialysis Catheter Dysfunction: An Ounce of Prevention

The maintenance of tunneled catheter (TC) patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient.

An Economic Evaluation of rt-PA Locking Solution in Dialysis Catheters

In a recent randomized trial, weekly recombinant tissue plasminogen activator (rt-PA), 1 mg per lumen, once per week, and twice-weekly heparin as a locking solution (rt-PA/heparin) resulted in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin (heparin alone). We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs, including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial. Nonparametric bootstrap estimates were used to derive 95% confidence intervals (CIs) and mean cost differences between the treatment groups. The cost of the locking solution was higher in patients receiving rt-PA/heparin, but this was partially offset by lower costs for managing complications. Overall, the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449].

323 (95% CI, -

Risk factors for yeast superinfection in the treatment of suspected exit site infections: a case-control study

935 to

Comparison of post-creation procedures and costs between surgical and an endovascular approach to arteriovenous fistula creation.

1581; P=0.62). When the costs were extrapolated over a 1-year time horizon using decision analysis, assuming ongoing rt-PA effectiveness, the overall costs of the strategies were similar. This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia, and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term. In summary, we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin. Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA.

Hemodialysis Tunneled Catheter-Related Infections

BackgroundMany patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction.Methods/DesignThe study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin.DiscussionResults from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions.

Arteriovenous Access Infection, Neuropathy, and Other Complications

PURPOSE The risk of infection can be reduced in hemodialysis (HD) patients with central venous catheters (CVCs) by using prophylactic intranasal mupirocin or polysporin at the exit site. However, there are concerns about the potential emergence of resistant microorganisms. The purpose of our study was to determine if the use of polysporin double in the treatment of exit site infections was associated with the emergence of yeast positive exit site cultures. METHODS In this case control study, we evaluated the risk of developing yeast positive exit site cultures after introducing a polysporin medical directive for the treatment of presumed exit site infections in our HD units. All HD patients using a CVC for blood access at the Ottawa Hospital were eligible for study. Demographic variables, use of polysporin, antibiotics and immunosuppressive medications were compared between those patients with yeast positive exit site cultures and controls. RESULTS There was no differences in age, gender or diabetic status between the cases and controls. However, the use of polysporin, antibiotics and immunocompromised status were associated with an increased risk of yeast positive exit site cultures. The relative importance of each of these factors could not be determined using this study design and requires future prospective study. CONCLUSIONS The emergence of yeast positive exit site cultures after the introduction of a new medical directive at a tertiary care hospital highlights the difference between medications used for prophylaxis and those used for treatment of CVC infections in high risk dialysis patients.

Practical Aspects of Nontunneled and Tunneled Hemodialysis Catheters

Introduction Due to early and late failures that may occur with surgically created hemodialysis arteriovenous fistulas (SAVF), post-creation procedures are commonly required to facilitate AVF maturation and maintain patency. This study compared AVF post-creation procedures and their associated costs in patients with SAVF to patients with a new endovascularly created AVF (endoAVF). Methods A 5% random sample from Medicare Standard Analytical Files was abstracted to determine post- creation procedures and associated costs for SAVF created from 2011 to 2013. Medicare enrollment during the 6 months prior to and after the AVF creation was required. Patients’ follow-up inpatient, outpatient, and physician claims were used to identify post-creation procedures and to estimate average procedure costs. Comparative procedural information on endoAVF was obtained from the Novel Endovascular Access Trial (NEAT). Results Of 3764 Medicare SAVF patients, 60 successfully matched to endoAVF patients using 1:1 propensity score matching of baseline demographic and clinical characteristics. The total post-creation procedural event rate within 1 year was lower for endoAVF patients (0.59 per patient-year) compared to the matched SAVF cohort (3.43 per patient-year; p<0.05). In the endoAVF cohort, event rates of angioplasty, thrombectomy, revision, catheter placement, subsequent arteriovenous graft (AVG), new SAVF, and vascular access-related infection were all significantly lower than in the SAVF cohort. The average first year cost per patient-year associated with post-creation procedures was estimated at US