Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain.
We ...conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days.
Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval CI, 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001).
Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing ...consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.
Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain.
To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in ...adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD).
English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019).
Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes.
Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence.
Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio RR, 0.79 95% CI, 0.66 to 0.93; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 CI, 0.30 to 0.76; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 CI, 0.44 to 1.17; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 CI, 0.56 to 1.01; low-certainty evidence).
Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials.
In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs.
None. (PROSPERO: CRD42017079709).
The relative merits of buttonhole (or blunt needle) versus rope ladder (or sharp needle) cannulation for hemodialysis vascular access are unclear.
Clinical outcomes by cannulation method were ...reviewed in 90 consecutive home hemodialysis patients. Initially, patients were trained in rope ladder cannulation. From 2004 on, all incident patients were started on buttonhole cannulation, and prevalent patients were converted to this cannulation method. Coprimary outcomes were arteriovenous fistula-attributable systemic infections and a composite of arteriovenous fistula loss or requirement for surgical intervention. Secondary outcomes were total arteriovenous fistula-related infections and staff time requirements. Additionally, a systematic review evaluating infections by cannulation method was performed.
Seventeen systemic arteriovenous fistula-attributable infections were documented in 90 patients who were followed for 3765 arteriovenous fistula-months. Compared with rope ladder, buttonhole was not associated with a significantly higher rate of systemic arteriovenous fistula-attributable infections (incidence rate ratio, 2.71; 95% confidence interval, 0.66 to 11.09; P=0.17). However, use of buttonhole was associated with a significantly higher rate of total arteriovenous fistula infections (incidence rate ratio, 3.85; 95% confidence interval, 1.66 to 12.77; P=0.03). Initial and ongoing staff time requirements were significantly higher with buttonhole cannulation. Arteriovenous fistula loss or requirement for surgical intervention was not different between cannulation methods. A systematic review found increased arteriovenous fistula-related infections with buttonhole compared with rope ladder in four randomized trials (relative risk, 3.34; 95% confidence interval, 0.91 to 12.20), seven observational studies comparing before with after changes (relative risk, 3.15; 95% confidence interval, 1.90 to 5.21), and three observational studies comparing units with different cannulation methods (relative risk, 3.27; 95% confidence interval, 1.44 to 7.43).
Buttonhole cannulation was associated with higher rates of infectious events, increased staff support requirements, and no reduction in surgical arteriovenous fistula interventions compared with rope ladder in home hemodialysis patients. A systematic review of the published literature found that buttonhole is associated with higher risk of arteriovenous fistula-related infections.
Abstract
Background
Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes ...among individuals with greater fluid overload at randomization.
Methods
We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables.
Results
Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (− 728 to 11,698) versus 5646 (0 to 13,151) mL,
p
= 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03),
p
value for trend 0.08).
Conclusions
Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality.
Trial registration
: ClinicalTrials.gov number,
https://clinicaltrials.gov/ct2/show/NCT02568722
, registered October 6, 2015.
Clinical trials are most informative for evidence-based decision making when they consistently measure and report outcomes of relevance to stakeholders. We aimed to assess the scope and consistency ...of outcomes reported in trials for hemodialysis.
Systematic review.
Adults requiring maintenance hemodialysis enrolled in clinical trials.
All Cochrane systematic reviews of interventions published by August 29, 2016, and the trials published and registered in ClinicalTrials.gov since January 2011.
Any hemodialysis-related interventions.
Frequency and characteristics of the reported outcome domains and measures.
From the 362 trials, we extracted and classified 10,713 outcome measures (a median of 21 IQR, 10-39 per trial) into 81 different outcome domains, of which 42 (52%) were surrogate; 25 (31%), clinical; and 14 (17%), patient reported. The number of outcome measures reported significantly changed over time. The 5 most commonly reported domains were all surrogates: phosphate (125 35% trials), dialysis adequacy (120 33%), anemia (115 32%), inflammatory markers (114 31%), and calcium (109 30%). Mortality, cardiovascular diseases, and quality of life were reported very infrequently (73 20%, 44 12%, and 32 9%, respectively).
For feasibility, we included a sampling frame that included only trials identified in Cochrane systematic reviews or ClinicalTrials.gov.
Outcomes reported in clinical trials involving adults receiving hemodialysis are focused on surrogate outcomes, rather than clinical and patient-centered outcomes. There is also extreme multiplicity and heterogeneity at every level: domain, measure, metric, and time point. Estimates of the comparative effectiveness of available interventions are unreliable and improvements over time have been inconsistent.
Background Whether convective modalities of dialysis, including hemofiltration (HF) and hemodiafiltration (HDF), improve cardiovascular outcomes and mortality is unclear. Study Design Systematic ...review and meta-analysis. Setting & Population Patients receiving HDF, HF, or standard hemodialysis (HD). Selection Criteria for Studies Randomized controlled trials. Intervention Convective modalities of dialysis (HDF and HF) versus standard HD. Outcomes The primary outcome was clinical cardiovascular outcomes. Secondary outcomes were all-cause mortality, episodes of symptomatic hypotension, dialysis adequacy, and β2 -microglobulin level. Relative risks (RRs) or weighted mean differences with 95% CIs for individual trials were pooled using random-effects models. Results The search yielded 16 trials including 3,220 patients. Therapies assessed were convective modalities (HDF or HF) compared with standard HD. Compared with HD, convective modalities did not significantly reduce the risk of cardiovascular events (RR, 0.85; 95% CI, 0.66-1.10) or all-cause mortality (RR, 0.83; 95% CI, 0.65-1.05). Convective modalities reduced symptomatic hypotension (RR, 0.49; 95% CI, 0.30-0.81) and improved serum β2 -microglobulin levels (−5.95 mg/L; 95% CI, −10.27 to −1.64), but had no impact on small-molecule clearance (weighted mean difference in Kt/V, 0.04; 95% CI, −0.04 to 0.12). There was a nonsignificant trend to a greater likelihood of receiving a kidney transplant for participants allocated to filtration therapies (RR, 1.19; 95% CI, 0.99-1.42). Limitations The trials were predominantly of suboptimal quality and underpowered, with imbalance in some prognostic variables at baseline. Intention-to-treat analysis was not used in some trials. Our analysis was limited to published outcomes. Conclusions The potential benefits of convective modalities over standard HD for cardiovascular outcomes and mortality remain unproved. Further high-quality randomized trials are needed to define the impact of these modalities on clinically important outcomes.
The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based ...hemodialysis programs to extended weekly (≥24 hours) or standard (target 12-15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6-24.0) and 12.0 (interquartile range, 12.0-16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 95% confidence interval, -0.03 to 0.11;
=0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, -6.0 95% confidence interval, -14.8 to 2.7 g/m
;
=0.18). Five deaths occurred in the extended group and two in the standard group (
=0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298).
The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease (CKD) population.
Cardiovascular and possibly bleeding risks are ...elevated in patients with CKD. The balance of benefit and harm associated with antiplatelet therapy remains uncertain.
The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR) with trends tested by adding interaction terms. End points included major cardiovascular events, total mortality, and major bleeding.
The study included 18,597 participants treated for 3.8 years. Baseline eGFR was < 60 ml/min/1.73 m(2) in 3,619 participants. Major cardiovascular events were reduced by 9% (95% confidence interval CI: -9% to 24%), 15% (95% CI: -17% to 39%), and 66% (95% CI: 33% to 83%) for patients with baseline eGFR of ≥ 60, 45 to 59, and < 45 ml/min/1.73 m(2), respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI: -20% to 17%), 11% (95% CI: -31% to 40%), and 49% (95% CI: 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR (hazard ratio HR: 1.52 95% CI: 1.11 to 2.08, HR: 1.70 95% CI: 0.74 to 3.88, and HR: 2.81 95% CI: 0.92 to 8.84, respectively; p trend = 0.30). Among every 1,000 persons with eGFR < 45 ml/min/1.73 m(2) treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur.
Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.
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