Key Points Is performing a large definitive trial to establish the optimal anticoagulation strategy in dialysis recipients with atrial fibrillation feasible?One hundred fifty-one patients at 28 dialysis centers were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48).Despite coronavirus disease–related pauses, recruitment was completed in 30 months, with 83% of participants completing follow-up in their assigned treatment arm. Background Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. Methods The Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centers in Canada and Australia. The trial included adults (18 years or older) undergoing dialysis with a history of nonvalvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: (1) recruitment of the target population within 2 years from the start of the trial and (2) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. Results From December 2019 to June 2022, 151 patients were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48). Allowing for pauses related to the coronavirus disease pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (four warfarin, two apixaban, two no oral anticoagulation). Death occurred in 15 participants (nine warfarin, two apixaban, four no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (interquartile range, 47%–70%). Conclusions We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis. Clinical Trial registry name and registration number: Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis (SAFE-D), NCT03987711.

Background Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. Methods The Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centers in Canada and Australia. The trial included adults (18 years or older) undergoing dialysis with a history of nonvalvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: (1) recruitment of the target population within 2 years from the start of the trial and (2) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. Results From December 2019 to June 2022, 151 patients were enrolled and randomized to apixaban (n=51), warfarin (n=52), or no oral anticoagulation (n=48). Allowing for pauses related to the coronavirus disease pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (four warfarin, two apixaban, two no oral anticoagulation). Death occurred in 15 participants (nine warfarin, two apixaban, four no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (interquartile range, 47%-70%). Conclusions We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.

In nephrology, point-of-care ultrasound (POCUS) has multiple applications including the rapid evaluation of acute kidney injury, enhancing the initial evaluation of chronic kidney disease, direct evaluation of vascular access, and improved fluid balance management in acute and chronic settings [1, 2]. Recently, the role of POCUS has been formally acknowledged by the American College of Physicians and curricula specific to nephrology have been proposed [3, 4]. However, the integration of a novel clinical skill into a field comes with its unique set of challenges. Above all, most nephrologists in leadership roles within fellowship training programs lack POCUS experience, which represent a significant barrier for adequate exposure and teaching. Although educational curriculum centered on nephrology have been proposed, the optimal model to ensure adequate POCUS exposure considering the scarcity of expertise among educators is not known.

BACKGROUND AND OBJECTIVES:Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. RESULTS:Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%. CONCLUSIONS:Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.

Rationale & Objective: Coronavirus disease 2019 (COVID-19) may be associated with high rates of acute kidney injury (AKI) and kidney replacement therapy (KRT), potentially overwhelming health care resources. Our objective was to determine the pooled prevalence of AKI and KRT among hospitalized patients with COVID-19. Study Design: Systematic review and metaanalysis. Data Sources: MEDLINE, Embase, the Cochrane Library, and a registry of preprinted studies, published up to October 14, 2020. Study Selection: Eligible studies reported the prevalence of AKI in hospitalized patients with COVID-19 according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Data Extraction & Synthesis: We extracted data on patient characteristics, the proportion of patients developing AKI and commencing KRT, important clinical outcomes (discharge from hospital, ongoing hospitalization, and death), and risk of bias. Outcomes & Measures: We calculated the pooled prevalence of AKI and receipt of KRT along with 95% CIs using a random-effects model. We performed subgroup analysis based on admission to an intensive care unit (ICU). Results: Of 2,711 records reviewed, we included 53 published and 1 preprint study in the analysis, which comprised 30,657 hospitalized patients with COVID-19. Data for AKI were available for 30,639 patients (n = 54 studies), and receipt of KRT, for 27,525 patients (n = 48 studies). The pooled prevalence of AKI was 28% (95% CI, 22%-34%; I-2 = 99%), and the pooled prevalence of KRT was 9% (95% CI, 7%-11%; I-2 = 97%). The pooled prevalence of AKI among patients admitted to the ICU was 46% (95% CI, 35%-57%; I-2 = 99%), and 19% of all ICU patients with COVID-19 (95% CI, 15%-22%; /I-2 = 88%) commenced KRT. Limitations: There was significant heterogeneity among the included studies, which remained unaccounted for in subgroup analysis. Conclusions: AKI complicated the course of nearly 1 in 3 patients hospitalized with COVID-19. The risk for AKI was higher in critically ill patients, with a substantial number receiving KRT at rates higher than the general ICU population. Because COVID-19 will be a public health threat for the foreseeable future, these estimates should help guide KRT resource planning.

Acute kidney injury (AKI) is a common complication of coronavirus disease 2019 (COVID-19) and is usually related to disease severity. Accordingly, it typically occurs in patients who are critically ill, those with pre-existing conditions, older adults and Black people.[1][1] Uncommon presentations

BACKGROUND:Quality metrics or indicators help guide quality improvement work by reporting on measurable aspects of health care upon which improvement efforts can focus. For recipients of in-center hemodialysis (ICHD) in Canada, it is unclear what ICHD quality indicators exist and whether they adequately cover different domains of health care quality.OBJECTIVES:To identify and evaluate current Canadian ICHD quality metrics to document a starting point for future collaborations and standardization of quality improvement in Canada.DESIGN:Environmental scan of quality metrics in ICHD, and subsequent indicator evaluation using a modified Delphi approach.SETTING:Canadian ICHD units.PARTICIPANTS:Sixteen-member pan-Canadian working group with expertise in ICHD and quality improvement.MEASUREMENTS:We classified the existing indicators based on the Institute of Medicine (IOM) and Donabedian frameworks.METHODS:Each metric was rated by a 5-person subcommittee using a modified Delphi approach based on the American College of Physicians/Agency for Healthcare Research and Quality criteria. We shared these consensus ratings with the entire 16-member panel for additional comments.RESULTS:We identified 27 metrics that are tracked across 8 provinces, with only 9 (33%) tracked by multiple provinces (ie, more than 1 province). We rated 9 metrics (33%) as "necessary" to distinguish high-quality from low-quality care, of which only 2 were tracked by multiple provinces (proportion of patients by primary access and rate of vascular access-related bloodstream infections). Most (16/27, 59%) indicators assessed the IOM domains of safe or effective care, and none of the "necessary" indicators measured the IOM domains of timely, patient-centered, or equitable care.LIMITATIONS:The environmental scan is a nonexhaustive list of quality indicators in Canada. The panel also lacked representation from patients, administrators, and allied health professionals, with more representation from academic sites.CONCLUSIONS:Quality indicators in Canada mainly focus on safe and effective care, with little provincial overlap. These results highlight current gaps in quality of care measurement for ICHD, and this initial work should provide programs with a starting point to combine highly rated indicators with newly developed indicators into a concise balanced scorecard that supports quality improvement initiatives across all aspects of ICHD care.TRIAL REGISTRATION:not applicable.

To optimize strategies that mitigate the risk of graft loss associated with HLA incompatibility, we evaluated whether sequence defined HLA targets (eplets) that result in donor-specific antibodies are associated with transplant outcomes. To define this, we fit multivariable Cox proportional hazard models in a cohort of 118 382 United States first kidney transplant recipients to assess risk of death-censored graft failure by increments of ten antibody-verified eplet mismatches. To verify robustness of our findings, we conducted sensitivity analysis in this United States cohort and assessed the role of antibody-verified eplet mismatches as autonomous predictors of transplant glomerulopathy in an independent Canadian cohort. Antibody-verified eplet mismatches were found to be independent predictors of death-censored graft failure with hazard ratios of 1.231 [95% confidence interval 1.195, 1. 268], 1.268 [1.231, 1.305] and 1.411 [1.331, 1.495] for Class I (HLA-A, B, and C), -DRB1 and -DQB1 loci, respectively. To address linkage disequilibrium between HLA-DRB1 and -DQB1, we fit models in a subcohort without HLA-DQB1 eplet mismatches and found hazard ratios for death-censored graft failure of 1.384 [1.293, 1.480] for each additional antibody-verified HLA-DRB1 eplet mismatch. In a subcohort without HLA-DRB1 mismatches, the hazard ratio was 1.384 [1.072, 1.791] for each additional HLA-DQB1 mismatch. In the Canadian cohort, antibody-verified eplet mismatches were independent predictors of transplant glomerulopathy with hazard ratios of 5.511 [1.442, 21.080] for HLA-DRB1 and 3.640 [1.574, 8.416] for -DRB1/3/4/5. Thus, donor-recipient matching for specific HLA eplets appears to be a feasible and clinically justifiable strategy to mitigate risk of graft loss.

Purpose: Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI. Methods: All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study. Results: The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%0:0.76-0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54-0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year. Conclusions: Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT. (C) 2019 Elsevier Inc. All rights reserved.

IntroductionStudies have shown that achieving a time in therapeutic range (TTR) for warfarin of greater than 60% is associated with a lower risk of bleeding. However, many patients on hemodialysis (HD) do not achieve this target.MethodsWe audited TTR achievement at the in-center HD unit of our hospital in 2017 and found that only 40% of patients had achieved a TTR >60%. We aimed to improve the percentage of HD patients achieving target TTR within 2 years. We reported each patient's individualized trend in quarterly TTR to their primary warfarin prescriber as an audit-feedback report. These reports were generated, disseminated, and subsequently improved following a series of plan-do-study-act cycles. We then used statistical process control to assess for changes in the percentage of HD patients achieving target TTR over time.ResultsIn the primary analysis, 28 patients were included in the baseline period, and 46 were included in the intervention period. At baseline, the percentage of patients achieving a TTR >60% varied between 33% and 45% (mean ± SD, 40% ± 5%); post-intervention, this metric improved and varied between 52% and 71% (mean ± SD, 61% ± 8%). In time-series analysis, there was evidence of statistically significant variation between the 2 periods and evidence of sustained improvement.ConclusionsA quality improvement program consisting of an audit-feedback report that raises awareness of the quality gap in TTR achievement can result in substantial improvement in the safe and efficacious administration of warfarin to patients receiving maintenance hemodialysis.

Introduction: Technological adjuncts have been developed to improve the accuracy of fluid removal goals in maintenance dialysis recipients. We aimed to determine whether the introduction of these tools has been shown to impact clinical outcomes. Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared fluid management guided by technological adjuncts to standard care in hemodialysis and peritoneal dialysis. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular events, hospitalizations, intradialytic hypotension, blood pressure, symptoms, antihypertensive medications. and left ventricular mass index. Results: Of the 2940 citations retrieved, we identified a total of 12 eligible trials comprising 2406 participants. In the 10 studies (n = 2111) with data on mortality, the use of adjunct technologies was not associated with a reduction of mortality (rate ratio [RR]: 0.92; confidence interval [CI]: 0.57-1.51; I-2 = 36%). The intervention conferred a reduction in systolic arterial pressure (mean difference: -3.14; CI: -5.89 to -0.38; I-2 = 39%) but did not affect other outcomes. In a subgroup analysis, bioimpedance was associated with a reduced risk of hospitalization (RR: 0.68; CI: 0.46-0.99; I-2 = 55%). The risk of bias was high or unclear in most studies and the quality of evidence was judged to be low. Conclusions: Among maintenance dialysis recipients, technological adjuncts for fluid management did not improve survival. Trials mostly investigated the use of bioimpedance, whereas the evidence for use of other technologies remain very scarce. Future adequately powered trials should assess a broader array of promising technologies using meaningful clinical outcomes over a prolonged follow-up duration.

RATIONALE & OBJECTIVE Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. STUDY DESIGN Retrospective population-based cohort study. SETTING & PARTICIPANTS All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. EXPOSURE Frequency of surveillance blood work, monthly versus every 6 weeks. OUTCOMES The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. ANALYTICAL APPROACH Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. RESULTS 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. LIMITATIONS Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. CONCLUSIONS Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.

PURPOSE OF REVIEW:Volume overload and hypovolemia-induced symptoms are common in the hemodialysis (HD) population and frequently result in emergency department visits and hospitalization. A structured strategy for the reporting, evaluation, and management of disordered volume status may improve clinical outcomes and the patient experience. We developed a new strategy that systematically addresses volume issues by leveraging the electronic medical record, technological adjuncts, and multidisciplinary expertise to institute new processes of care in our HD unit.SOURCES OF INFORMATION:This initiative was implemented in a unit located in an urban academic hospital where 250 patients receive maintenance HD. This initiative involved a multidisciplinary team of health professionals including physicians, nurse practitioners, social workers, and dieticians.METHODS:We generated volume metrics for HD recipients based on routinely collected data from the unit's electronic medical record. We then engaged stakeholders in a root cause analysis to identify the major causes of abnormal volume metrics locally. We subsequently developed interventions that were designed to address each of the major causes in a pragmatic and sustainable program.KEY FINDINGS:The final product was a local volume management program with 3 components. First, we integrated volume metric reporting into the routine surveillance bloodwork reports across our unit. This enabled the clinical teams to more easily target patients at risk for volume-related adverse events and provide them with closer surveillance. Those identified with abnormal volume metrics were then evaluated with the use of technologic adjuncts such as lung ultrasound and bioimpedance spectroscopy to complement traditional assessments of volume status. Finally, those with abnormal volume metrics underwent rigorous interdisciplinary review for potential nutritional/social interventions.LIMITATIONS:While we report the successful initial implementation of the program within a single center, it remains unclear whether this initiative will lead to meaningful benefits for HD recipients, be readily applicable in other centers, or be sustainable in the long term.IMPLICATIONS:This volume management program will need further evaluation linked to outcome assessment and feasibility in other centers before wider adoption is advocated.

Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady's TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus.