When to start a renal replacement therapy in acute kidney injury (AKI) patients: many irons in the fire.
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ABSTRACT:
SUBMITTER: Romagnoli S
PROVIDER: S-EPMC5066036 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acute kidney injury (AKI) is a common condition in critically ill patients, and may contribute to significant medical, social, and economic consequences, including death. Although there have been advances in medical technology, including continuous renal replacement therapy (CRRT), the mortality rate of AKI is high, and there is no fundamental treatment that can reverse disease progression. The decision to implement CRRT is often subjective and based primarily on the clinician's judgment without consistent and concrete guidelines or protocols regarding when to initiate and discontinue CRRT and how to manage complications. Recently, several randomized controlled trials addressing the initiation of renal replacement therapy in critically ill patients with AKI have been completed, but clinical application of the findings is limited by the heterogeneity of the objectives and research designs. In this review, the advantages and disadvantages of CRRT initiation, clinical guideline recommendations, and the results of currently published clinical trials and meta-analyses are summarized to guide patient care and identify future research priorities.
| S-EPMC8685358 | biostudies-literature
Project description:Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation.This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ?6.0 mmol/L; serum bicarbonate ?10 mmol/L; severe respiratory failure (PaO?/FiO?<200) or persisting acute kidney injury for ?72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events).The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.NCT01557361.
| S-EPMC3851593 | biostudies-literature
Project description:Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.
| S-EPMC4386097 | biostudies-literature
Project description:BackgroundThe EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.MethodsThis was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1?, IL-1?, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-?, tumour necrosis factor (TNF)-?, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.ResultsTwelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p?<?0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-?, IL-1?, IL-1?, and EGF, to 19.0 ml/min for TNF-?. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period.ConclusionEMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.Trial registrationNCT03231748, registered on 27th July 2017.
| S-EPMC7845048 | biostudies-literature
Project description:Recent data indicate AKI is very common among hospitalized Chinese patients and continuous renal replacement therapy (CRRT) is increasingly offered for treatment. However, only anecdotal information regarding CRRT's use in relation to other modalities and the specific manner in which it is prescribed exists currently. This report summarizes the results of a comprehensive physician survey designed to characterize contemporary dialytic management of AKI patients in China, especially with respect to the utilization of CRRT. The survey queried both nephrologists and critical care physicians across a wide spectrum of hospitals about factors influencing initial RRT modality selection, especially patient clinical characteristics and willingness to receive RRT, treatment location, and institutional capabilities. For patients initially treated with CRRT, data related to indication, timing of treatment initiation, dose, anticoagulation technique, and duration of therapy were also collected. Among AKI patients considered RRT candidates, the survey indicated 15.1% (95% CI, 12.3%-17.9%) did not actually receive dialysis at Chinese hospitals. The finding was largely attributed to prohibitively high therapy costs in the view of patients or their families. The survey confirmed the dichotomy in RRT delivery in China, occurring both in the nephrology department (with nephrologists responsible) and the intensive care unit (with critical care physicians responsible). For all patients who were offered and received RRT, the survey participants reported 63.9% (56.4%-71.3%) were treated initially with CRRT and 24.8% (19.2%-30.3%) with intermittent hemodialysis (HD) (P<0.001). The mean percentage of patients considered hemodynamically unstable at RRT initiation was 36.2% (31.3%-41.1%), although this figure was two-fold higher in patients treated initially with CRRT (43.1%; 35.8%-50.4%) in comparison to those initially treated with HD (22.4%; 16.4%-28.4%)(P<0.001). An overwhelming majority of intensive care patients were treated initially with CRRT (86.6%; 79.8-93.4%) while it was the initial modality in only 44.6% (33.5-55.7%) of patients treated in a nephrology department (P<0.001). Approximately 70% of respondents overall reported prescribing a CRRT dose in the range of 20-30 mL/kg/hr while approximately 20% of prescriptions fell above this range. Daily prescribed therapy duration demonstrated a marked divergence from values reported in the literature and standard clinical practice. Overall, the most common average prescribed value (50% of respondents) fell in the 10-20 hr range, with only 18% in the 20-24 hr range. Moreover, 32% of respondents reported an average prescribed value of less than 10 hrs per day. While the percentages for the 10-20 hrs range were essentially the same for nephrology and ICU programs, a daily duration of less than 10 hrs was much more common in nephrology programs (48.0%; 38.3%-57.9%) versus ICU programs (16%; 10.0%-24.6%)(P<0.001). Our analysis demonstrates both similarities and differences between RRT practices for AKI in China and those in the developed world. While some differences are driven by non-medical factors, future studies should explore these issues further as Chinese RRT practices are harmonized with those in the rest of the world.
| S-EPMC5503167 | biostudies-literature
Project description:BACKGROUND:Electronic health records (EHR) detect the onset of acute kidney injury (AKI) in hospitalized patients, and may identify those at highest risk of mortality and renal replacement therapy (RRT), for earlier targeted intervention. METHODS:Prospective observational study to derive prediction models for hospital mortality and RRT, in inpatients aged ?18?years with AKI detected by EHR over 1 year in a tertiary institution, fulfilling modified KDIGO criterion based on serial serum creatinine (sCr) measures. RESULTS:We studied 3333 patients with AKI, of 77,873 unique patient admissions, giving an AKI incidence of 4%. KDIGO AKI stages at detection were 1(74%), 2(15%), 3(10%); corresponding peak AKI staging in hospital were 61, 20, 19%. 392 patients (12%) died, and 174 (5%) received RRT. Multivariate logistic regression identified AKI onset in ICU, haematological malignancy, higher delta sCr (sCr rise from AKI detection till peak), higher serum potassium and baseline eGFR, as independent predictors of both mortality and RRT. Additionally, older age, higher serum urea, pneumonia and intraabdominal infections, acute cardiac diseases, solid organ malignancy, cerebrovascular disease, current need for RRT and admission under a medical specialty predicted mortality. The AUROC for RRT prediction was 0.94, averaging 0.93 after 10-fold cross-validation. Corresponding AUROC for mortality prediction was 0.9 and 0.9 after validation. Decision tree analysis for RRT prediction achieved a balanced accuracy of 70.4%, and identified delta-sCr???148??mol/L as the key factor that predicted RRT. CONCLUSION:Case fatality was high with significant renal deterioration following hospital-wide AKI. EHR clinical model was highly accurate for both RRT prediction and for mortality; allowing excellent risk-stratification with potential for real-time deployment.
| S-EPMC6357378 | biostudies-literature
Project description:Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI.
| S-EPMC5753434 | biostudies-literature
Project description:Sepsis-associated acute kidney injury (SA-AKI) is a major issue in medical, surgical and intensive care settings and is an independent risk factor for increased mortality, as well as hospital length of stay and cost. SA-AKI encompasses a proper pathophysiology where renal and systemic inflammation play an essential role, surpassing the classic concept of acute tubular necrosis. No specific treatment has been defined yet, and renal replacement therapy (RRT) remains the cornerstone supportive therapy for the most severe cases. The timing to start RRT, however, remains controversial, with early and late strategies providing conflicting results. This article provides a comprehensive review on the available evidence on the timing to start RRT in patients with SA-AKI.
| S-EPMC7290350 | biostudies-literature
Project description:IntroductionMalnutrition is common in patients with acute kidney injury (AKI), particularly in those requiring renal replacement therapy (RRT). Use of RRT removes metabolic waste products and toxins, but it will inevitably also remove useful molecules such as micronutrients, which might aggravate malnutrition. The RRT modalities vary in mechanism of solute removal; for example, intermittent hemodialysis (IHD) uses diffusion, continuous veno-venous hemofiltration (CVVH) uses convection, and sustained low-efficiency diafiltration (SLEDf) uses a combination of these.MethodsWe assessed micronutrient and amino acid losses in 3 different RRT modalities in patients with AKI (IHD, n = 27; SLEDf, n = 12; CVVH, n = 21) after correction for dialysis dose and plasma concentrations.ResultsTotal losses were affected by modality; generally CVVH >> SLEDf > IHD (e.g., amino acid loss was 18.69 ± 3.04, 8.21 ± 4.07, and 5.13 ± 3.1 g, respectively; P < 0.001). Loss of specific trace elements (e.g., copper and zinc) during RRT was marked, with considerable heterogeneity between RRT types (e.g., +849 and +2325 ?g/l lost during SLEDf vs. IHD, respectively), whereas effluent losses of copper and zinc decreased during CVVH (effect size relative to IHD, -3167 and -1442 ?g/l, respectively). B vitamins were undetectable in effluent, but experimental modeling estimated 40% to 60% loss within the first 15 minutes of RRT.ConclusionMicronutrient and amino acid losses are marked during RRT in patients with AKI, with variation between RRT modalities and micronutrients.
| S-EPMC6698297 | biostudies-literature
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress