The risk of hospitalization and modality failure with home dialysis

While home dialysis is being promoted, there are few comparative effectiveness studies of home-based modalities to guide patient decisions. To address this, we matched 1116 daily home hemodialysis (DHD) patients by propensity scores to 2784 contemporaneous USRDS patients receiving home peritoneal dialysis (PD), and compared hospitalization rates from cardiovascular, infectious, access-related or bleeding causes (prespecified composite), and modality failure risk. We performed similar analyses for 1187 DHD patients matched to 3173 USRDS patients receiving in-center conventional hemodialysis (CHD). The composite hospitalization rate was significantly lower with DHD than with PD (0.93 vs. 1.35/patient-year, hazard ratio=0.73 (95% CI=0.67–0.79)). DHD patients spent significantly fewer days in hospital than PD patients (5.2 vs. 9.2 days/patient-year), and significantly more DHD patients remained admission-free (52% DHD vs. 32% PD). In contrast, there was no significant difference in hospitalizations between DHD and CHD (DHD vs. CHD: 0.93 vs. 1.10/patient-year, hazard ratio 0.92 (0.85–1.00)). Cardiovascular hospitalizations were lower with DHD than with CHD (0.68 (0.61–0.77)), while infectious and access hospitalizations were higher (1.15 (1.04–1.29) and 1.25 (1.08–1.43), respectively). Significantly more PD than DHD patients switched back to in-center HD (44% vs. 15%; 3.4 (2.9–4.0)). In this prevalent cohort, home DHD was associated with fewer admissions and hospital days than PD, and a substantially lower risk of modality failure

Minimally important difference estimates and methods: A protocol

Introduction: Patient-reported outcomes (PROs) are often the outcomes of greatest importance to patients. The minimally important difference (MID) provides a measure of the smallest change in the PRO that patients perceive as important. An anchor-based approach is the most appropriate method for MID determination. No study or database currently exists that provides all anchor-based MIDs associated with PRO instruments; nor are there any accepted standards for appraising the credibility of MID estimates. Our objectives are to complete a systematic survey of the literature to collect and characterise published anchor-based MIDs associated with PRO instruments used in evaluating the effects of interventions on chronic medical and psychiatric conditions and to assess their credibility. Methods and analysis: We will search MEDLINE, EMBASE and PsycINFO (1989 to present) to identify studies addressing methods to estimate anchor-based MIDs of target PRO instruments or reporting empirical ascertainment of anchor-based MIDs. Teams of two reviewers will screen titles and abstracts, review full texts of citations, and extract relevant data. On the basis of findings from studies addressing methods to estimate anchor-based MIDs, we will summarise the available methods and develop an instrument addressing the credibility of empirically ascertained MIDs. We will evaluate the credibility of all studies reporting on the empirical ascertainment of anchorbased MIDs using the credibility instrument, and assess the instrument's inter-rater reliability. We will separately present reports for adult and paediatric populations. Ethics and dissemination: No research ethics approval was required as we will be using aggregate data from published studies. Our work will summarise anchor-based methods available to establish MIDs, provide an instrument to assess the credibility of available MIDs, determine the reliability of that instrument, and provide a comprehensive compendium of published anchor-based MIDs associated with PRO instruments which will help improve the interpretability of outcome effects in systematic reviews and practice guidelines

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Benefits and harms of citrate locking solutions for hemodialysis catheters: a systematic review and meta-analysis

Abstract Background Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. Objectives 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence. Data sources CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. Study eligibility, participants, and interventions We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics. Appraisal and synthesis methods We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate. Results We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42-1.24; p = 0.21; I2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23-1.29; p = 0.16; I2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3-0.75; p = 0.001;I I2 = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low. Limitations Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. Implications Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. Trial registration Protocol Registration Number: CRD4201300478

Comparative Effectiveness of Home Dialysis Therapies: A Matched Cohort Study

Background: Home dialysis is being increasingly promoted among patients with end-stage renal disease, but the comparative effectiveness of home hemodialysis and peritoneal dialysis is unknown. Objective: To determine whether patients receiving home daily hemodialysis have reduced mortality risk compared with matched patients receiving home peritoneal dialysis. Design: This study is an observational, propensity-matched, new-user cohort study. Setting: Linked electronic data were from the United States Renal Data System (USRDS) and a large dialysis provider's database. Patients: The patients were adults receiving in-center hemodialysis in the USA between 2004 and 2011 and registered in the USRDS. Measurements: Baseline comorbidities, demographics, and outcomes for both groups were ascertained from the United States Renal Data System. Methods: We identified 3142 consecutive adult patients initiating home daily hemodialysis (≥5 days/week for ≥1.5 h/day) and matched 2688 of them by propensity score to 2688 contemporaneous US patients initiating home peritoneal dialysis. We used Cox regression to compare all-cause mortality between groups. Results: After matching, the two groups were well balanced on all baseline characteristics. Mean age was 51 years, 66 % were male, 72 % were white, and 29 % had diabetes. During 10,221 patient-years of follow-up, 1493/5336 patients died. There were significantly fewer deaths among patients receiving home daily hemodialysis than those receiving peritoneal dialysis (12.7 vs 16.7 deaths per 100 patient-years, respectively; hazard ratio (HR) 0.75; 95 % CI 0.68–0.82; p < 0.001). Similar results were noted with several different analytic methods and for all pre-specified subgroups. Limitations: We cannot exclude residual confounding in this observational study. Conclusions: Home daily hemodialysis was associated with lower mortality risk than home peritoneal dialysis

Benefits and Harms of Citrate Locking Solutions for Hemodialysis Catheters: A Systematic Review and Meta-Analysis

Background: Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. Objectives: 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence. Data sources: CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. Study eligibility, participants, and interventions: We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics. Appraisal and synthesis methods: We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate. Results: We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42–1.24; p = 0.21; I 2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23–1.29; p = 0.16; I 2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3–0.75; p = 0.001;I I 2 = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low. Limitations: Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. Implications: Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. Trial registration: Protocol Registration Number: CRD4201300478

Attitudes and Opinions of Canadian Nephrologists Toward Continuous Quality Improvement Options

Background and objectives: A shift to holding individual physicians accountable for patient outcomes, rather than facilities, is intuitively attractive to policy makers and to the public. We were interested in nephrologists’ attitudes to, and awareness of, quality metrics and how nephrologists would view a potential switch from the current model of facility-based quality measurement and reporting to publically available reports at the individual physician level. Design, setting, participants, and measurements: The study was conducted using a web-based survey instrument (Online Appendix 1). The survey was initially pilot tested on a group of 8 nephrologists from across Canada. The survey was then finalized and e-mailed to 330 nephrologists through the Canadian Society of Nephrology (CSN) e-mail distribution list. The 127 respondents were 80% university based, and 33% were medical/dialysis directors. Results: The response rate was 43%. Results demonstrate that 89% of Canadian nephrologists are engaged in efforts to improve the quality of patient care. A minority of those surveyed (29%) had training in quality improvement. They feel accountable for this and would welcome the inclusion of patient-centered metrics of care quality. Support for public reporting as an effective strategy on an individual nephrologist level was 30%. Conclusions: Support for public reporting of individual nephrologist performance was low. The care of nephrology patients will be best served by the continued development of a critical mass of physicians trained in patient safety and quality improvement, by focusing on patient-centered metrics of care delivery, and by validating that all proposed new methods are shown to improve patient care and outcomes

Mortality and Hospitalizations in Intensive Dialysis: A Systematic Review and Meta-Analysis

Background: Survival and hospitalization are critically important outcomes considered when choosing between intensive hemodialysis (HD), conventional HD, and peritoneal dialysis (PD). However, the comparative effectiveness of these modalities is unclear. Objective: We had the following aims: (1) to compare the association of mortality and hospitalization in patients undergoing intensive HD, compared with conventional HD or PD and (2) to appraise the methodological quality of the supporting evidence. Data Sources: MEDLINE, Embase, ISI Web of Science, CENTRAL, and nephrology conference abstracts. Study Eligibility, Participants, and Interventions: We included cohort studies with comparator arm, and randomized controlled trials (RCTs) with >50% of adult patients (≥18 years) comparing any form of intensive HD (>4 sessions/wk or >5.5 h/session) with any form of chronic dialysis (PD, HD ≤4 sessions/wk or ≤5.5 h/session), that reported at least 1 predefined outcome (mortality or hospitalization). Methods: We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers screened citations and full-text articles, and extracted study-level data independently, with discrepancies resolved by consensus. We pooled effect estimates of randomized and observational studies separately using generic inverse variance with random effects models, and used fixed-effects models when only 2 studies were available for pooling. Predefined subgroups for the intensive HD cohorts were classified by nocturnal versus short daily HD and home versus in-center HD. Results: Twenty-three studies with a total of 70 506 patients were included. Of the observational studies, compared with PD, intensive HD had a significantly lower mortality risk (hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.53-0.84; I 2 = 91%). Compared with conventional HD, home nocturnal (HR: 0.46; 95% CI: 0.38-0.55; I 2 = 0%), in-center nocturnal (HR: 0.73; 95% CI: 0.60-0.90; I 2 = 57%) and home short daily (HR: 0.54; 95% CI: 0.31-0.95; I 2 = 82%) intensive regimens had lower mortality. Of the 2 RCTs assessing mortality, in-center short daily HD had lower mortality (HR: 0.54; 95% CI: 0.31-0.93), while home nocturnal HD had higher mortality (HR: 3.88; 95% CI: 1.27-11.79) in long-term observational follow-up. Hospitalization days per patient-year (mean difference: –1.98; 95% CI: –2.37 to −1.59; I 2 = 6%) were lower in nocturnal compared with conventional HD. Quality of evidence was similarly low or very low in RCTs (due to imprecision) and observational studies (due to residual confounding and selection bias). Limitations: The overall quality of evidence was low or very low for critical outcomes. Outcomes such as quality of life, transplantation, and vascular access outcomes were not included in our review. Conclusions: Intensive HD regimens may be associated with reduced mortality and hospitalization compared with conventional HD or PD. As the quality of supporting evidence is low, patients who place a high value on survival must be adequately advised and counseled of risks and benefits when choosing intensive dialysis. Practice guidelines that promote shared decision-making are likely to be helpful

Quality of Care for Patients With Chronic Kidney Disease in the Primary Care Setting: A Retrospective Cohort Study From Ontario, Canada

Background: Patients with chronic kidney disease may not be receiving recommended primary renal care. Objective: To use recently established primary care quality indicators for chronic kidney disease to determine the proportion of patients receiving recommended renal care. Design: Retrospective cohort study using administrative data with linked laboratory information. Setting: The study was conducted in Ontario, Canada, from 2006 to 2012. Patients: Patients over 40 years with chronic kidney disease or abnormal kidney function in primary care were included. Measurements: In total, 11 quality indicators were assessed for chronic kidney disease identified through a Delphi panel in areas of screening, monitoring, drug prescribing, and laboratory monitoring after initiating an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Methods: We calculated the proportion and cumulative incidence at the end of follow-up of patients meeting each indicator and stratified results by age, sex, cohort entry, and chronic kidney disease stage. Results: Less than half of patients received follow-up tests after an initial abnormal kidney function result. Most patients with chronic kidney disease received regular monitoring of serum creatinine (91%), but urine albumin-to-creatinine monitoring was lower (70%). A total of 84% of patients age 66 and older did not receive a non-steroidal anti-inflammatory drug prescription of at least 2-week duration. Three quarters of patients age 66 and older were on an ACE inhibitor or ARB, and 96% did not receive an ACE inhibitor and ARB concurrently. Among patients 66 to 80 years of age with chronic kidney disease, 65% were on a statin. One quarter of patients age 66 and older who initiated an ACE inhibitor or ARB had their serum creatinine and potassium monitored within 7 to 30 days. Limitations: This study was limited to people in Ontario with linked laboratory information. Conclusions: There was generally strong performance across many of the quality of care indicators. Areas where more attention may be needed are laboratory testing to confirm initial abnormal kidney function test results and monitoring serum creatinine and potassium after initiating a new ACE inhibitor or ARB