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Background. The obective of this study was to perform a costeffectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). Methods. Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from $200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). Results. Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental costeffectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. Conclusions. Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivors. [ABSTRACT FROM AUTHOR]

Recovery of kidney function following an episode of acute kidney injury (AKI) is now acknowledged as a vital patient-centered outcome with clear health economic implications. In approximately 5-8% of critically ill patients with more severe forms of AKI, support with renal replacement therapy (RRT) is provided. Recent data have suggested that rates of RRT utilization in AKI are increasing. Despite advances in our understanding of how best to prescribe acute RRT in critically ill patients with AKI, additional aspects remain uncertain, predisposing to suboptimal delivery and variation in practice. Importantly, if, when, how, and by what principles we apply acute RRT for AKI are all treatment decision-related factors that are modifiable and may interact with recovery of kidney function. Limited data, mostly from observational studies and secondary analyses, have explored the specific association between acute RRT and recovery. Available data are not able to clarify whether providing any RRT in otherwise eligible patients with AKI impacts recovery. They are also unable to inform whether the timing or circumstance under which RRT is started impacts recovery. No studies have evaluated whether there is an optimal time to start RRT to maximize the probability of recovery. Accumulated evidence, mostly derived from observational studies, suggests initial therapy in critically ill patients with AKI with continuous RRT, compared with intermittent modalities, improves the probability of recovery to dialysis independence. Evidence from high-quality randomized trials failed to show any association between delivered dose intensity of RRT and recovery. The use of biocompatible membranes for acute RRT may improve recovery in AKI; however, data are inconsistent. Limited data have evaluated the impact of membrane flux properties on recovery. Preliminary data have suggested that circuit anticoagulation with citrate, which results in a reduction in membrane-induced oxidative stress and leukocyte activation, may be associated with improved recovery; however, further corroborative data are needed. Additional evidence, ideally from randomized trials, is clearly needed to inform best practice in the delivery of acute RRT to optimize probability of recovery of kidney function for survivors of AKI. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients. Methods: We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL and uNGAL] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L. Measurements and main results: Bland-Altman analysis demonstrated that, despite correlating well ( r = 0.988), uNGAL and uNGAL were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03-450.44 ng/mg creatinine; limits of agreement: −1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction. Conclusions: uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker. [ABSTRACT FROM AUTHOR]

Purpose: Choice of renal replacement therapy (RRT) modality may affect renal recovery after acute kidney injury (AKI). We sought to compare the rate of dialysis dependence among severe AKI survivors according to the choice of initial renal replacement therapy (RRT) modality applied [continuous (CRRT) or intermittent (IRRT)]. Methods: Systematic searches of peer-reviewed publications in MEDLINE and EMBASE were performed (last update July 2012). All studies published after 2000 reporting dialysis dependence among survivors from severe AKI requiring RRT were included. Data on follow-up duration, sex, age, chronic kidney disease, illness severity score, vasopressors, and mechanical ventilation were extracted when available. Results were pooled using a random-effects model. Results: We identified 23 studies: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % confidence interval (CI) 0.78-1.68], I = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IRRT as compared with CRRT (RR 1.99 [95 % CI 1.53-2.59], I = 42 %). These findings were consistent with adjusted analyses (performed in 7/16 studies), which found a higher rate of dialysis dependence in IRRT-treated patients [odds ratio (OR) 2.2-25 (5 studies)] or no difference (2 studies). Conclusions: Among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT. However, this finding largely relies on data from observational trials, potentially subject to allocation bias, hence further high-quality studies are necessary. [ABSTRACT FROM AUTHOR]

Background. Only a proportion of critically ill patients with severe [RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria, class-F] acute kidney injury (AKI) appear to receive renal replacement therapy (RRT). The aim of this study was to study the characteristics and outcome of patients with severe (RIFLE-F) AKI who did not receive RRT. Methods. We identified all consecutive patients admitted to our institution that developed RIFLE-F AKI by creatinine criteria over a 3-year period and did not receive RRT, and compared their characteristics and outcomes with those of RIFLE-F RRT-treated patients. Results. Within the study period, 20 126 patients were admitted to our institution for >24 h. Among them, 2949 were admitted to the intensive care unit (ICU) and 195 developed RIFLE-F AKI. Of these, 90 received RRT (RRT patients) and 105 did not (no-RRT patients). Compared with RRT patients, no-RRT patients were similar in terms of age, gender and ward of origin. However, they had a shorter median ICU stay (2.7 versus 7.9 days; P < 0.001), required less mechanical ventilation (56.2 versus 70%; P < 0.05) and had a lower mean Acute Physiology and Chronic Health Evaluation III score (82.7 versus 86.7; P < 0.05). The two main reasons these patients did not receive RRT were limitations of medical therapy (LOMT) orders in 41 (39%) cases and expected renal functional improvement in 59 (56.2%). Mortality in no-RRT patients was 58.1% compared with 55.5% in the RRT group (P = 0.72). After exclusion of LOMT patients, the mortality of the no-RRT group, although lower than that of the RRT group, remained high (30.5 versus 55%; P < 0.001). Most of these deaths occurred after ICU discharge and appeared secondary to underlying chronic diseases or recurrence of the initial insult. Conclusions. After exclusion of LOMT patients, about a third of critically ill patients with severe (RIFLE-F) AKI did not receive RRT. A third of these patients died in hospital. The timing of the deaths and their underlying causes do not suggest that a broader application of RRT would have changed patient outcomes. [ABSTRACT FROM PUBLISHER]

Background: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). Methods: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. Results: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75–1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66–0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39–0.94). Conclusions: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days. [ABSTRACT FROM AUTHOR]

Objectives: Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge.Design: Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database.Setting: Two hundred ninety-one ICUs in France.Patients: A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis.Interventions: None.Measurements Main Results: PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958.Conclusions: In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited. [ABSTRACT FROM AUTHOR]

Patients under extra-corporeal membrane oxygenation (ECMO) are at high risk of developing acute kidney injury and renal replacement therapy (RRT) is frequently needed. The aim of this study was to explore RRT use in ECMO patients, as no recommendations exist in this setting. An online questionnaire about RRT management in ECMO patients was sent to the members of the ARCOTHOVA (Anesthésie-Réanimation Coeur-Thorax-Vaisseaux) association and to the GFRUP (Groupe Francophone de Réanimation et Urgences Pédiatriques). Ninety intensivists from adult ICU and twenty from paediatric ICU responded to the questionnaire. RRT use was common as 67% respondents reported that more than 25% of their ECMO patients needed RRT. RRT indications were similar between centres, with persistent anuria (83%), metabolic acidosis (80%), fluid overload (78%) and hyperkalaemia (80%) being the more prevalent. Continuous renal replacement therapy was the preferred technique (97%). Continuous veno-venous haemofiltration was predominant (64%) over continuous veno-venous haemodiafiltration (21%). Unfractionated heparin was employed as first line choice anticoagulation in 61% and regional citrate anticoagulation in 16%. Integration of RRT device directly into the ECMO circuit was the preferred configuration (40%) while parallel systems with separate catheter were used in 30%. When the integrated approach was chosen, RRT device was most frequently connected with inlet and outlet lines after the ECMO pump (58%) and pressure alarms were encountered for 60% of participants. Our results highlight the high variability of practice between centres. They suggest the need to compare the integrated and parallel configurations of combining RRT and ECMO. [ABSTRACT FROM AUTHOR]

It was recently proposed to distinguish early from late sepsis-associated acute kidney injury (SA-AKI). We aimed to determine the relative frequency of these entities in critically ill patients and to describe their characteristics and outcomes. We included in this retrospective cohort study all adult patients admitted for sepsis in a tertiary ICU between 2010 and 2020. We excluded those on chronic dialysis or without consent. We extracted serum creatinine, hourly urinary output, and clinical and socio-demographic data from medical records until day 7 or ICU discharge. AKI presence and characteristics were assessed daily using KDIGO criteria. We compared patients with early (occurring within 2 days of admission) or late (occurring between day 2 and day 7) SA-AKI. We conducted sensitivity analyses using different definitions for early/late SA-AKI. Among 1835 patients, 1660 (90%) fulfilled SA-AKI criteria. Of those, 1610 (97%) had early SA-AKI, and 50 (3%) had late SA-AKI. Similar proportions were observed when only considering AKI with elevated sCr (71% vs. 3%), severe AKI (67% vs. 6%), or different time windows for early SA-AKI. Compared with early SA-AKI patients, those with late SA-AKI were younger (median age [IQR] 59 [49–70] vs. 69 [58–76] years, p < 0.001), had lower Charlson comorbidity index (3 [1–5] vs. 5 [3–7], p < 0.001) and lower SAPSII scores (41 [34–50] vs. 53 [43–64], p < 0.001). They had similar (24% vs. 26%, p = 0.75) in-hospital mortality. AKI is almost ubiquitous in septic critically ill patients and present within two days of admission. The timing from ICU admission might not be relevant to distinguish different phenotypes of SA-AKI. Ethics Committee Vaud, Lausanne, Switzerland (n°2017-00008). [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is now recognized as a heterogeneous syndrome that not only affects acute morbidity and mortality, but also a patient's long-term prognosis. In this narrative review, an update on various aspects of AKI in critically ill patients will be provided. Focus will be on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI), aspects of pathophysiology and progress in the recognition of different phenotypes of AKI, as well as an update on nephrotoxicity and organ cross-talk. In addition, prevention of AKI (focusing on fluid management, kidney perfusion pressure, and the choice of vasopressor) and supportive treatment of AKI is discussed. Finally, post-AKI risk of long-term sequelae including incident or progression of chronic kidney disease, cardiovascular events and mortality, will be addressed. [ABSTRACT FROM AUTHOR]

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified. [ABSTRACT FROM AUTHOR]

Background: Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setting of established AKI. Here, we present the protocol and statistical analysis plan of the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-the REVERSE-AKI trial that compares a restrictive fluid therapy regimen to standard therapy in critically ill patients with AKI.Methods: REVERSE-AKI is an investigator-initiated, multinational, open-label, randomized, controlled, feasibility pilot trial conducted in seven ICUs in five countries. We aim to randomize 100 critically ill patients with AKI to a restrictive fluid treatment regimen vs standard management. In the restrictive fluid therapy regimen, the daily fluid balance target is neutral or negative. The primary outcome is the cumulative fluid balance assessed after 72 hours from randomization. Secondary outcomes include safety, feasibility, duration, and severity of AKI, and outcome at 90 days (mortality and dialysis dependence).Conclusions: This is the first multinational trial investigating the feasibility and safety of a restrictive fluid therapy regimen in critically ill patients with AKI.Trial Registration: clinical.trials.gov NCT03251131. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common in critically ill patients and associated with grim short- and long-term outcome. Although in the vast majority of cases AKI is multifactorial, with sepsis, shock and nephrotoxicity accounting for most episodes, specific causes of AKI are not uncommon. Despite remaining uncertainties regarding their prevalence in the ICU, prompt recognition of specific aetiologies of AKI is likely to ensure timely management, limit worsening of renal dysfunction, and ultimately limit renal and systemic consequences of AKI. The ability to recognize conditions that may be associated with specific aetiologies and the appropriate use of clinical imaging, biological and immunological tests, along with optimal assessment of the need for renal biopsies, should be part of routine ICU care. In this review, we summarize uncertainties, current knowledge and recent advances regarding specific types of AKI. We describe the most common specific causes as well as rare aetiologies requiring urgent management, and outline available tools that may be used during the diagnostic work-up along with their limitations. [ABSTRACT FROM AUTHOR]

Background: Omni ® (B. Braun, Germany) is a new-generation, continuous renal replacement therapy (CRRT) machine designed to improve user interface, minimize downtime and optimize renal dose delivery. It was never tested in humans. Methods: We used Omni ® to provide CRRT in 10 critically ill patients. We collected therapy data, metabolic parameters and evaluated user's satisfaction with a survey. Results: CRRT was delivered using Omni ® in CVVH-heparin (6 patients) and CVVHD-citrate (4 patients) modes for a total duration of 617.7 h. No adverse event was observed. The mean filter life was 22.8 (CVVH-heparin) and 33.5 (CVVHD-citrate) h. Alarms-related downtime corresponded to 5.9% of total therapy time. Delivered renal dose was 96.6% of prescribed. Satisfactory metabolic control and fluid removal were achieved. Overall, users evaluated interface, design and usability as excellent. Conclusion: CRRT in CVVH-heparin and CVVHD-citrate modes was provided using Omni ® in a safe and efficient way for 10 critically ill patients. [ABSTRACT FROM AUTHOR]

Objective: To test the precision and limits of agreement of point-of-care testing (POCT)-based measurement of serum creatinine (Cr) in critically ill patients. Methods: We studied 250 paired blood samples from 82 critically ill patients from a general intensive care unit by simultaneous POCT and central laboratory testing (Jaffé method). Correlation, precision, bias, and limits of agreement were assessed. Possible confounders for interference of noncreatinine chromogens were evaluated by multivariate linear regression analysis. Results: The mean difference in serum Cr measured by central laboratory and POCT was ++9.6 μmol/L (95%% limits of agreement: −11.2 to ++30.4 μmol/L). The mean percentage difference between the two techniques was 8.7%% (95%% limits of agreement −7.8%% to ++25.1%%). On multivariate regression, the difference in serum Cr was increased with greater hemoglobin and lactate levels but decreased with greater bilirubin, albumin, and calcium levels. Conclusions: Compared with the central laboratory testing, POCT-based measurement of serum Cr in critically ill patients carried a small negative bias. This difference appeared affected by the blood levels of biochemical variables known to affect the Jaffé method. POCT-based Cr measurement appears sufficiently accurate for clinical use. [ABSTRACT FROM AUTHOR]