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PURPOSE: The best renal replacement therapy (RRT) modality remains controversial. We compared mortality and short- and long-term renal recovery between patients treated with continuous RRT and intermittent hemodialysis. METHODS: Patients of the prospective observational multicenter cohort database OUTCOMEREA were included if they underwent at least one RRT session between 2004 and 2014. Differences in patients' baseline and daily characteristics between treatment groups were taken into account by using a marginal structural Cox model, allowing one to substantially reduce the bias resulting from confounding factors in observational longitudinal data analysis. The composite primary endpoint was 30-day mortality and dialysis dependency. RESULTS: Among 1360 included patients with RRT, 544 (40.0 %) and 816 (60.0 %) were initially treated by continuous RRT and intermittent hemodialysis, respectively. At day 30, 39.6 % patients were dead. Among survivors, 23.8 % still required RRT. There was no difference between groups for the primary endpoint in global population (HR 1.00, 95 % CI 0.77-1.29; p = 0.97). In patients with higher weight gain at RRT initiation, mortality and dialysis dependency were significantly lower with continuous RRT (HR 0.54, 95 % CI 0.29-0.99; p = 0.05). Conversely, this technique appeared to be deleterious in patients without shock (HR 2.24, 95 % CI 1.24-4.04; p = 0.01). Six-month mortality and persistent renal dysfunction were not influenced by the RRT modality in patients with dialysis dependence at ICU discharge. CONCLUSION: Continuous RRT did not appear to improve 30-day and 6-month patient outcomes. It seems beneficial for patients with fluid overload, but might be deleterious in the absence of hemodynamic failure.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear. To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration. 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. Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight. Risk-adjusted 90-day survival. 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). 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. ClinicalTrials.gov identifier: NCT00221013.

Background The KDIGO recommendation in acute kidney injury (AKI) patients requiring kidney replacement therapy is to deliver a Urea Kt/V of 1.3 for intermittent thrice weekly hemodialysis, and an effluent volume of 20–25 ml/kg/hour when using continuous renal replacement therapy (CRRT). Considering that prior studies have suggested equivalent outcomes when using CRRT-prolonged intermittent renal replacement therapy (PIRRT) effluent doses below 20 mL/kg/h, our group investigated the possible benefits of low effluent volume CRRT-PIRRT (12.5 ml/Kg/hour). Methods Thirty-six AKI patients that had been treated in the previous 12 months by CRRT-PIRRT with low effluent volume were included in the present retrospective observational study. The total effluent volume, derived from the formula [25 (or 12.5 ml) × kg body weight × 24], was administered over 24 h in CRRT and over 10 h in daily PIRRT. The control group consisted of the last 36 AKI patients previously treated with standard effluent volume CRRT (25 ml/kg/hour). Mortality within 90 days, shift from low effluent volume to standard effluent volume due to dialysis inadequacy, and remission of AKI were the end points. The two groups were homogeneous for age, sex, and sequential organ failure assessment (SOFA) score. Patients with AKI caused by metformin-induced lactic acidosis were excluded because they were treated with standard effluent volume CRRT until the lactic acidosis was corrected by subsequently reducing the effluent volume to 12.5 ml/kg/hour. Results The two groups were homogeneous as for baseline features. The UKt/V in the low effluent volume group was 0.51 ± 0.04 in CRRT and 0.50 ± 0.07 in PIRRT per session (Table 3 ). The UKt/V in the standard effluent volume group was 1.00 ± 0.02 in CRRT and 0.95 ± 0.05 in PIRRT per session. No differences were observed between the 2 groups regarding death from any cause at 90 days, and recovery of renal function. No patient was switched from low effluent volume to standard effluent volume due to inadequate control of uremic toxins. Serum creatinine at discharge from the hospital in patients with no KRT dependence was 2.1 ± 0.6 mg/dl in standard effluent volume and 1.9 ± 0.5 in low effluent volume ( p  = 0.37). All low effluent volume patients showed adequate metabolic, electrolyte, and acid–base profile control. In the low effluent volume group, the incidence of hypophosphatemia was lower than in the standard effluent volume group (5 vs 15, p  = 0.003). Conclusions In this single-center retrospective study, low effluent volume CRRT-PIRRT was associated with similar outcomes to standard effluent volume CRRT-PIRRT, which is consistent with the results of prior observational studies. Randomized controlled studies comparing low effluent volume with standard effluent volume are needed. Graphical abstract

Abstract Background Acute kidney injury (AKI) is frequent among intensive care unit (ICU) patients and is linked with high morbidity and mortality. In the absence of specific pharmacological treatments for AKI, continuous renal replacement therapy (CRRT) is a primary treatment option. This study aimed to develop and validate a predictive model for 90-day mortality in critically ill patients with AKI undergoing CRRT. Methods Clinical data from DATADRYAD were used. We randomly divided 1121 adult patients receiving CRRT for AKI into training (80%, n = 897) and validation (20%, n = 224) cohorts. A nomogram prediction model was developed using Cox proportional hazards regression with the training set, and was validated internally. Model performance was evaluated based on calibration, discrimination, and clinical utility. Results The model, incorporating seven predictors—SOFA score, serum creatinine, blood urea nitrogen, albumin levels, Charlson comorbidity index, mean arterial pressure at CRRT initiation, and phosphate levels 24 h after CRRT initiation—demonstrated robust performance. It achieved a C-index of 0.810 in the training set and 0.794 in the validation set. Conclusions We developed and validated a predictive model based on seven key clinical predictors, showing excellent performance in identifying high-risk patients for 90-day mortality in AKI patients undergoing CRRT. Graphical abstract

Background One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. Methods/design This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. Discussion This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. Trial registration ClinicalTrials.gov identifier NCT01682590 , registered on 10 September 2012.

Background There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT. Methods/design This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the ‘early’ strategy, RRT is initiated immediately. In the ‘delayed’ strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO 2  < 35 mmHg) or in a context of mixed acidosis with a PaCO 2  ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO 2  > 95% or FiO 2  > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all. Discussion The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT. Trial registration ClinicalTrials.gov NCT01932190 .

Background Acute kidney injury remains a common complication in critically ill patients and despite multiple trials and observational studies, the optimal timing for initiation of renal replacement therapy is still unclear. The early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (ELAIN) study is a randomized, single-center, prospective, two-arm, parallel group trial to reduce mortality in patients with severe acute kidney injury. We describe the study design and discuss aspects of the need for a trial in this patient cohort. Methods/design Our plan is to randomize critically ill patients with acute kidney injury to ‘early’ or ‘late’ initiation of renal replacement therapy according to stage 2 and 3 of the KDIGO classification using a specific trial protocol. We plan to guide data collection and analysis using pre-existing definitions and testing. The primary endpoint is overall survival in a 90-day follow-up period. Secondary endpoints include 28-day, 60-day, 90-day and 1-year all-cause mortality, recovery of renal function, ICU and hospital length-of-stay. The primary analysis will be an intention-to-treat analysis; secondary analyses include treated analyses. We will also specify rules for handling data and determining outcome. Discussion Several challenges for study design and execution can be seen in our trial, and it should generate results that will inform and influence the practice of renal replacement therapy in critically ill patients with acute kidney injury. Trial registration German Clinical Trials Register: DRKS00004367 ( www.germanctr.de ); 28 May 2013.

Background Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant. Methods/design The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of <2 mmol/L) and without any inotropic or vasopressor agent. Secondary outcomes include individual components of the primary outcome, days alive without renal replacement, days alive without mechanical ventilation in 30 days, and new acute kidney injury. The sample size enables detection of a 13.5-h difference in the primary outcome with a type 1 error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD 30) among the 30-day survivors. After 150 included patients the statistician masked for allocation group will recalculate the sample size potentially increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will review the safety data after 100 patients. Discussion The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality. Trial registration ClinicalTrials.gov: NCT02579525 . Registered on 19 October 2015.

Purpose Obesity is a public health challenge and a risk factor for chronic and acute kidney injury (AKI). The impact of kidney replacement therapy (KRT) on mortality in this specific population remains unclear. The objectives of this study were to evaluate the association between KRT and short- and long-term outcomes in patients with obesity, and to analyze trends over time in mortality as well as AKI and KRT incidence. Methods A retrospective analysis was conducted on all consecutive patients with obesity (body mass index ≥ 30 kg/m 2 ) admitted to a medico-surgical intensive care unit from 2009 to 2024. AKI was defined using KDIGO criteria. The primary outcome was 90-day mortality assessed with Kaplan–Meier curves and multivariate Cox analysis. Secondary outcomes included 1-year mortality and time trends assessed on 90-day mortality, AKI, and KRT incidence, as well as SAPS II score. Results Among 2,192 patients with obesity included in the study, 295 (13.5%) required KRT. The 90-day mortality was significantly higher in the KRT group compared to the non-KRT group (49.8% (95% CI [44.1–55.5] vs. 18.9% (95% CI [17.2–20.7]), p  < 0.0001). Multivariate analysis confirmed that KRT was independently associated with increased mortality. Over the 15-year period, AKI incidence decreased ( p  < 0.001). Conclusion Among critically ill obese patients, KRT was independently associated with increased 90-day mortality. These results highlight the need for prospective studies to better define optimal management strategies in this high-risk population.