Louise Moist

Guidelines for the management of chronic kidney disease

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

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 Vascular Access Modifies the Association between Dialysis Modality and Survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

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.).

Volume control and blood pressure management in patients undergoing quotidian hemodialysis

BACKGROUND Hypertension and interdialytic weight gain are associated with left ventricular hypertrophy (LVH), an important predictor of cardiovascular mortality in hemodialysis (HD) patients. METHODS In the London Daily/Nocturnal Hemodialysis Study, a group of patients receiving quotidian HD, either short daily (n = 11) or long nocturnal (n = 12), were followed for up to 18 months. Patients were assessed for effects of quotidian HD therapy on blood pressure, interdialytic weight gain, extracellular fluid volume (ECFV), intensity of antihypertensive therapy, and homocysteine levels. RESULTS Significant reductions in predialysis mean arterial blood pressure were observed in the daily HD group at 6 months (P < 0.04) and in the nocturnal HD group at 9 months (P < 0.03); these improvements persisted throughout the study period. The daily HD group had a 60% reduction in mean number of antihypertensive tablets per day at 1 month and an 8.8-fold reduction by 18 months. Nocturnal HD patients experienced a 3.3-fold reduction, and control patients, a 1.4-fold increase in mean number of tablets per day by 18 months. By 3 months, the daily HD group showed a significant decrease in interdialytic weight gain (P < 0.0005) and lower ECFV than controls (P < 0.05). The nocturnal HD group had a transient, but significant, increase in interdialytic weight gain at 6 and 15 months (P < 0.05) and no difference in ECFV compared with controls, suggesting a different mechanism of blood pressure control. Homocysteine levels were significantly lower for both quotidian HD groups compared with conventional HD patients. CONCLUSION Quotidian HD is a promising therapy with potent antihypertensive effects, resulting in improved blood pressure control. This, together with improved homocysteine levels, may be beneficial in the long term with regard to cardiovascular mortality.

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.

Urine Volume and Change in Estimated GFR in a Community-Based Cohort Study

BACKGROUND AND OBJECTIVES The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at study entry. Percentage annual change in eGFR from baseline was categorized as average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or ≥5% (rapid decline). RESULTS 2148 participants provided valid 24-hour urine samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and ≥3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m(2), respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume ≥3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease. CONCLUSIONS In this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume.

Association between estimated glomerular filtration rate at initiation of dialysis and mortality

Background Recent studies have reported a trend toward earlier initiation of dialysis (i.e., at higher levels of glomerular filtration rate) and an association between early initiation and increased risk of death. We examined trends in initiation of hemodialysis within Canada and compared the risk of death between patients with early and late initiation of dialysis. Methods The analytic cohort consisted of 25 910 patients at least 18 years of age who initiated hemodialysis, as identified from the Canadian Organ Replacement Register (2001–2007). We defined the initiation of dialysis as early if the estimated glomerular filtration rate was greater than 10.5 mL/min per 1.73 m2. We fitted time-dependent proportional-hazards Cox models to compare the risk of death between patients with early and late initiation of dialysis. Results Between 2001 and 2007, mean estimated glomerular filtration rate at initiation of dialysis increased from 9.3 (standard deviation [SD] 5.2) to 10.2 (SD 7.1) (p < 0.001), and the proportion of early starts rose from 28% (95% confidence interval [CI] 27%–30%) to 36% (95% CI 34%–37%). Mean glomerular filtration rate was 15.5 (SD 7.7) mL/min per 1.73 m2 among those with early initiation and 7.1 (SD 2.0) mL/min per 1.73 m2 among those with late initiation. The unadjusted hazard ratio (HR) for mortality with early relative to late initiation was 1.48 (95% CI 1.43–1.54). The HR decreased to 1.18 (95% CI 1.13–1.23) after adjustment for demographic characteristics, serum albumin, primary cause of end-stage renal disease, vascular access type, comorbidities, late referral and transplant status. The mortality differential between early and late initiation per 1000 patient-years narrowed after one year of follow-up, but never crossed and began widening again after 24 months of follow-up. The differences were significant at 6, 12, 30 and 36 months. Interpretation In Canada, dialysis is being initiated at increasingly higher levels of glomerular filtration rate. A higher glomerular filtration rate at initiation of dialysis is associated with an increased risk of death that is not fully explained by differences in baseline characteristics.

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.