Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial).
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SUBMITTER: Lumlertgul N
PROVIDER: S-EPMC5909278 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial).
Lumlertgul Nuttha N Peerapornratana Sadudee S Trakarnvanich Thananda T Pongsittisak Wanjak W Surasit Kajbundit K Chuasuwan Anan A Tankee Pleumjit P Tiranathanagul Khajohn K Praditpornsilpa Kearkiat K Tungsanga Kriang K Eiam-Ong Somchai S Kellum John A JA Srisawat Nattachai N
Critical care (London, England) 20180419 1
<h4>Background</h4>The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine wh ...[more]
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Project description:BackgroundTiming of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework.MethodsWe performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero-one inflated beta regression.ResultsThe posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] - 3.30%; 3.40%], - 0.39% [95% CrI - 3.46%; 3.00%], and 0.64% [95% CrI - 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of - 3.55 days [95% CrI - 6.38; - 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI - 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66.ConclusionsIn a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.
| S-EPMC9404618 | 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:Background:The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) remains controversial. Objective:In critically ill patients with AKI, to determine whether the accelerated initiation of RRT reduces mortality compared to a strategy of standard RRT initiation whereby RRT is initiated if urgent complications of AKI arise or based on clinician judgment. Design:Pragmatic allocation-concealed open-label randomized controlled trial. Setting:Up to 170 centers in Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Ireland, Italy, Finland, New Zealand, Switzerland, the United Kingdom, and the United States. Patients:We will enroll at least 2,866 critically ill patients with AKI stages 2 or 3 (defined as doubling of serum creatinine from baseline or serum creatinine ?354 µmol/L with increase of ?27 µmol/L from baseline or urine output <6 mL/kg in preceding 12 hours). Patients will be excluded if 1 or more of the following is/are present: potassium >5.5 mmol/L; bicarbonate <15 mmol/L; concomitant intoxication necessitating RRT; philosophy of care precluding escalation to RRT; any RRT in preceding 2 months; kidney transplant within the past year; preexisting estimated glomerular filtration rate <20 mL/min/1.73 m2; AKI etiology attributable to obstruction, glomerulonephritis, vasculitis, microangiopathy, or acute interstitial nephritis; clinician opinion that urgent RRT is mandated; or clinician opinion that RRT must be deferred. Methods:Participants will be randomized to one of two strategies: accelerated RRT initiation, which entails the initiation of RRT within 12 hours of the patient fulfilling all eligibility criteria, or standard RRT initiation, whereby clinicians would be discouraged from initiating RRT unless a conventional trigger for RRT initiation arises or if AKI persists for ?72 hours. Measurements:The primary outcome is all-cause mortality at 90 days following randomization. Key secondary outcomes include RRT dependence, residual kidney function, health services use, and health-related quality of life, all assessed at 90 days after randomization. In jurisdictions where it is feasible, participants will be followed through day 365 using linked administrative data. Results:Through March 18, 2019, we have recruited 2623 (92% of target) participants. Limitations:Reliance on physician declaration of equipoise may create heterogeneity across the trial population; open-label design may introduce bias and uneven postrandomization cointerventions; variations in practice (eg, choice of RRT modality and RRT prescription) likely exist across sites. Conclusions:Once complete, the STARRT-AKI trial will provide the most robust evidence to date to guide clinical practice on the optimal timing of RRT initiation among critically ill patients with AKI. Trial registration:Clinicaltrials.gov NCT02568722.
| S-EPMC6558541 | biostudies-literature
Project description:BackgroundThe use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.ResultsWe identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74-0.87) and 0.88 (95% CI 0.82-0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96-7.50), the pooled negative LR was 0.26 (95% CI 0.19-0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00-51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72-0.91) and 0.77 (95% CI 0.64-0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06-4.86) and 0.25 (95% CI 0.14-0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74-32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1-2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51-13.33).ConclusionThe FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.
| S-EPMC7206785 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear.MethodsIn this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach.ResultsWe identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]: - 0.04, 95% confidence intervals [CI] - 0.16 to 0.07, p = 0.46) and free of dialysis (log OR: - 0.03, 95% CI - 0.14 to 0.09, p = 0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11.ConclusionsIn this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases. Trial registration CRD42020201466, Sep 07, 2020. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201466 .
| S-EPMC7784335 | biostudies-literature
Project description:ObjectivesAmong 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.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal 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).ConclusionsAmong 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.
| S-EPMC10878545 | biostudies-literature
Project description:IntroductionAbrupt declines in kidney function often occur in patients with advanced chronic kidney disease and may exacerbate the need to initiate dialysis treatment. It is unclear how frequently such events occur in patients transitioning to chronic dialysis therapy, and what outcomes they are associated with.MethodsWe examined a national cohort of 23,349 US veterans with incident end-stage renal disease (ESRD) and with available pre-ESRD estimated glomerular filtration rate (eGFR) to identify abrupt declines in kidney function, defined as an unexpected >50% decrease in eGFR at the time of chronic dialysis transition. Associations with all-cause mortality and with renal recovery were examined in Cox proportional hazard and competing risk regression models.ResultsA total of 4804 (21%) patients experienced an abrupt decline in kidney function at dialysis transition. Renal recovery occurred in 586 (12.2%) and 297 (1.6%) patients with and without an abrupt decline, respectively (adjusted subhazard ratio: 4.42; 95% confidence interval [CI]: 3.72-5.27; P < 0.001). In the first 6 months after dialysis transition 1178 patients (24.5%) with abrupt decline died (annualized mortality rate 574/1000 patient-years), compared with 2354 deaths (12.7%) in patients without abrupt decline (274 deaths/1000 patient-years). An abrupt decline was associated with 45% higher mortality after multivariable adjustments (hazard ratio: 1.45; 95% CI: 1.33-1.57).ConclusionAbrupt declines in kidney function are common in patients transitioning to chronic dialysis, and are associated with higher mortality. Patients with abrupt declines also experience a higher rate of renal recovery; hence, careful attention to residual kidney function is warranted in these patients.
| S-EPMC5976817 | biostudies-literature
Project description:Background and objectivesIncomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied.Design, setting, participants, & measurementsWe conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing.ResultsUsing the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis.ConclusionsThe furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters.
| S-EPMC5586565 | biostudies-literature
Project description:BackgroundIn sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice. Both the Furosemide Stress Test (FST) and measurements of the urinary biomarkers TIMP-2*IGFBP-7, if applied solely, do not provide sufficient guidance. We tested the hypothesis that a combination of two tests, i.e., an upstream FST combined with downstream measurements of urinary TIMP-2*IGFBP-7 concentrations improves the accuracy in predicting RRT necessity.MethodsIn this prospective, multicenter study 100 patients with sepsis (diagnosed < 48h), AKI stage ≥ 2, and an indication for negative fluid balance were included between 02/2020 and 12/2022. All patients received a standardized FST and urinary biomarkers TIMP-2*IGFBP-7 were serially measured immediately before and up to 12 h after the FST. The primary outcome was the RRT requirement within 7 days after inclusion.Results32% (n = 32/99) of SA-AKI patients eventually required RRT within 7 days. With the FST, urine TIMP-2*IGFBP-7 decreased within 2 h from 3.26 ng2/mL2/1000 (IQR: 1.38-5.53) to 2.36 ng2/mL2/1000 (IQR: 1.61-4.87) in RRT and 1.68 ng2/mL2/1000 (IQR: 0.56-2.94) to 0.27 ng2/mL2/1000 (IQR: 0.12-0.89) and non-RRT patients, respectively. While TIMP-2*IGFBP-7 concentrations remained low for up to 12 h in non-RRT patients, we noted a rebound in RRT patients after 6 h. TIMP-2*IGFBP-7 before FST (accuracy 0.66; 95%-CI 0.55-0.78) and the FST itself (accuracy 0.74; 95%-CI: 0.64-0.82) yielded moderate test accuracies in predicting RRT requirement. In contrast, a two-step approach, utilizing FST as an upstream screening tool followed by TIMP-2*IGFBP-7 quantification after 2 h improved predictive accuracy (0.83; 95%-CI 0.74-0.90, p = 0.03) compared to the FST alone, resulting in a positive predictive value of 0.86 (95%-CI 0.64-0.97), and a specificity of 0.96 (95%-CI 0.88-0.99).ConclusionsThe combined application of an upstream FST followed by urinary TIMP-2*IGFBP-7 measurements supports highly specific identification of SA-AKI patients requiring RRT. Upcoming interventional trials should elucidate if this high-risk SA-AKI subgroup, identified by our predictive enrichment approach, benefits from an early RRT initiation.
| S-EPMC11246358 | biostudies-literature
Project description:Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage, timing, and clinical outcomes of the FST proposed thus far have been significantly different, which further accentuates the need for standardization in the application of the test in order to facilitate the comparison of results between series. This review will summarize published research regarding the usefulness of the FST in different settings, providing the reader some insights about the possible implications of FST in clinical decision-making in patients with kidney disease and the challenges that research will have to address in the near future before widely applying the FST.
| S-EPMC7247682 | biostudies-literature