Charmaine E. Lok

Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.

BACKGROUND Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease. METHODS We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model. FINDINGS Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98). INTERPRETATION Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder. FUNDING None.

Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis.

BACKGROUND Advantages of the arteriovenous fistula (AVF), including long patency and few complications, were ascertained more than 2 decades ago and may not apply to the contemporary dialysis population. STUDY DESIGN Systematic review and meta-analysis. Estimates were pooled using a random-effects model and sources of heterogeneity were explored using metaregression. SETTING & POPULATION Patients treated with long-term hemodialysis using an AVF. SELECTION CRITERIA FOR STUDIES English-language studies indexed in MEDLINE between 2000 and 2012 using prospectively collected data on 100 or more AVFs. PREDICTOR Age, AVF location, and study location. OUTCOMES Outcomes of interest were primary AVF failure and primary and secondary patency at 1 and 2 years. RESULTS 7,011 citations were screened and 46 articles met eligibility criteria (62 unique cohorts; n = 12,383). The rate of primary failure was 23% (95% CI, 18%-28%; 37 cohorts; 7,393 AVFs). When primary failures were included, the primary patency rate was 60% (95% CI, 56%-64%; 13 studies; 21 cohorts; 4,111 AVFs) at 1 year and 51% (95% CI, 44%-58%; 7 studies; 12 cohorts; 2,694 AVFs) at 2 years. The secondary patency rate was 71% (95% CI, 64%-78%; 10 studies; 11 cohorts; 3,558 AVFs) at 1 year and 64% (95% CI, 56%-73%; 6 studies; 11 cohorts; 1,939 AVFs) at 2 years. In metaregression, there was a significant decrease in primary patency rate in studies that started recruitment in more recent years. LIMITATIONS Low quality of studies, variable clinical settings, and variable definitions of primary AVF failure. CONCLUSIONS In recent years, AVFs had a high rate of primary failure and low to moderate primary and secondary patency rates. Consideration of these outcomes is required when choosing a patients preferred access type.

Hemodialysis Infection Prevention with Polysporin Ointment

Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter. In such patients, catheter-related infections are a common and serious complication. This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections. A total of 169 patients receiving hemodialysis through a central venous catheter were randomized to receive Polysporin Triple or placebo using a double-blind study design. In the 6-mo study period, infections were observed in more patients in the placebo group than in the Polysporin Triple group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004) were also greater in the placebo group. Within the 6-mo study period, there were 13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple group (P = 0.0041). When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died. The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients.

Prevention of Dialysis Catheter Malfunction with Recombinant Tissue Plasminogen Activator

BACKGROUND The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown. METHODS We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel. RESULTS A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups. CONCLUSIONS The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Current Controlled Trials number, ISRCTN35253449.).

Increased Hemodialysis Catheter Use in Canada and Associated Mortality Risk: Data from the Canadian Organ Replacement Registry 2001–2004

BACKGROUND AND OBJECTIVES The 1999 Canadian vascular access guidelines recommend the fistula as the access of choice. The study describes the trends in hemodialysis access use, variation among provinces, and the association with mortality from 2001 to 2004. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS An observational study of adult patients registered in Canadian Organ Replacement Registry on hemodialysis. Access trends were examined among incident and prevalent hemodialysis patients adjusted for age, sex, body mass index, late referral, race, smoking status, province, etiology of end-stage renal disease, and comorbidities. Cox proportional hazard regression analysis was used to analyze risk for death for patients followed to December 31, 2005. RESULTS From 2001 to 2004, incident catheter use increased from 76.8% to 79.1%, fistulas decreased from 21.6% to 18.6%, and grafts remained between 2.1% to 2.6%. Prevalent catheter use increased from 41.8% to 51.7%, and fistulas and grafts decreased from 46.8% to 41.6% and 11.4% to 6.7%, respectively. There was significant variation in incident and prevalent fistulae use among the provinces. Adjustment for differences in patient characteristics did not change these trends. Incident catheter use was associated with a 6 times greater risk of death compared with fistula or graft use combined. CONCLUSIONS In Canada there has been a decrease in fistulae and grafts with a subsequent increase in catheters that is not explained by changes in patient characteristics. Vascular access use varied by province, suggesting differences in practice patterns. Because incident catheter use was associated with increased mortality, urgent measures are needed to develop strategies to decrease catheter use.

Prevention and management of catheter-related infection in hemodialysis patients

Central venous catheter-related infections have been associated with high morbidity, mortality, and costs. Catheter use in chronic hemodialysis patients has been recognized as distinct from other patient populations who require central venous access, leading to recent adaptations in guidelines-recommended diagnosis for catheter-related bacteremia (CRB). This review will discuss the epidemiology and pathogenesis of hemodialysis CRB, in addition to a focus on interventions that have favorably affected CRB outcomes. These include: (1) the use of prophylactic topical antimicrobial ointments at the catheter exit site, (2) the use of prophylactic catheter locking solutions for the prevention of CRB, (3) strategies for management of the catheter in CRB, and (4) the use of vascular access managers and quality initiative programs.

Late Creation of Vascular Access for Hemodialysis and Increased Risk of Sepsis

The creation of fistulas or grafts before starting dialysis is recommended, but whether it reduces major adverse events is largely unknown. The objective of this study was to determine if early access creation was associated with a reduced risk of hospitalization from sepsis and mortality. Fistulas or grafts created at least 4 mo before starting hemodialysis were defined as Early creations (n = 1240), and accesses created between 4 mo and 1 mo before starting hemodialysis were defined as Just Prior creations (n = 997). Accesses created within 1 mo of starting dialysis or after were defined as Late creations (reference group, n = 3687). Hemodialysis catheter use was defined as insertion, removal, or manipulation of a catheter before the occurrence of sepsis. Eighty percent of accesses were fistulas. Early access creation was associated with a relative risk (RR) of sepsis of 0.57 (95% CI, 0.41 to 0.79) compared with Late access creation. Catheter use increased the risk of sepsis by 1.41 (95% CI, 1.14 to 1.81). The risk of sepsis with Early creation decreased to 0.48 (95% CI, 0.35 to 0.65) if catheter use was not adjusted. Early access creation was associated with lower mortality (RR 0.76; 95% CI 0.58 to 1.00), but this association became nonsignificant if catheter use and sepsis were adjusted. Catheter use and sepsis independently increased mortality. This study demonstrates that fistula creation at least 4 mo before starting chronic hemodialysis is associated the lowest risk of sepsis and death, primarily by reducing the use of hemodialysis catheters.

Standardized Definitions for Hemodialysis Vascular Access

Vascular access dysfunction is one of the leading causes of morbidity and mortality among end‐stage renal disease patients. Vascular access dysfunction exists in all three types of available accesses: arteriovenous fistulas, arteriovenous grafts, and tunneled catheters. To improve clinical research and outcomes in hemodialysis (HD) access dysfunction, the development of a multidisciplinary network of collaborative investigators with various areas of expertise, and common standards for terminology and classification in all vascular access types, is required. The North American Vascular Access Consortium (NAVAC) is a newly formed multidisciplinary and multicenter network of experts in the area of HD vascular access, who include nephrologists and interventional nephrologists from the United States and Canada with: (1) a primary clinical and research focus in HD vascular access dysfunction, (2) national and internationally recognized experts in vascular access, and (3) a history of productivity measured by peer‐reviewed publications and funding among members of this consortium. The consortium’s mission is to improve the quality and efficiency in vascular access research, and impact the research in the area of HD vascular access by conducting observational studies and randomized controlled trials. The purpose of the consortium’s initial manuscript is to provide working and standard vascular access definitions relating to (1) epidemiology, (2) vascular access function, (3) vascular access patency, and (4) complications in vascular accesses relating to each of the vascular access types.

The effects of calcium-based versus non-calcium-based phosphate binders on mortality among patients with chronic kidney disease: a meta-analysis

BACKGROUND The effects of calcium compared with non-calcium-based phosphate binders on mortality, cardiovascular events and vascular calcification in patients with chronic kidney disease (CKD) are unknown. METHODS To address this question, we conducted a systematic review. We electronically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. We identified 160 potential studies and included 8 randomized trials. Eligible studies, determined by consensus using predefined criteria, were reviewed, and data were extracted onto a standard from. RESULTS There was a trend towards a decrease in all-cause mortality among non-calcium-based versus calcium-based phosphate binders [relative risk (RR) 0.68; 95% CI 0.41-1.11] based upon eight randomized controlled trials and 2873 subjects. Two trials reported on cardiovascular events with a RR of 0.85 (95% CI 0.35-2.03) in patients receiving calcium-based versus non-calcium-based binders. Coronary artery calcification was reported in five trials involving 469 patients; the difference in the change in the calcium score from baseline to follow-up among subjects taking non-calcium-based binders versus calcium-based binders was -76.35 (95% CI -158.25-5.55). CONCLUSION Despite the trends observed, we did not find a statistically significant difference in cardiovascular mortality and coronary artery calcification in patients receiving calcium-based phosphate binders compared to non-calcium-based phosphate binders. However, the data are limited by the small number of studies and the confidence intervals do not exclude a potentially important beneficial effect. Therefore, further randomized trials are required.

The three-year incidence of fracture in chronic kidney disease

Knowing a persons fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2)), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.