Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Reporting of the estimated glomerular filtration rate was associated with increased use of angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers in CKD.

Many guidelines suggest that angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists (collectively referred to as renin, angiotensin, aldosterone system blockers (RAAS blockers)) are the preferred treatment for hypertension in most patients with chronic kidney disease (CKD). Improving the recognition of CKD with the introduction of eGFR reporting was intended to have more patients recognized with and treated for this disease. To quantify this, we examined trends in RAAS-blocker use over an 88-month period before and after routine eGFR reporting in southwestern Ontario, Canada. An intervention analysis with seasonal time-series modeling on linked health administrative data for 45,361 ambulatory residents with CKD (eGFR stages 3-5) older than 65 years was performed with a primary outcome of RAAS-blocker usage. The reporting of eGFR was associated with a significant increase in the use of RAAS blockers, as the prescription rate was 571 per 1000 patients with CKD prior to reporting but improved to 607 per 1000 after reporting. There was a significant increase in RAAS-blocker use attributable to eGFR reporting of 19 per 1000 CKD patients. Since about 8% of the adult population has CKD, this equates to about 15,200 new patients receiving RAAS-blocker treatment by 1 year after the introduction of eGFR reporting in community laboratories. Thus, eGFR reporting contributes to improved, guideline-appropriate care of older patients with CKD.

Accounting for Age in the Definition of Chronic Kidney Disease.

Importance: Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease. Objective: To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold. Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m2 for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020. Exposures: A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m2 for age younger than 40, 40 to 64, and 65 years or older, respectively. Main Outcomes and Measures: Competing risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m2 for >3 months) and death without kidney failure. Results: The fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m2 with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively. Conclusions and Relevance: This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.

Progression and Regression of Chronic Kidney Disease by Age Among Adults in a Population-Based Cohort in Alberta, Canada.

Importance: The burden of chronic kidney disease (CKD) is expected to increase worldwide as the global population ages, potentially increasing the demand for nephrology services. Understanding whether CKD inevitably progresses or may regress can inform clinical decision-making and health policy. Objective: To study CKD progression and regression by age in adults with CKD. Design, Setting, and Participants: This population-based cohort study used linked administrative and laboratory data to assess adults in the province of Alberta, Canada, with incident mild, moderate, or severe CKD, defined by estimated glomerular filtration rate (eGFR) of 45 to 59, 30 to 44, or 15 to 29 mL/min/1.73 m2 for longer than 3 months, from April 1, 2009, to March 31, 2015. Data were analyzed from July 20 to November 30, 2020. Exposures: Age. Main Outcomes and Measures: Time to the earliest of CKD regression or progression (defined as sustained increase or drop in eGFR category for >3 months, respectively, and a ≥25% increase or decrease in eGFR from baseline, respectively), kidney failure (the earlier of kidney replacement initiation or eGFR <15 mL/min/1.73 m2 for >3 months), death, or censoring (outmigration, 5 years of follow-up, or end of study on March 31, 2017). Results: Study participants with CKD (55.2% women and 44.8% men) included 81 320 with mild CKD (mean [SD] age, 72.4 [11.3] years), 35 929 with moderate CKD (mean [SD] age, 77.1 [11.5] years), and 12 237 with severe CKD (mean [SD] age, 76.6 [13.8] years). The annual incidence of CKD increased with advancing age, from 180 per 100 000 population younger than 65 years to 7250 per 100 000 in those 85 years or older. After cohort entry, the 5-year probability of regression was similar to that of progression or kidney failure in mild (14.3% vs 14.6%), moderate (18.9% vs 16.5%), and severe (19.3% vs 20.4%) CKD. As mortality at 5 years increased with advancing age in moderate (from 9.6% for age <65 years to 48.4% for age ≥85 years) and severe (from 10.8% for age <65 years to 60.2% for age ≥85 years) CKD, the risk of progression or kidney failure decreased substantially (for moderate CKD, from 32.3% for <65 years to 9.4% for ≥85 years; for severe CKD, from 55.2% for <65 years to 4.7% for ≥85 years), whereas the probabilities of regression varied to a lesser extent (for moderate CKD, from 22.5% for <65 years to 15.4% for ≥85 years; for severe CKD, from 13.9% for <65 years to 18.7% for ≥85 years). Conclusions and Relevance: This cohort study found that with advancing age, CKD regression and death were more likely than CKD progression or kidney failure. These findings have important implications for patient care and for assessing the potential effect of population aging on the burden of CKD.

Sex differences in the vascular access of hemodialysis patients: a cohort study.

BACKGROUND: We describe differences for probability of receiving a fistula attempt, achieving fistula use, remaining catheter-free and the rate of access-related procedures as a function of sex. METHODS: Prospectively collected vascular access data on incident dialysis patients from five Canadian programs using the Dialysis Measurement Analysis and Reporting System to determine differences in fistula-related outcomes between women and men. The probability of receiving a fistula attempt and the probability of fistula use were determined using binary logistic regression. Catheter and fistula procedure rates were described using Poisson regression. We studied time to fistula attempt and time to fistula use, accounting for competing risks. RESULTS: We included 1446 (61%) men and 929 (39%) women. Men had a lower body mass index (P < 0.001) and were more likely to have coronary artery disease (P < 0.001) and peripheral vascular disease (p < 0.001). A total of 688 (48%) men and 403 (43%) women received a fistula attempt. Women were less likely to receive a fistula attempt by 6 months {odds ratio [OR] 0.64 [95% confidence interval (CI) 0.52-0.79]} and to achieve catheter-free use of their fistula by 1 year [OR 0.38 (95% CI 0.27-0.53)]. At an average of 2.30 access procedures per person-year, there is no difference between women and men [incidence rate ratio (IRR) 0.97 (95% CI 0.87-1.07)]. Restricting to those with a fistula attempt, women received more procedures [IRR 1.16 (95% CI 1.04-1.30)] attributed to increased catheter procedures [IRR 1.50 (95% CI 1.27-1.78)]. There was no difference in fistula procedures [IRR women versus men 0.96 (95% CI 0.85-1.07)]. CONCLUSION: Compared with men, fewer women undergo a fistula attempt. This disparity increases after adjusting for comorbidities. Women have the same number of fistula procedures as men but are less likely to successfully use their fistula.

When laboratories report estimated glomerular filtration rates in addition to serum creatinines, nephrology consults increase.

Serum creatinine alone can be difficult to interpret as a measure of kidney function such that chronic kidney disease might be under-recognized in the general population. In the province of Ontario, Canada, all outpatient laboratories now report estimated glomerular filtration rate (eGFR) in addition to serum creatinine. To determine the impact of this reporting on clinical practice, we linked health administrative data for more than 8 million adults of age 25 years or older over an almost 10-year period and conducted a population-based intervention analysis with seasonal time-series modeling to determine overall trends in the number and type of patients seen by nephrologists. Compared to the period when only serum creatinines were reported, the number of patients seen in consultation by nephrologists increased after eGFR reporting by an average of 24% (an absolute increase of 2.9 consults per 100,000 adults), an increase of about 23 consults per nephrologist per year. The greatest increases were seen in women (39% increase) and those 80 years of age and older (58% increase). Our study found that eGFR reporting was associated with a sudden increase in the number of nephrology consults. However, it remains to be seen whether the routine reporting of eGFR results in improved treatment and outcomes for those with chronic kidney disease.

Catheter Insertion and Perioperative Practices Within the ISPD North American Research Consortium.

UNLABELLED: ♦ BACKGROUND: In general, efforts to standardize care based on group consensus practice guidelines have resulted in lower morbidity and mortality. Although there are published guidelines regarding insertion and perioperative management of peritoneal dialysis (PD) catheters, variation in practice patterns between centers may exist. The objective of this study is to understand variation in PD catheter insertion practices in preparation for conducting future studies. ♦ METHODS: An electronic survey was developed by the research committee of the International Society for Peritoneal Dialysis - North American Research Consortium (ISPD-NARC) to be completed by physicians and nurses involved in PD programs across North America. It consisted of 45 questions related to 1) organizational characteristics; 2) PD catheter insertion practices; 3) current quality-improvement initiatives; and 4) interest in participation in PD studies. Invitation to participate in the survey was given to nephrologists and nurses in centers across Canada and the United States (US) identified by participation in the inaugural meeting of the ISPD-NARC. Descriptive statistics were applied to analyze the data. ♦ RESULTS: Fifty-one ISPD-NARC sites were identified (45% in Canada and 55% in the US) of which 42 responded (82%). Center size varied significantly, with prevalent PD population ranging from 6 - 300 (median: 60) and incident PD patients in the year prior to survey administration ranging from 3 - 180 (median: 20). The majority of centers placed fewer than 19 PD catheters/year, with a range of 0 - 50. Availability of insertion techniques varied significantly, with 83% of centers employing more than 1 insertion technique. Seventy-one percent performed laparoscopic insertion with advanced techniques (omentectomy, omentopexy, and lysis of adhesions), 62% of sites performed open surgical dissection, 10% performed blind insertion via trocar, and 29% performed blind placement with the Seldinger technique. Use of double-cuff catheters was nearly universal, with a near even distribution of catheters with pre-formed bend versus straight inter-cuff segments. There was also variation in the choice of perioperative antibiotics and perioperative flushing practices. Although 86% of centers had quality-improvement initiatives, there was little consensus as to appropriate targets. ♦ CONCLUSIONS: There is marked variability in PD catheter insertion techniques and perioperative management. Large multicenter studies are needed to determine associations between these practices and catheter and patient outcomes. This research could inform future trials and guidelines and improve practice. The ISPD-NARC is a network of PD units that has been formed to conduct multicenter studies in PD.

Citrate vs. acetate dialysate on intradialytic heparin dose: A double blind randomized crossover study.

Introduction Citrate containing dialysate has a calcium-binding anticoagulant effect compared to standard acetic acid containing dialysate. We performed a randomized, double-blind, crossover trial in maintenance HD patients to determine if citrate dialysate ("citrate") safely allows for a lower cumulative heparin dose ("heparin dose"). Methods Intradialytic heparin was adjusted to the minimum during a 2-week run-in phase. Patients remaining on heparin at the end of the run-in phase were then randomized to two weeks of HD with acetate dialysate ("acetate") followed by two weeks of citrate (sequence 1) or two weeks of citrate followed by two weeks of acetate (sequence 2). We estimated a minimum of 14 patients are required to show a 30% reduction in heparin dose per HD session with citrate compared with acetate. Twenty-five patients entered the run-in phase, 20 were randomized, and 19 completed the study. Findings The mean heparin dose was reduced by 19% (656 units, 95% CI -174 to -1139 units, P = 0.011) in the acetate group, and 30% (1046 units 95% CI -498 to 1594 units, P < 0.001) in the citrate group. There was no difference in the mean heparin dose reduction between the two dialysates (P > 0.05). The intradialytic ionized calcium in the citrate group was lowered by 0.10 mmol/L (95% CI 0.07 to 0.14 mmol/L, P < 0.001), and remained unchanged in the acetate group. Discussion Although citrate is a safe alternative to acetate, it does not result in additional heparin dose reduction.

Neighborhood socioeconomic status and barriers to peritoneal dialysis: a mixed methods study.

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the association between neighborhood socioeconomic status and barriers to peritoneal dialysis eligibility and choice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study was a mixed methods parallel design study using quantitative and qualitative data from a prospective clinical database of ESRD patients. The eligibility and choice cohorts were assembled from consecutive incident chronic dialysis patients entering one of five renal programs in the province of Ontario, Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was measured as median household income and percentage of residents with at least a high school education using Statistics Canada dissemination area-level data. Multivariable models described the relationship between socioeconomic status and likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal dialysis eligibility and choice were classified into qualitative categories using the thematic constant comparative approach. RESULTS: The peritoneal dialysis eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of patients were deemed eligible for peritoneal dialysis, and 46% of eligible patients chose peritoneal dialysis. Socioeconomic status was not a significant predictor of peritoneal dialysis eligibility or choice in this study. Qualitative analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower- versus higher-income Statistics Canada dissemination areas cited built environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and family or social support barriers (8.3% versus 3.5%) more frequently. CONCLUSIONS: Peritoneal dialysis eligibility and choice were not associated with socioeconomic status. However, socioeconomic status may influence specific barriers to peritoneal dialysis choice. Additional studies to determine the effect of targeting interventions to specific barriers to peritoneal dialysis choice in low socioeconomic status patients on peritoneal dialysis use are needed.