Purpose
We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.
Methods
This ...multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.
Results
Mean (SD) cumulative fluid balance at 72 h from randomization was − 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) − 1148 mL (− 2200 to − 96) mL,
P
= 0.033. Median IQR duration of AKI was 2 1–3 and 3 2–7 days, respectively (median difference − 1.0 − 3.0 to 0.0,
P
= 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16–0.91),
P
= 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.
Conclusions
In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.
Acute kidney injury in sepsis Bellomo, Rinaldo; Kellum, John A.; Ronco, Claudio ...
Intensive care medicine,
06/2017, Letnik:
43, Številka:
6
Journal Article
Recenzirano
Odprti dostop
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.
The narrative review aims to discuss recent results and important knowledge gaps regarding acute kidney injury (AKI) in postoperative patients undergone major noncardiac surgery.
Postoperative AKI ...affects approximately one-fifth of patients after major surgery, but the incidence varies according to the type of surgery. Preexisting chronic kidney disease is a major risk factor for postoperative AKI. It carries a substantial risk for postoperative adverse outcomes, as well as long-term mortality and morbidity. To prevent postoperative AKI, avoiding intraoperative hypotension and hypoperfusion as well as nephrotoxic substances are important. Currently, no efficient pharmacotherapy for prevention or treatment of AKI is available. In general, goal-directed management protocols have reduced the incidence of postoperative AKI. Additionally, a restrictive fluid management regimen might reduce organ edema and be beneficial also for the kidney function.
AKI is a frequent postoperative complication with a substantial risk for both short and long-term adverse events, and its incidence is likely to rise because of increasing major surgical procedures. Studies investigating better strategies to prevent and treat AKI in this population are urgently needed.
Acute kidney injury (AKI) is a frequently encountered syndrome especially among the critically ill. Current diagnosis of AKI is based on acute deterioration of kidney function, indicated by an ...increase in creatinine and/or reduced urine output. However, this syndromic definition encompasses a wide variety of distinct clinical features, varying pathophysiology, etiology and risk factors, and finally very different short- and long-term outcomes. Lumping all AKI together may conceal unique pathophysiologic processes specific to certain AKI populations, and discovering these AKI subphenotypes might help to develop targeted therapies tackling unique pathophysiological processes. In this review, we discuss the concept of AKI subphenotypes, current knowledge regarding both clinical and biomarker-driven subphenotypes, interplay with AKI subphenotypes and other ICU syndromes, and potential future and clinical implications.
The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a ...combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes.
We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5.
In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality.
In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.
Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial ...treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of studies difficult. The objective of this study was to assess how different approaches may impact estimates of AKI incidence and whether the association between AKI and 90-day mortality varied by the approach used.
Consecutive acutely admitted adult intensive care patients were included in a prospective observational study. AKI was determined following the KDIGO criteria during the first 7 days of ICU admission. In this post hoc analysis, we assessed whether AKI incidence differed when applying the KDIGO criteria in 30 different possible methods, varying in (A) serum creatinine (sCr), (B) urine output (UO), and (C) the method of combining these two into an outcome, e.g., severe AKI. We assessed point estimates and 95% confidence intervals for each incidence. Univariable regression was used to assess the associations between AKI and 90-day mortality.
A total of 1010 patients were included. Baseline creatinine was available in 449 (44%) patients. The incidence of any AKI ranged from 28% (95%CI 25-31%) to 75% (95%CI 72-77%) depending on the approach used. Methods to estimate missing baseline sCr caused a variation in AKI incidence up to 15%. Different methods of handling UO caused a variation of up to 35%. At 90 days, 263 patients (26%) had died, and all 30 variations were associated with 90-day mortality.
In this cohort of critically ill patients, AKI incidence varied from 28 to 75%, depending on the method used of applying the KDIGO criteria. A tighter adherence to KDIGO definitions is warranted to decrease the heterogeneity of AKI and increase the comparability of future studies.
Abstract
The incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, ...such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments. Our approach integrates a priori knowledge of the relationships between proteins and biological pathways and biological processes into sparse neural networks to create biologically informed neural networks. We employ these networks to differentiate between clinical subphenotypes of septic acute kidney injury and COVID-19, as well as acute respiratory distress syndrome of different aetiologies. To gain biological insight into the complex syndromes, we utilize feature attribution-methods to introspect the networks for the identification of proteins and pathways important for distinguishing between subtypes. The algorithms are implemented in a freely available open source Python-package (
https://github.com/InfectionMedicineProteomics/BINN
).
Purpose
We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs.
Methods
This prospective, observational, multi-centre study comprised adult ...emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients’ AKI status and risk factors for up to 5 days.
Results
We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5–41.1 %). The incidence was 17.2 % (15.8–18.6 %) for stage 1, 8.0 % (7.0–9.0 %) for stage 2 and 14.1 % (12.8–15.4 %) for stage 3 AKI. Of the 2,901 patients 296 10.2 % (9.1–11.3 %) received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717–774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0–28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9–36.5 %). All AKIN stages were independently associated with 90-day mortality.
Conclusions
The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.
Acute kidney injury is a heterogeneous syndrome and as such is associated with multiple predisposing conditions and causes all of which affect outcomes. Such heterogeneity may conceal the potential ...benefit of therapies when generally applied to patients with acute kidney injury (AKI). The discovery of pathophysiology-based subphenotypes could be of benefit in allocating current and future therapies to specific groups.
Clinical subphenotypes group patients into categories according to predisposing factors, disease severity, and trajectory. These may be helpful in assessing patient outcomes. Analyses of existing databases have revealed biological subphenotypes that are characterized by levels of biomarkers indicative of hyperinflammation and endothelial injury. Patients with increased levels of these biomarkers display higher mortality rates compared with those with lower levels and there is potential that this group might respond differently to therapies. However, challenges remain in the validation, generalizability, and application of these subphenotypes.
Subphenotyping may help reduce heterogeneity under the umbrella term of acute kidney injury. Despite challenges remain, the identification of AKI subphenotypes has opened the potential of AKI research focused on better targeted therapies.
No data on the development of conventional indications for RRT (refractory acidosis, hyperkalemia, uremia, oliguria/anuria, and volume overload) related to timing of RRT exist. The prevalence of ...conventional indications among critically ill patients on RRT for AKI was evaluated, and patients manifesting indications versus patients without indications were compared in terms of crude and adjusted 90-day mortality.
In this substudy of the Finnish Acute Kidney Injury study conducted in 2011 and 2012 in 17 intensive care units with 2901 patients, patients were classified as pre-emptive (no conventional indications) and classic (one or more indications) RRT recipients. Patients with classic RRT were divided into classic-urgent (RRT initiated ≤ 12 hours from manifesting indications) and classic-delayed (RRT >12 hours from first indication). Additionally, 2450 patients treated without RRT were matched to patients with pre-emptive RRT.
Of 239 patients treated with RRT, 134 (56.1%; 95% confidence interval 95% CI, 49.8% to 62.4%) fulfilled at least one conventional indication before commencing RRT. Crude 90-day mortality of 134 patients with classic RRT was 48.5% (95% CI, 40.0% to 57.0%), and it was 29.5% (95% CI, 20.8% to 38.2%) for the 105 patients with pre-emptive RRT. Classic RRT was associated with a higher risk for mortality (adjusted odds ratio, 2.05; 95% CI, 1.03 to 4.09). Forty-four patients with classic-delayed RRT showed higher crude mortality (68.2%; 95% CI, 54.4% to 82.0%) compared with patients with classic-urgent RRT, and this association persisted after adjustment for known confounders (odds ratio, 3.85; 95% CI, 1.48 to 10.22). Crude 90-day mortality of 67 1:1 matched patients with pre-emptive RRT was 26.9% (95% CI, 6.3% to 37.5%), and it was 49.3% (95% CI, 37.3% to 61.2%; P=0.01) for their non-RRT matches.
Patients on RRT after one or more conventional indications had both higher crude and adjusted 90-day mortality compared with patients without conventional indications. These findings require confirmation in an adequately powered, multicenter, randomized controlled trial.
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