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Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti‐inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID‐19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram‐negative bacteria‐induced sepsis. In a critically ill COVID‐19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID‐19. [ABSTRACT FROM AUTHOR]

Modern CRRT machines can deliver therapy that resembles IHD, and IHD treatments can be slowed to deliver therapy over 10-12 hours, which resembles CRRT. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators: Intensity of continuous renalreplacement therapy in critically ill patients. RRT was performed in 96.8% of accelerated-strategy patients and 61.8% of patients in the standard therapy patients, where RRT was discouraged unless conventional indications developed or AKI persisted for greater than 72 hours. Initially, dialysis nurses were consulted for ICU patients, but due to their high workload, they were often unable to respond in a timely manner to the increasing needs associated with a therapy that was delivered 24 hr/d in sicker and sicker patients. [Extracted from the article]

Objective Patients commonly receive i.v. fluids in the ED. It is still unclear whether the choice of i.v. fluids in this setting influences renal or patient outcomes. We aimed to assess the effects of restricting i.v. chloride administration in the ED on the incidence of acute kidney injury ( AKI). Methods We conducted a before-and-after trial with 5008 consecutive ED-treated hospital admissions in the control period and 5146 consecutive admissions in the intervention period. During the control period (18 February 2008 to 17 August 2008), patients received standard i.v. fluids. During the intervention period (18 February 2009 to 17 August 2009), we restricted all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes ( KDIGO) staging to define AKI. Results Stage 3 of KDIGO-defined AKI decreased from 54 (1.1%; 95% confidence interval [ CI] 0.8-1.4) to 30 (0.6%; 95% CI 0.4-0.8) ( P = 0.006). The rate of renal replacement therapy did not change, from 13 (0.3%; 95% CI 0.2-0.4) to 8 (0.2%; 95% CI 0.1-0.3) ( P = 0.25). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stage 3 (hazard ratio 1.82; 95% CI 1.13-2.95; P = 0.01). On sensitivity assessment after removing repeat admissions, KDIGO stage 3 remained significantly lower in the intervention period compared with the control period ( P = 0.01). Conclusion In a before-and-after trial, a chloride-restrictive strategy in an ED was associated with a significant decrease in the incidence of stage 3 of KDIGO-defined AKI. [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]

Objective: To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy.Design: Post hoc analysis of data from a multicenter, randomized, controlled trial.Setting: Thirty-five ICUs in Australia and New Zealand.Patients: Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study.Interventions: Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes.Measurements and Main Results: Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111 g/L; p < 0.001). Mean daily hemoglobin was 88 ± 7 and 99 ± 12 g/L in transfused and nontransfused patients. Among transfused patients, 228 (46.7%) had died by day 90 when compared with 426 (43.6%) of nontransfused patients (p = 0.27). Survivors received on average 316 ± 261 mL of RBC, whereas nonsurvivors received 302 ± 362 mL (p = 0.42). On multivariate Cox regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital.Conclusions: In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials. [ABSTRACT FROM AUTHOR]

Aim While patients with chronic kidney disease have reduced health-related quality of life ( HRQOL), long-term HRQOL of survivors of severe acute kidney injury ( AKI) remains unclear. Methods We analysed HRQOL from the Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy ( POST-RENAL) study and compared findings with those from a general Australian adult population enrolled in the Australian Diabetes, Obesity and Lifestyle ( Aus Diab) study. We used a multivariate analysis adjusted for baseline characteristics along with sensitivity analysis using age and sex-matched case controls. Results In the POST-RENAL study, 282 participants had HRQOL data collected using the SF-12 questionnaire. This was compared with 6330 participants from the Aus Diab study. Unadjusted analyses showed that POST-RENAL participants had lower physical component scores ( PCS, mean score 40.0 vs 49.8, P < 0.0001) and lower mental component scores ( MCS, mean score 49.8 vs 53.9, P < 0.0001) than the Aus Diab group. After age and sex matching, the difference in PCS and MCS remained statistically significant ( P < 0.0001). Advanced age, reduced renal function and albuminuria (all P ≤ 0.01) were all strongly associated with lower PCS values but not MCS values. After matching subsets of the cohorts on the basis of age, sex and renal function, PCS and MCS were lower in the POST-RENAL group ( P < 0.0001). Conclusion Survivors of severe AKI in the POST-RENAL study had lower physical and mental components of HRQOL compared with general population, even after adjustment for their reduced renal function. Increasing age and reduced renal function were associated with poorer physical QOL. [ABSTRACT FROM AUTHOR]

Purpose: In a previous study, restricting intravenous chloride administration in ICU patients decreased the incidence of acute kidney injury (AKI). To test the robustness of this finding, we extended our observation period to 12 months. Methods: The study extension included a 1-year control period (18 August 2007 to 17 August 2008) and a 1-year intervention period (18 February 2009 to 17 February 2010). During the extended control period, patients received standard intravenous fluids. During the extended intervention period, we continued to restrict all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes (KDIGO) staging to define AKI. Results: We studied 1,476 control and 1,518 intervention patients. Stages 2 and 3 of KDIGO defined AKI decreased from 302 (20.5 %; 95 % CI, 18.5-22.6 %) to 238 (15.7 %; 95 % CI, 13.9-17.6 %) ( P < 0.001) and the use of RRT from 144 (9.8 %; 95 % CI, 8.3-11.4 %) to 103 (6.8 %; 95 % CI, 5.6-8.2 %) ( P = 0.003). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stages 2 and 3 [hazard ratio 1.32 (95 % CI 1.11-1.58); P = 0.002] and use of RRT [hazard ratio 1.44 (95 % CI 1.10-1.88); P = 0.006]. However, on sensitivity assessment of each 6-month period, KDIGO stages 2 and 3 increased in the new extended intervention period compared with the original intervention period. Conclusions: On extended assessment, the overall impact of restricting chloride-rich fluids on AKI remained. However, sensitivity analysis suggested that other unidentified confounders may have also contributed to fluctuations in the incidence of AKI. [ABSTRACT FROM AUTHOR]

For many years, neutrophil gelatinase-associated lipocalin (NGAL) has been considered the most promising biomarker of acute kidney injury (AKI). Commercial assays and point-of-care instruments, now available in many hospitals, allow rapid NGAL measurements intended to guide the clinician in the management of patients with or at risk of AKI. However, these assays likely measure a mixture of different NGAL forms originating from different tissues. Systemic inflammation, commonly seen in critically ill patients, and several comorbidities contribute to the release of NGAL from haematopoietic and non-haematopoietic cells. The unpredictable release and complex nature of the molecule and the inability to specifically measure NGAL released by tubular cells have hampered its use a specific marker of AKI in heterogeneous critically ill populations. In this review, we describe the nature and cellular sources of NGAL, its biological role and diagnostic ability in AKI and the increasing concerns surrounding its diagnostic and clinical value. © 2014 S. Karger AG, Basel [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]

Aim Acute kidney injury ( AKI) is associated with increased mortality. While angiotensin-converting enzyme inhibitors ( ACEI) are known to slow progression of chronic kidney disease, their role in AKI remains unclear. Methods The Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy ( RENAL) study data were analysed according to ACEI use over time. The primary outcome was all-cause mortality at 90 days following randomisation. Analyses used a multivariate Cox model adjusted for either baseline or for time-dependent covariates, and a sensitivity analysis of patients surviving to at least the median time to ACEI initiation. Results Of the 1463 participants with available data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study data collection. Participants treated with ACEI were older ( P = 0.02) and had less sepsis at baseline ( P < 0.001). ACEI use was significantly associated with lower mortality at 90 days ( HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an increase in renal replacement therapy-free days ( P < 0.001), intensive care unit-free days ( P < 0.001) and hospital free-days ( P < 0.001) after adjusting for baseline covariates. Using the time-dependent analysis, however, the effect of ACEI administration was not significant ( HR 0.78, 95% CI 0.51-1.21, P = 0.3). The sensitivity analysis in day 8 survivors produced similar results. Conclusion In the RENAL study cohort, the use of ACEI during the study was not common and, after adjustment for time-dependent covariates, was not significantly associated with reductions in mortality. Further assessment of the effect of ACEI use in AKI patients is needed. [ABSTRACT FROM AUTHOR]

Objectives: To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury. The primary outcomes were all-cause mortality at 28 and 90 days. Design: Nested observational cohort study using data from the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study. Setting: Twenty-three ICUs in Australia and New Zealand. Patients: Four hundred thirty-nine critically ill patients with acute kidney injury Risk, Injury, Failure, Loss, End-stage kidney disease-injury (RIFLE-I) criteria. Interventions: None. Measurements and Main Results: The time between RIFLE-I acute kidney injury and randomization in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study (proxy for continuous renal replacement therapy commencement) was the variable of interest. All baseline variables in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study were assessed. Multivariable Cox, logistic, and linear regression models were used to assess the independent relationship of time of onset of RIFLE-I acute kidney injury and randomization and patient outcomes. The median time between RIFLE-I acute kidney injury and continuous renal replacement therapy commencement was 17.6 hours (interquartile range, 7.1-46 hr). Based on four groups of continuous renal replacement therapy commencement ([group 1; reference]: <7.1, [group 2]: ⩾ 7.1 to < 17.6, [group 3]: ⩾ 17.6 to < 46.0, [group 4]: ⩾ 46.0hr), earlier commencement of continuous renal replacement therapy was not associated with a significantly lower risk of death at 28 days (hazard ratio for group 2: 1.06, 95% Cl: 0.62-1.81; p = 0.83; hazard ratio for group 3: 1.23, 95% Cl: 0.71-2.12; p = 0.46; hazard ratio for group 4: 1.33, 95% Cl: 0.77- 2.31 ;p = 0.31). Similar findings were observed for death at 90 days. Conclusions: In a subgroup of participants of the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study, earlier commencement of continuous renal replacement therapy relative to RIFLE-I acute kidney injury was not significantly associated with improved survival. Additional studies with larger sample sizes and broader commencement times are warranted. [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]

The article discusses a study which aimed to examine the association between mean daily fluid balance and patient outcomes in the randomized evaluation of normal versus augmented level of replacement therapy trial. Results show that a negative fluid balance is associated with a decreased risk of death at 90 days. It concluded that fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

Background. A blood urea nitrogen (BUN)/creatinine ratio (BCR) >20 (0.081 in international unit) is used to distinguish pre-renal azotemia (PRA) and acute tubular necrosis (ATN). However, there is little evidence that BCR can distinguish between these two conditions and/or is clinically useful. Methods. We conducted a retrospective study using a large hospital database. Patients were divided into three groups: ‘low BCR’ (if BCR when acute kidney injury (AKI) developed was ≤20), ‘high BCR’ (if BCR when AKI developed was >20) and ‘no AKI’ if patients did not satisfy any of the Risk, Injury, Failure, Loss and End-stage kidney disease criteria for AKI during hospitalization. Results. Among 20 126 study patients, 3641 (18.1%) had AKI. Among these patients, 1704 (46.8%) had a BCR <20 at AKI diagnosis (‘low BCR’) and 1937 (53.2%) had a BCR >20 (‘high BCR’). The average BCR for the two groups was 15.8 versus 26.1 (P < 0.001). Hospital mortality was significantly less in the ‘low-BCR’ group (18.4 versus 29.9%, P < 0.001). Multivariable logistic regression analysis for hospital mortality (‘no AKI’ as a reference) showed that the odds ratio of ‘high BCR’ (5.73) was higher than that of ‘low BCR’ (3.32). Conclusions. Approximately half of the patients with AKI have a BCR >20, the traditional threshold of diagnosing PRA. Unlike PRA patients who have a lower mortality than ATN patients, high BCR patients had higher hospital mortality compared with low BCR patients, which was confirmed with multivariable analysis. These findings do not support BCR as a marker of PRA. [ABSTRACT FROM PUBLISHER]

Background. Acute kidney injury (AKI) after cardiac surgery is a common and serious condition carrying significant costs. During cardiopulmonary bypass (CPB) surgery, modifiable factors may contribute to post-operative AKI. Their avoidance might be a potential target for nephroprotection. Methods. The objective of the present study was to identify and determine whether intraoperative hypotension, anaemia, or their combination, red blood cell transfusion or vasopressor use are independent risk factors for post-operative AKI defined by the RIFLE (renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease) classification and other thresholds using a mixed logistic multivariate model. Results. We analysed 381 468 mean arterial pressure (MAP) measurements from 920 consecutive on-pump cardiac surgery patients. Overall, 19.5% developed AKI which was associated with an 8.2-fold increase in-hospital mortality. Haemoglobin concentration was an independent risk factor for AKI {odds ratio [OR] 1.16 per g/dL decrease [95% confidence interval (CI) 1.05–1.31]; P = 0.018} with systemic arterial oxygen saturation and pressure values not adding further strength to such an association. MAP alone or vasopressor administration was not independently associated with AKI but volume of red blood cell transfusion was, with its effect being apparent at a haemoglobin level of >8 g/dL (>5 mmol/L). In patients with severe anaemia (<25th percentile of lowest haemoglobin), the independent effect of hypotension (>75th percentile of area under the curve MAP <50 mmHg) on AKI was more pronounced [OR 3.36 (95% CI 1.34–8.41); P = 0.010]. Conclusion. Intraoperative avoidance of the extremes of anaemia, especially during severe hypotension and avoidance of transfusion in patients with haemoglobin levels >8 g/dL (>5 mmol/L) may help decrease AKI in patients undergoing cardiac surgery and represent targets for future controlled interventions. [ABSTRACT FROM PUBLISHER]

There is limited information on the incidence of acute kidney injury (AKI) in patients with traumatic brain injury (TBI) although AKI may contribute to morbidity and mortality. We investigated the incidence of AKI in patients with moderate and severe TBI and the association of AKI with risk factors and outcomes in these patients. We studied all TBI patients over 16 years of age admitted to the two designated trauma hospitals in the state of Victoria, Australia from 1 January to 31 December 2008. Patients were included if they had head trauma and presented with a Glasgow coma scale (GCS) <13. Prospectively collected data from the hospital trauma registries, ICUs, and pathology databases were analyzed retrospectively. Risk injury failure loss end (RIFLE) criteria were used to categorize renal function. The incidence of AKI was 9.2% (19/207). Patients who developed AKI were older, had higher severity of illness scores, and a lower GCS. Overall 42.1% of these patients died in hospital compared with 18.1% in patients without AKI. In univariable linear regression analysis, age, severity of illness, and admitting hospital were associated with AKI. After multivariable logistic regression, the occurrence of AKI was associated with age ( p < 0.001) and higher APACHE III scores ( p = 0.016). AKI is relatively common even in patients with TBI. Its association with age and APACHE III scores helps identify patients at higher risk of AKI. [ABSTRACT FROM AUTHOR]

Background.There are no suitably powered epidemiological studies of ‘transient azotaemia’ (TA). The objective of this study was to describe the epidemiology of TA and its independent association with hospital mortality. We hypothesized that TA would be associated with an independent increase in the risk of death. [ABSTRACT FROM PUBLISHER]

Cardiac surgery-associated acute kidney injury (AKI) is common and carries a poor prognosis. Hemodynamic and inflammatory factors and the release of labile iron, contributing to oxidation from reactive oxygen species are among the major determinants of cardiac surgery-associated AKI. The diagnosis of AKI is typically delayed because of the limitations of currently used clinical biomarkers indicating loss of renal function. However, several novel renal biomarkers, which predict AKI or protection from AKI after cardiopulmonary bypass (CPB), have been identified as early markers of kidney injury. In this state-of-the-art review, the authors analyze the pathophysiological implications of recent findings regarding novel renal biomarkers in relation to CPB-associated AKI. Neutrophil gelatinase–associated lipocalin, liver-type fatty acid-binding protein, and alpha-1 microglobulin predict the development of CPB-associated AKI, while hepcidin isoforms appear to predict protection from it, and these biomarkers are involved in iron metabolism. Neutrophil gelatinase-associated lipocalin participates in local iron transport. Liver-type fatty acid–binding protein and alpha-1 microglobulin function as high-affinity heme-binding proteins in different species, while hepcidin is central to iron sequestration and when increased in the urine appears to protect from CPB-associated AKI. Free iron-related, reactive oxygen species–mediated kidney injury appears to be the unifying pathophysiological connection for these biomarkers. Such novel findings on renal tubular biomarkers were further combined with other lines of evidence related to hemolysis during CPB, the associated excess of free heme and iron, knowledge of the effect of free iron on renal tubular cells, and recent trial evidence targeting free iron-mediated mechanisms of AKI. Novel biomarkers point toward free iron-mediated toxicity to be an important mechanism of AKI in patients receiving cardiac surgery with CPB. [Copyright &y& Elsevier]

Background. In adult cardiac surgery, the predictive value for AKI of neutrophil gelatinase-associated lipocalin (NGAL) appears to have wide variability. The choice of definition of acute kidney injury (AKI) might, at least in part, account for such variability. [ABSTRACT FROM PUBLISHER]

The article reports on a study of the value of novel and conventional serum biomarkers in predicting acute kidney injury (AKI) among adult cardiac surgical patients. It examined concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL) serum cystatin C, creatinine, and urea of 100 cardiac surgical patients. It showed that plasma NGAL and serum cystatin C were conventional biomarkers which are good in identifying patients who developed AKI after cardiac surgery.

Changes in urine output and glomerular filtration rate are neither necessary nor sufficient for the diagnosis of renal pathology. Yet no simple alternative for the diagnosis currently exists. Until recently, there has been no consensus as to diagnostic criteria or clinical definition of acute renal failure. Depending on the definition used, acute renal failure has been reported to affect from 1 to 25% of ICU patients and has led to mortality rates from 15 to 60%. The RIFLE criteria were developed to standardize the diagnosis of acute renal failure and in the process the term acute kidney injury (AKI) has been proposed to encompass the entire spectrum of the syndrome from minor changes in renal function to requirement for renal replacement therapy. Thus, AKI is not acute renal failure but a more general description. Small changes in kidney function in hospitalized patients are important and are associated with significant changes in short and possibly long-term outcomes. The RIFLE criteria provide a uniform definition of AKI and have now been validated in numerous studies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses the treatment options for intensive care unit (ICU) patients with oliguric acute kidney injury (AKI). Some of the therapeutic options for oliguric AKI patients include optimization of systemic hemodynamics, added fluid therapy, loop diuretics administration and renal replacement therapy. However, several studies reveal that loop diuretics administration can be potentially detrimental for AKI patients.

Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions. [ABSTRACT FROM AUTHOR]

Perioperative hypotension is common and associated with poor outcomes, including acute kidney injury (AKI). The mechanistic link between perioperative hypotension and AKI is at least partly a consequence of the susceptibility of the kidney, and particularly the renal medulla, to ischaemia and hypoxia. Several critical gaps in our knowledge lead to uncertainty about when and how to intervene to prevent AKI attributable to perioperative hypotension. First, although we know that the risk of AKI varies with both the severity and duration of hypotensive episodes, 'safe' levels of arterial pressure have not been identified. Second, there have been few adequately powered clinical trials of interventions to avoid perioperative hypotension. Thus, most evidence surrounding perioperative hypotension is observational rather than based on randomised clinical trials. This means that the link between perioperative hypotension and AKI may represent association (where both phenomena reflect illness severity) rather than causation. Third, there is little information regarding the relative risks and benefits of various clinically available therapies (e.g. vasoconstrictors, i.v. fluids, or both) to treat and prevent perioperative hypotension, particularly with regard to renal medullary perfusion and oxygenation. Fourth, there are currently no validated, clinically feasible methods for real-time clinical monitoring of renal perfusion or oxygenation. Thus, future developments in perioperative kidney-protective strategies must rely on the development of methods to better monitor renal perfusion and oxygenation in the perioperative period, and thereby guide timing, intensity, type, and duration of interventions. [ABSTRACT FROM AUTHOR]

Introduction: In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. Methods: We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first 7 days of treatment. Results: We studied 1,616 patients from three tertiary intensive care units (ICUs) in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 h and remained negative over 7 days to a mean nadir of −4.1 L (95% confidence interval (CI) of −4.6 to −3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (−67.7 mL/h; standard deviation (SD): 75.7); however, residual urine output (−34.7 mL/h; SD: 54.5), crystalloid administration (48.1 mL/h; SD: 44.6), and nutritional input (36.4 mL/h; SD: 29.7) significantly contributed to FB. Patients with a positive FB after 72 h of CRRT were more severely ill, required high-dose vasopressors, and had high lactate concentrations (5.0 mmol/L; interquartile range: 2.3–10.5). A positive FB was independently associated with increased hospital mortality (odds ratio: 1.70; 95% CI; p = 0.004). Conclusion: In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 h had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult. [ABSTRACT FROM AUTHOR]

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2) by near‐infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2), and, in some protocols, brain tissue PO2, by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2, rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg−1 min−1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose‐dependently decreased rSO2, but increased renal cortical and medullary PO2. Increasing blood haemoglobin concentration increased rSO2, but not renal PO2. We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation. [ABSTRACT FROM AUTHOR]

Introduction: Continuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality. Methods: We studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h. Results: We studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46–1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00–1.20 mL/kg/h, 1.21–1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13–1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness. Conclusion: Early UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. Results: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21–3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. Results: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. Conclusion: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified. [ABSTRACT FROM AUTHOR]

Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1–3) days vs. 3 (Q1-Q3, 1–6) days) and hospital length of stay (median 14 (Q1-Q3, 9–24) days vs. 10 (Q1-Q3, 7–17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide. [ABSTRACT FROM AUTHOR]

Introduction: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. Methods: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. Results: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5–16] vs. 8 [5–15] days; adjusted median difference, 0.65 [95% CI, −0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). Conclusions: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation. [ABSTRACT FROM AUTHOR]

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]

Aim: Acute kidney injury (AKI) is associated with poor short‐term and long‐term clinical outcomes. The role of nephrology follow‐up in post‐AKI management remains uncertain. Methods: A systematic review and meta‐analysis were performed examining all randomized controlled trials and observational studies assessing the effect of nephrology follow‐up on patients' clinical outcomes. The primary outcome was all‐cause mortality. The secondary outcomes were renal outcomes, which were defined as a composite of requirement of permanent dialysis and recurrent AKI. Pooled analysis was performed using a random‐effect model. Results: We identified six studies (8972 patients, mean follow‐up of 49 months). Five were retrospective cohort studies and one was a prospective cohort study. Risk of bias was a concern with all studied. Only four studies reported primary and/or secondary outcomes and were included. Compared with patients without nephrology follow‐up, patients with nephrology follow‐up had significantly reduced mortality by 22% (three studies, 3240 patients, relative risk [RR] = 0.78, 95% confidence interval [CI] = 0.70‐0.88, I2 = 0.0%). Nephrology follow‐up did not improve composite renal outcomes with high heterogeneity due to significant differences in reported renal outcomes and follow‐up period (two studies, 2537 patients, RR = 1.72, 95% CI = 0.49‐6.05, I2 = 90.1%). Conclusion: Current evidence from observational studies is biased. It suggests long‐term survival benefits with post‐discharge nephrology follow‐up in AKI patients. However, due to its low quality, such evidence is only hypothesis‐generating. Nonetheless, it provides a rationale for future randomized controlled trials of nephrology follow‐up in AKI patients. SUMMARY AT A GLANCE: The present meta‐analysis assessed the effect of nephrology follow‐up on patients' clinical outcomes, and suggested long‐term survival benefits in acute kidney injury (AKI) survivors. Although the study inherently comprises potential risks of bias due to paucity of available data, the results provide a rationale for future randomized controlled trials. [ABSTRACT FROM AUTHOR]

The author reflects on the study by P. Jia and colleagues on the role of xenon on septic acute kidney injury. The study reportedly involved mice which were treated with xenon or nitrogen before sepsis was inducted by injecting Escherichia coli lipopolysaccharide (LPS). The results revealed that xenon can regulate miR-21 expression in kidneys.

Background: Mortality in intensive care unit (ICU) patients with acute kidney injury (AKI) remains high. Previous studies have explored the role of HMG‐CoA reductase inhibitors (statins) with variable findings. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Study recruited 1508 participants requiring dialysis in ICU between 2006 and 2009. Statin use was recorded at study baseline. Multivariate Cox modelling was used to assess associations of such statin use and all‐cause mortality. Propensity score analysis was performed for sensitivity analysis. The primary outcome was all‐cause mortality at 90 days. Results: Of the 1462 participants with the available data on statin usage, 187 (12.8%) received statin therapy at baseline. Participants who receiving statins were older (P < 0.001), less likely to have sepsis or require mechanical ventilation (P < 0.001). Multivariable analysis showed statin use did not have significant associations with mortality at both day 28 (hazard ratio (HR) = 1.053, 95% confidence interval (CI) = 0.784–1.415, P = 0.730) and day 90 (HR = 1.091, 95% CI = 0.836–1.424, P = 0.520). Propensity score analysis confirmed the lack of association between statin use and mortality at day 90 (HR = 1.042, 95% CI = 0.734–1.479, P = 0.819). However, in septic patients, multivariable analysis suggested statin therapy was associated with a trend to higher mortality at day 90 (HR = 1.688, 95% CI = 1.132–2.519, P = 0.010) and continuation of statins was associated with higher mortality (HR = 2.160, 95% CI = 1.296–3.599, P = 0.003), compared with statin withdrawal. Conclusion: In the RENAL study cohort, baseline statin use was not associated with mortality. Our findings do not support a protective role of statins in ICU patients with severe AKI. Clinical Trials registration number for the RENAL study: NCT00221013, the date of registration: September 14, 2005. SUMMARY AT A GLANCE: Among 1,462 patients requiring dialysis in the intensive care unit (ICU) between 2006 and 2009, there was no association between statin therapy and mortality. However, among patients with septic acute kidney injury (AKI) requiring dialysis, baseline statin use correlates with increased mortality. These findings do not support a protective role of statins in ICU patients with severe AKI, but raise caution about statin use among patients with septic AKI. [ABSTRACT FROM AUTHOR]

Aim: Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti‐inflammatory drug, tempol, may modify these responses. Methods: Following unilateral nephrectomy, we inserted renal arterial catheters and laser‐Doppler/oxygen‐sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg−1 h−1), renal arterial tempol (RAT; 3 mg kg−1 h−1), or vehicle. Results: Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min−1). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3‐nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor‐erythroid‐related factor‐2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis‐induced overexpression of cortical tissue tumor necrosis factor alpha (TNF‐α; 51 ± 16% decrease; p = 0.003) and medullary Thr‐495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015). Conclusions: In ovine Gram‐negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF‐α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram‐negative sepsis. [ABSTRACT FROM AUTHOR]

Purpose: The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI. Methods: This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition. Results: Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1–1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32–0.36) for mortality. Conclusion: SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria. [ABSTRACT FROM AUTHOR]

Background: The association between intraoperative oliguria during major abdominal surgery and the subsequent development of postoperative acute kidney injury (AKI) remains poorly defined. We hypothesised that, in such patients, intraoperative oliguria would be an independent predictor of subsequent AKI.Methods: We performed a post hoc analysis of data from the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial of conservative vs liberal fluid therapy during and after major abdominal surgery. We used χ2, logistic regression, and fractional polynomials to study the association between intraoperative oliguria defined as a urinary output <0.5 ml kg-1 h-1 and the development of postoperative AKI defined by the Kidney Disease Improving Global Outcomes consensus criteria.Results: We included 2444 of 2983 patients from the RELIEF trial in this study. A total of 889 patients (36%) met oliguric criteria intraoperatively. Oliguria occurred in 35% of those without AKI, and 44%, 48%, and 45% of those who developed postoperative AKI Stages 1-3, respectively (P<0.001 for trend). Intraoperative oliguria was associated with an increased risk of AKI, risk ratio: 1.38 (95% confidence interval: 1.14-1.44; P<0.001), but greater intensity of oliguria (urine output <0.3 ml kg-1 h-1) did not increase this risk further. Most patients with oliguria did not develop AKI; the positive predictive value of oliguria was 25.5%, and the negative predictive value was 81.6%.Conclusions: Intraoperative oliguria, defined as urine output <0.5 ml kg-1 h-1, was relatively common and was associated with postoperative AKI. However, the predictive utility of oliguria for AKI was low, whilst its absence had a good predictive value for an AKI-free postoperative course.Clinical Trial Registration: NCT01424150. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prognostic value of baseline SOFA coagulation score (SOFA‐CS) and change in platelet counts in patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Methods: We performed a secondary analysis from the Randomized Evaluation of Normal versus Augmented Level of RRT (RENAL) study. The primary endpoint was all‐cause mortality at 90 days after randomization. The association between baseline SOFA‐CS, changes in platelet counts, process of care, and clinical outcomes were analyzed using multivariate Cox model adjusted for baseline variables. Results: The complete SOFA‐CS data were available in 1454 out of 1508 patients from the RENAL study. Among them, 708 patients had an abnormal SOFA‐CS (defined as SOFA‐CS ≥ 1), while 746 patients had normal SOFA‐CS at baseline (SOFA‐CS = 0). An abnormal SOFA‐CS was independently associated with an increased risk of death at 90 days (HR = 1.27, 95% CI = 1.05–1.53, P = 0.015). An abnormal SOFA‐CS was associated with prolonged length of ICU stay and duration of mechanical ventilation as well. Furthermore, there was no significant association between changes in platelet counts in patients who survived beyond 4 days and 90 day mortality (HR = 1.26, 95% CI = 0.29–5.56, P = 0.76). However, on multivariable analysis a decline of ≥60% (HR = 1.93, 95% CI = 1.23–3.05, P = 0.004) was associated with 90 day mortality in patients who survived beyond the first 4 days. Conclusions: In the RENAL study, thrombocytopaenia is a common phenomenon in patients with severe AKI receiving CRRT. An abnormal baseline SOFA‐CS and reductions in platelet counts were associated with increased mortality at 90 days. Summary at a Glance: A secondary analysis of prospectively collected data from the RENAL study confirmed that an abnormal baseline SOFA CS (sequential organ failure assessment coagulation score), based on a reduced platelet count, was associated with increased 90‐day mortality in AKI patients on CRRT. [ABSTRACT FROM AUTHOR]

Introduction: The effect of continuous renal replacement therapy (CRRT) on renal function is poorly understood. However, the initiation of CRRT may induce oliguria. We aimed to investigate the impact of CRRT commencement on urine output (UO). Methods: This was a retrospective cohort study in two intensive care units. We included all patients who underwent CRRT and collected data on hourly UO and fluid balance before and after CRRT commencement. We performed an interrupted time series analysis using segmented regression to assess the relationship between CRRT commencement and UO. Results: We studied 1,057 patients. Median age was 60.7 years (interquartile range [IQR], 48.3–70.6), and the median APACHE III was 95 (IQR, 76–115). Median time to CRRT was 17 h (IQR, 5–49). With start of CRRT, the absolute difference in mean hourly UO and mean hourly fluid balance was −27.0 mL/h (95% CI: −32.1 to −21.8; p value < 0.01) and – 129.3 mL/h (95% CI: −169.2 to −133.3), respectively. When controlling for pre-CRRT temporal trends and patient characteristics, there was a rapid post-initiation decrease in UO (−0.12 mL/kg/h; 95% CI: −0.17 to −0.08; p value < 0.01) and fluid balance (−78.1 mL/h; 95% CI: −87.9 to −68.3; p value < 0.01), which was sustained over the first 24 h of CRRT. Change in UO and fluid balance were only weakly correlated (r −0.29; 95% CI: −0.35 to −0.23; p value < 0.01). Conclusion: Commencement of CRRT was associated with a significant decrease in UO that could not be explained by extracorporeal fluid removal. [ABSTRACT FROM AUTHOR]

Introduction: Treatment with continuous renal replacement therapy (CRRT) is common during extracorporeal membrane oxygenation (ECMO). Such ECMO-CRRT has specific technical characteristics, which may affect circuit life. Accordingly, we studied CRRT haemodynamics and circuit life during ECMO. Methods: ECMO and non-ECMO-CRRT treatments in two adult intensive care units were compared using data collected over a 3-year period. A potential predictor of circuit survival identified in a 60% training data subset as a time-varying covariate within a Cox proportional hazard model was subsequently assessed in the complementary remaining data (40%). Results: Median [interquartile range] CRRT circuit life was greater when associated with ECMO (28.8 [14.0–65.2] vs. 20.2 [9.8–40.2] h, p < 0.0001). Access, return, prefilter, and effluent pressures were also greater during ECMO. Higher ECMO flows were associated with higher access and return pressures. Classification and regression tree analysis identified an association between high access pressures and accelerated circuit failure, while both first access pressures ≥190 mm Hg (HR 1.58 [1.09–2.30]) and patient weight (HR 1.85 [1.15–2.97] third tertile vs. first tertile) were independently associated with circuit failure in a multivariable Cox model. Access dysfunction was associated with a stepwise increase in transfilter pressure, suggesting a potential mechanism of membrane injury. Conclusion: CRRT circuits used in conjunction with ECMO have a longer circuit life than usual CRRT despite exposure to higher circuit pressures. Markedly elevated access pressures, however, may predict early CRRT circuit failure during ECMO, possibly via progressive membrane thrombosis as evidenced by increased transfilter pressure gradients. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate patients' characteristics, fluid and hemodynamic management, and outcomes according to the severity of cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: In a single-center, prospective cohort study, we enrolled 282 adult cardiac surgical patients. In a secondary analysis, we assessed preoperative patients' characteristics, physiological variables, and medication for intra- and postoperative fluid and hemodynamic management and outcomes according to CSA-AKI stages by the Renal risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification. Variables of fluid and hemodynamic management were further assessed with regard to the need for postoperative renal replacement therapy (RRT) and in-hospital mortality by the area under the curve for the receiver operating characteristic (AUC-ROC) and multivariate regression analysis. Results: Patients with worsening RIFLE stage, were significantly older, had lower estimated glomerular filtration rate and higher body mass index, more peripheral vascular and chronic obstructive pulmonary disease, atrial fibrillation, and prolonged duration of cardiopulmonary bypass (all p < 0.01). Patients with more severe AKI stage stayed longer in the intensive care and hospital, had higher in-hospital mortality, and requirement for RRT (all p < 0.001). Also, with worsening RIFLE stage, patients had lower intraoperative mean arterial pressure (MAP); p = 0.047, despite higher doses of norepinephrine (p < 0.001). The intraoperative MAP showed the best discriminatory ability (AUCROC: >0.8) for and was independently associated with RRT and in-hospital mortality. Moreover, with increasing AKI severity, patients received significantly more fluid infusion, and required higher dose of furosemide; nonetheless, they had increased postoperative fluid balance. Conclusions: In this cohort, reduced MAP and increased fluid balance were independently associated with increased mortality and need for RRT after cardiac surgery. [ABSTRACT FROM AUTHOR]

Aim: To study the associations between baseline blood glucose levels (BGL), glycemic variability and clinical outcomes in patients with severe acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). Methods: We performed a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level of RRT (RENAL) study. A multivariate Cox regression model was used to assess the association between baseline BGL, glycemic variability and clinical outcomes. The primary outcome was all-cause mortality, and secondary outcomes were duration of hospital and intensive care unit (ICU) stay. Results: Baseline BGL data were available in 1404 out of 1508 patients from the RENAL study. Among them, 627 patients died within 90 days of randomization. Compared to patients in the second quartile (BGL 5.8–7.2 mmol/L), patients in the first quartile (BGL < 5.8 mmol/L) had increased mortality rate (90-day HR 1.48; p = 0.001; 28-day HR 1.47; p = 0.042). However, there were no significant differences in ICU and hospital length of stay (LOS) (p = 0.82 and p = 0.33, respectively). Glycemic variability data were from 1345 out of 1404 patients who had data for BG values within 28 days. Higher coefficient of variation (CV) (HR 1.02; P trend = 0.002) and standard deviation value (SD) (HR 1.29; P trend = 0.027) were associated with higher risk of death at day 90. Conclusions: We identified a low BGL within the normal physiological range at baseline and greater CV and SD values as significant modifiable risk factors for mortality in severe AKI patients in ICU, which may be a target for intervention. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. Methods: This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m2. 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 effect of RRT initiation strategy on outcomes by CKD status. Results: We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114–160) and 76 (64–90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79–1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05–3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41–7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34–1.47, p value for interaction, 0.009). Conclusion: In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD. [ABSTRACT FROM AUTHOR]

Background: Nephrocheck® was approved for acute kidney injury (AKI) risk assessment in critically illness. However, new studies suggest that urinary concentration affects Nephrocheck® and previous studies did not provide data on urinary output (UO) at the time of measurement. Methods: We performed a prospective cohort study of the Nephrocheck® in intensive care unit patients fulfilling standard inclusion criteria. The primary outcome was Stage 2 or 3 AKI defined by both UO and creatinine Kidney Disease Improving Global Outcomes (KDIGO) criteria in the subsequent 12 h. The secondary outcome was the relationship of UO with Nephrocheck® measurement. Results: Among 98 patients, the primary outcome occurred in 53 (54.1%) overall, but in 23 (23.5%) by creatinine criteria alone. The median (interquartile range) Nephrocheck® in patients with subsequent Stage 2 or 3 AKI was greater than in Stage 1 or no‐AKI patients (0.97 [0.48–1.99] vs. 0.46 [0.22–1.17]; p =.005). However, its area under the receiver characteristic curve was 0.66 (95% confidence interval [CI], 0.56–0.77). Moreover, Nephrocheck® was significantly and inversely correlated with UO (ρ = −.46, p <.001) at the time of measurement and, on a multivariable logistic regression, Nephrocheck® was not associated with subsequent Stage 2 or 3 AKI (OR 1.06 [95% CI, 0.74–1.53], p =.73). In contrast, the UO had an OR of 0.98 for each ml/h increase (95% CI, 0.97–1.00, p =.007). Conclusion: Nephrocheck®'s predictive performance was limited and its value was inversely correlated with UO. Nephrocheck® had no independent relationship with outcome once UO at measurement was considered. [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: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. Methods: We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. Results: In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean ± SEM) 52 ± 4 to 41 ±5 mmHg simultaneously with reduced arterial pressure (from 108 ± 5 to 88 ± 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 ± 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 ±6 mmHg within 20–30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 ± 1 mmHg and mean arterial pressure fell by 7 ± 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 ± 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. Conclusions: Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration. [ABSTRACT FROM AUTHOR]

Purpose: Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients. Methods: The Acute Kidney Injury-Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge. Results: A total of 1032 ICU patients out of 1802 [57.3 %; 95 % confidence interval (CI) 55.0-59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95 % CI 0.890-3.169; p = 0.109), stage 2 = 2.945 (95 % CI 1.382-6.276; p = 0.005), and stage 3 = 6.884 (95 % CI 3.876-12.228; p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m in 47.7 % (95 % CI 43.6-51.7) versus 14.8 % (95 % CI 11.9-18.2) in those without AKI, p < 0.001. Conclusions: This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions. [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]