Search

Introduction: This study was designed to assess the association of age and frailty with clinical outcomes in patients with severe acute kidney injury (AKI), according to accelerated and standard renal-replacement therapy (RRT) initiation strategies in the STARRT-AKI trial. Methods: This was a secondary analysis of an international randomized trial. Older age was defined as ≥65 years. Frailty was assessed using the clinical frailty scale (CFS) score and defined as a score ≥5. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the impact of age and frailty on clinical outcomes. Results: Of 2,927 patients randomized in the STARRT-AKI trial, 1,616 (55.2%) were aged ≥65 years (median [interquartile range] 73.9 [69.4–78.9]). Older patients had greater comorbid cardiovascular and chronic kidney disease, were more likely to be surgical admissions and to receive vasopressors at baseline. Older patients had higher 90-day mortality (50.4% vs. 35.6%, adjusted-odds ratio (OR), 1.81 [1.53–2.13], p < 0.001). There was no significant difference in RRT dependence at 90 days between older and younger patients (8.7% vs. 7.8%, adjusted-OR, 1.21 [0.82–1.79], p = 0.325). Patients with frailty had higher mortality; but no difference in RRT dependence at 90 days. There was no significant interaction between age and CFS score in relation to mortality, RRT dependence at 90 days, and other secondary outcomes. There was no significant difference in the proportion of patients who received RRT in the standard-strategy stratified by age groups (adjusted-OR, 0.85 [0.67–1.08], p = 0.180). Conclusion: In this secondary analysis of the STARRT-AKI trial, older and frail patients had higher mortality at 90 days; however, there was no difference in RRT dependence. Mortality and RRT dependence were not modified by RRT initiation strategy in older or frail patients. Plain Language Summary: This study was designed to assess the association of age and frailty with clinical outcomes in patients with severe acute kidney failure using the data from an international randomized trial called the STARRT-AKI trial that examined the effect of timing of dialysis initiation on mortality in patients with acute kidney failure. In this study, older age was defined as ≥65 years, accounting for more than a half of the study population. This study demonstrated that older and frail patients carried higher mortality rates. However, age and frailty did not appear to have a significant impact on kidney recovery. Furthermore, in older or frail patients, timing of initiation of dialysis therapy did not affect mortality and kidney recovery. These findings will assist with triaging, prognostication, and management of older and frail patients with severe acute kidney failure in intensive care units. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT). Methods: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. Results: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was −288 mL (−904 to 261) with 20% HAS only versus 245 mL (−248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77–1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84–1.30; p = 0.70) compared to those who received 4% HAS only. Conclusions: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only. [ABSTRACT FROM AUTHOR]

Background: Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery. Methods: This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days. Results: Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66–0.91) and in those with >50% platelet decrease (HR 0.84, CI 0.72–0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90–0.97) and >50% platelet decrease (OR 0.91, CI 0.88–0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small. Conclusions: Platelet nadir <100 × 103/µL and platelet decrease by >50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT. [ABSTRACT FROM AUTHOR]

Introduction: Higher net ultrafiltration (UFNET) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT). Objective: The aim of the study was to discover whether UFNET rates are associated with renal recovery and independence from renal replacement therapy (RRT). Methods: Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UFNET rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UFNET rate was defined as the volume of fluid removed per hour adjusted for patient body weight. Results and Conclusions: Median age was 67.3 (interquartile range [IQR], 57–76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84–118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UFNET rates, 3 groups were defined: high, >1.75; middle, 1.01–1.75; and low, <1.01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0%; p = 0.01. Using competing risk regression, higher UFNET rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66–0.95; subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67–0.97) and lower (csHR, 0.69, 95% CI, 0.56–0.85; sHR, 0.78, 95% CI 0.64–0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74–0.89; and sHR, 0.87, 95% CI, 0.80–0.95). Using the joint model, longitudinal increases in UFNET rates were also associated with a lower renal recovery (β = −0.29, p < 0.001). UFNET rates >1.75 mL/kg/h compared with rates 1.01–1.75 and <1.01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UFNET rate-outcome relationship. [ABSTRACT FROM AUTHOR]

Introduction: In continuous renal replacement therapy (CRRT)-treated patients, a net ultrafiltration (NUF) rate >1.75 mL/kg/h has been associated with increased mortality. However, there may be heterogeneity of effect of NUF rate on mortality, according to patient characteristics. Methods: To investigate the presence and impact of heterogeneity of effect, we performed a secondary analysis of the "Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy" (RENAL) trial. Exposure was NUF rate (weight-adjusted fluid volume removed per hour) stratified into tertiles (<1.01 mL/kg/h; 1.01–1.75 mL/kg/h; or >1.75 mL/kg/h). Primary outcome was 90-day mortality. Patients were clustered according to baseline characteristics. Heterogeneity of effect was assessed according to clusters and baseline edema and related to the additional impact of baseline cardiovascular Sequential Organ Failure Assessment (SOFA) score. We excluded patients with missing values for baseline weight and/or treatment duration. Results: We identified 2 clusters. The largest (cluster 1; n = 941) included more severely ill patients, with more sepsis, more edema, and more vasopressor therapy (all p < 0.001). Compared to the middle tertile, the probability of harm was greater with the high tertile of NUF rate in patients in cluster 1 and in patients with baseline edema (probability of harm, cluster 1: 99.9%; edema: 99.1%). Moreover, higher baseline cardiovascular SOFA score also increased mortality risk with both high and low compared to middle NUF rates in cluster 1 patients and in patients with edema. Conclusions: In CRRT patients, both high and low NUF rates may be harmful, especially in those with edema, sepsis, and greater illness severity. Cardiovascular SOFA scores modulate this association. Additional studies are needed to test these hypotheses, and targeted trials of NUF rates based on risk stratification appear justified. Trial Registration: ClinicalTrials.gov identifier: NCT00221013. [ABSTRACT FROM AUTHOR]

Aims: To study the impact of early human albumin solution (HAS) in continuous renal replacement therapy (RRT) patients. Methods: Analysis of Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. Results: Of 1,464 patients, 500 (34%) received early albumin. These patients had higher illness severity scores, greater use of mechanical ventilation, and 90-day mortality (51 vs. 41%; p < 0.001). However, early albumin carried similar RRT dependence risk among survivors at day 90 (4.9 vs. 5.8%; p = 0.62). On Cox proportional hazards regression, with standardized inverse probability of treatment weighting, early albumin was not associated with increased mortality (hazard ratio [HR]: 1.23, 95% CI: 0.97–1.55; p = 0.09) or recovery to RRT independence (HR: 0.92, 95% CI: 0.78–1.10; p = 0.38). Conclusions: Early albumin was administered to one-third of RENAL trial patients and in those with greater illness severity. Early albumin was not independently associated with mortality risk or rate of recovery to RRT independence. [ABSTRACT FROM AUTHOR]

Aims: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. Methods: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). Conclusions: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Aims: The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. Methods: Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. Results: The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). Conclusions: Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to examine the association between dailyprotein intake (DPI) and outcomes in patients from the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Methods: We analyzed the association between DPI and clinical outcomes using multivariable logistic regression, Cox proportional hazards models and time-adjusted analysis. Results: During ICU stay, mean DPI was 37.6 g/day among survivors and 37.7 g/day among nonsurvivors (p = 0.96; DPI of 0.5 g/kg/day). Only 159 (10.9%) of the patients received a mean DPI of >1 g/kg. Patients with a DPI above the median had a 43.1% mortality compared with 46.1% for a DPI below the median (p = 0.25). On multivariate analysis, a lower DPI was not associated with increased odds ratios for 90-day mortality or any secondary outcomes. Cox proportional hazards models and time-adjusted analysis confirmed these findings. Conclusions: In the RENAL study, mean DPI was low. Within the confines of such low DPI, greater amounts of DPI were not independently associated with improved clinical outcomes. Video Journal Club 'Cappuccino with Claudio Ronco' at www.karger.com/?doi=363175. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objectives: Aspects of trial design, screening and study efficiency can affect recruitment and the findings of the trial itself. A clear understanding of the screening and study inclusion process will assist clinicians in interpreting trial results., Design: Prospective observational data collection on all patients screened for possible inclusion in a randomized controlled trial of normal vs. augmented renal replacement therapy in critically ill patients (the RENAL Trial)., Setting: 35 hospitals in Australia and New Zealand., Participants: All patients screened for the RENAL Trial., Results: We screened 4,551 patients. Of these patients, 767 were ineligible because of lack of inclusion criteria and 2,085 because of exclusion criteria. Of the remaining 1,699, 1,508 (88.7%) were enrolled. The three most common exclusion criteria which prevented recruitment of potentially eligible patients were that the patient had end-stage kidney failure and was already on chronic dialysis (484; 23.2%), the patient's body weight was either <60 or >120 kg (456; 21.8%), and the fact that the patient had already received renal replacement therapy during the index admission. Important modifiable impediments to recruitment were inability to obtain consent in 191 cases, unavailability of research staff in 124 cases, physician objection in 89 cases, and inability to deliver the trial protocol in 78 cases., Conclusion: The RENAL Trial's enrolment efficiency was high and compared favourably with previous large intensive care units trials and with that of trials in patients with acute renal failure. The high rate of enrolment suggests that the results can be applied with confidence to most patients with de novo acute renal failure. The loss of close to 1.5% of patients due to consent issues highlights a common problem in critical care trials. The low rate of physician objection suggests clinical equipoise.

Background/aims: The optimal dose of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain., Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Trial tests the hypothesis that higher dose continuous veno-venous hemodiafiltration (CVVHDF) at an effluent rate of 40 ml/kg/h will increase survival compared to CVVHDF at 25 ml/kg/h of effluent dose., Results: This trial is currently randomizing critically ill patients in 35 intensive care units in Australia and New Zealand with a planned sample size of 1,500 patients. This trial will be the largest trial ever conducted on acute blood purification in critically ill patients., Conclusion: A trial of this magnitude and with demanding technical requirements poses design difficulties and challenges in the logistics, conduct, data collection, data analysis and monitoring. Our report will assist in the development of future trials of blood purification in intensive care.