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Objectives: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant., Design: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722)., Setting: One hundred-fifty-three ICUs in 13 countries., Patients: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ)., Interventions: None., Measurements and Main Results: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ ( p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ ( p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ ( p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU ( p < 0.001) and hospital discharge ( p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007)., Conclusions: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood., Design: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF., Setting: All liver transplant ICUs across Australia and New Zealand., Participants: Sixty-two patients with ALF., Main Outcome Measures: Impact of CRRT on hyperammonaemia and patient outcomes., Results: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 μmol/L (interquartile range [IQR], 91-172), median creatinine was 165 μmol/L (IQR, 92-263) and median urea was 6.9 mmol/L (IQR, 3.1-12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2-12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 μmol/L [IQR, 102-198] v 91 μmol/L [IQR, 54-115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 μmol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05)., Conclusion: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.

Importance: Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear., Objective: To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration., Design, Setting, and Participants: The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019., Exposures: Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight., Main Outcomes and Measures: Risk-adjusted 90-day survival., Results: Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (β = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08)., Conclusions and Relevance: Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings., Trial Registration: ClinicalTrials.gov identifier: NCT00221013.

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 χ 2 , 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., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

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]: ≥ 46.0 hr), 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% CI: 0.62-1.81; p = 0.83; hazard ratio for group 3: 1.23, 95% CI: 0.71-2.12; p = 0.46; hazard ratio for group 4: 1.33, 95% CI: 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.

Background: The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI., Methods and Findings: We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration., Conclusions: Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis., Trial Registration: www.ClinicalTrials.govNCT00221013.

Background: In the field of critical care nephrology, recent publications have used different illness severity scoring systems, making outcome comparisons difficult., Objective: To establish a methodology to translate one illness severity scoring system into another for critically ill patients with acute kidney injury (AKI)., Design: Statistical analysis of prospectively obtained data., Methods: Using data from the Australian and New Zealand Intensive Care Society Adult Patient Database, we obtained Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III and Simplified Acute Physiology Score (SAPS II) scores for all patients admitted with AKI. We applied correlation and linear regression analyses as well as cross validation with hold out samples., Results: Between 2001 and 2010, the three illness severity scores were obtained in 636 431 admissions. Of these, 37 203 fulfilled the APACHE score criteria for AKI. The coefficient of determination (R2) between APACHE II and APACHE III scores was 0.66. The overall model was APACHE III = 3.13 ? APACHE II + 7.99 (P < 0.001). Similarly, the R2 between APACHE III and the SAPS II scores was 0.78. The overall model was APACHE III = 1.49 ? SAPS II + 15.5 (P < 0.001). The R2 between APACHE II and SAPS II scores was 0.62. The overall model was APACHE II = 0.35 ? SAPS II + 9.3 (P < 0.001)., Conclusions: Simple, robust translational formulae can be developed to allow clinicians to compare illness severity of patients with AKI when illness severity is expressed with different scoring systems.

Objective: We aim to evaluate the incidence and outcome of acute kidney injury (AKI) among critically ill adult patients with H1N1 2009 infection., Design and Patients: From a prospectively collected influenza A (H1N1) 2009 bi-national, we identified 671 adult patients admitted to intensive care unit (ICU) from June 1 to August 31, 2009. Of these, 628 (93.6%) had admission and/or peak serum creatinine values during ICU stay. We defined AKI according to the creatinine criteria of the RIFLE classification., Results: Of 628 adult patients, 211 [33.6%, 95% confidence interval (CI) 29.8-37.4%] had AKI: 41 (6.5%) risk, 56 (8.9%) injury and 114 (18.2%) failure. Of all 211 AKI patients, 76 [36.0% (29.4-42.6%)] died in hospital (36.6% in risk, 25.0% in injury and 41.3% in failure group) compared with 33 of 408 (8.1%) patients without AKI. Among the 33 AKI patients treated with renal replacement therapy, 13 died (39.4%). Mechanical ventilation [odds ratio (OR) 3.62 (2.07-6.34)], any severe co-morbidity (OR 2.36, 95% CI 1.15-3.71), age (OR 1.02, 95% CI 1.01-1.03 per 1 year increase), and AKI (OR 6.69, 95% CI 4.25-10.55) were independently associated with hospital mortality., Conclusions: Acute kidney injury appears common in H1N1 2009 infected patients and is independently associated with an increased risk of hospital mortality.

The year 2009 was characterized by a pandemic with a new virus, the 2009 H1N1 influenza virus. This pandemic was responsible for thousands of deaths worldwide, many more hospital admissions, and thousands of admissions to intensive care units (ICUs). Among those admitted to ICUs, the pandemic was associated with a mortality of approximately 16%, a high incidence of acute lung injury and, in some cases, acute respiratory distress syndrome severe enough to require support with extracorporeal membrane oxygenation. As part of such a critical illness, a percentage of patients developed acute kidney injury (AKI) which complicated their clinical course and, in some patients, required support by renal replacement therapy. In a case series from Mexico, the incidence of severe AKI was reported in about 30% of the patients. Similarly, at the Austin Hospital, of 13 cases, 8 developed AKI with 3 being classified in the failure category of the RIFLE classification. Among the patients with AKI, hospital mortality was approximately 25%. Of the AKI patients, 3 (37.5%) received renal replacement therapy and, among these, 1 died. In a case of severe AKI and multi-organ failure from whom histological material was obtained, the renal histopathological findings were typical of acute tubular necrosis. One patient who suffered from hypoxic brain injury due to cardiac arrest at home secondary to H1N1 pneumonia became a kidney and liver donor. There was no evidence of viral infiltration on kidney biopsy and the recipient did not develop H1N1 infection., (2010 S. Karger AG, Basel.)

Introduction: We conducted a study to evaluate the incidence, risk factors and outcomes associated with early acute kidney injury (AKI) in sepsis., Methods: The study was a retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were collected from 57 intensive care units (ICUs) across Australia. In total, 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis. The main outcome measures were clinical and laboratory data and outcomes., Results: Of 120,123 patients admitted, 33,375 had a sepsis-related diagnosis (27.8%). Among septic patients, 14,039 (42.1%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI. For septic AKI stratified by RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease) category, 38.5% of patients belonged to the risk category, 38.8% to the injury category and 22.7% to the failure category. Septic AKI patients had greater acuity of illness (P < 0.0001), lower blood pressure (P < 0.0001), higher heart rates (P < 0.0001), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P < 0.0001), greater acidaemia (P < 0.0001) and higher white cell counts (P < 0.0001) compared with patients with nonseptic AKI. Septic AKI was also associated with greater severity of AKI (RIFLE category injury or failure) compared with nonseptic AKI. Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU (19.8% versus 13.4%; odds ratio 1.60, 95% confidence interval 1.5 to 1.7; P < 0.001) and in hospital (29.7% versus 21.6%; odds ratio 1.53, 95% confidence interval 1.46 to 1.60; P < 0.001) compared with nonseptic AKI. Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories. Septic AKI patients had longer durations of stay in both ICU and hospital across all strata of RIFLE categories., Conclusion: Septic AKI is common during the first 24 hours after ICU admission. Patients with septic AKI are generally sicker, with a higher burden of illness, and have greater abnormalities in acute physiology compared with patients with nonseptic AKI. Moreover, septic AKI is independently associated with higher odds of death and longer duration of hospitalization.

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

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]