Dataset Information

Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials.

ABSTRACT:

Background

Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.

Methods

We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation.

Results

We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, - 14%; 95% confidence interval, - 27% to - 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, - 5% to 21% in patients at intermediate-low risk).

Conclusions

We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.

SUBMITTER: Grolleau F

PROVIDER: S-EPMC8939225 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials.

Grolleau François F Porcher Raphaël R Barbar Saber S Hajage David D Bourredjem Abderrahmane A Quenot Jean-Pierre JP Dreyfuss Didier D Gaudry Stéphane S

Critical care (London, England) 20220321 1

<h4>Background</h4>Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.<h4>Methods</h4>We used data from the AKIK ...[more]

PMID: 35313942

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Project description:BackgroundIntermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI.MethodsThis is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting.ResultsA total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients.ConclusionCompared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.

Project description:BackgroundContinuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.ObjectiveWe aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.Derivation cohortPatients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).Validation cohortInternal validation occurred in a testing group of patients from the dataset (20%).Prediction modelRetrospective international multicenter study utilizing an 80/20 training and testing cohort split, and logistic regression with L2 regularization (LR), decision tree, random forest (RF), gradient boosting machine, and support vector machine with linear kernel to predict ICU and hospital survival. Model performance was determined by the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) due to the imbalance in the dataset.ResultsOf the 933 patients included in this study, 538 (54%) were male with a median age of 8.97 years and interquartile range (1.81-15.0 yr). The ICU mortality was 35% and hospital mortality was 37%. The RF had the best performance for predicting ICU mortality (AUROC, 0.791 and AUPRC, 0.878) and LR for hospital mortality (AUROC, 0.777 and AUPRC, 0.859). The top two predictors of ICU survival were Pediatric Logistic Organ Dysfunction-2 score at CRRT initiation and admission diagnosis of respiratory failure.ConclusionsThese are the first ML models to predict survival at ICU and hospital discharge in children and young adults receiving CRRT. RF outperformed other models for predicting ICU mortality. Future studies should expand the input variables, conduct a more sophisticated feature selection, and use deep learning algorithms to generate more precise models.

Project description:BackgroundAmong critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization.MethodsWe conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables.ResultsAmong 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (- 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08).ConclusionsEarlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality.Trial registrationClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722 , registered October 6, 2015.

Project description:BackgroundVascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury.Patients and methodsWe performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected.ResultsAmong the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34-4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98-1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64-1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred.ConclusionFemoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.

Project description:ObjectivesThrombocytopenia is common in critically ill patients treated with continuous renal replacement therapy and decreases in platelets following continuous renal replacement therapy initiation have been associated with increased mortality. Platelets play a role in innate and adaptive immunity, making it plausible that decreases in platelets following continuous renal replacement therapy initiation predispose patients to development of infection. Our objective was to determine if greater decreases in platelets following continuous renal replacement therapy correlate with increased rates of secondary infection.DesignRetrospectivecohort analysis.SettingThis study uses a continuous renal replacement therapy database from Mayo Clinic (Rochester, MN), a tertiary academic center.ParticipantsAdult patients who survived until ICU discharge and were on continuous renal replacement therapy for less than 30 days were included. A subgroup analysis was also performed in patients with thrombocytopenia (platelets < 100 × 103/µL) at continuous renal replacement therapy initiation.Measurements and main resultsThe primary predictor variable was a decrease in platelets from precontinuous renal replacement therapy levels of greater than 40% or less than or equal to 40%, although multiple cut points were analyzed. The primary outcome was infection after ICU discharge, and secondary endpoints included post-ICU septic shock and post-ICU mortality. Univariable, multivariable, and propensity-adjusted analyses were used to determine associations between the predictor variable and the outcomes.ResultsAmong 797 eligible patients, 253 had thrombocytopenia at continuous renal replacement therapy initiation. A greater than 40% decrease in platelets after continuous renal replacement therapy initiation was associated in the multivariable-adjusted models with increased odds of post-ICU infection in the full cohort (odds ratio, 1.49; CI, 1.02-2.16) and in the thrombocytopenia cohort (odds ratio, 2.63; CI, 1.35-5.15) cohorts.ConclusionsPlatelet count drop by greater than 40% following continuous renal replacement therapy initiation is associated with an increased risk of secondary infection, particularly in patients with thrombocytopenia at the time of continuous renal replacement therapy initiation. Further research is needed to evaluate the impact of both continuous renal replacement therapy and platelet loss on subsequent infection risk.

Project description:Estimating glomerular filtration (eGFR) after Continuous Renal Replacement Therapy (CRRT) is important to guide drug dosing and to assess the need to re-initiate CRRT. Standard eGFR equations cannot be applied as these patients neither have steady-state serum creatinine concentration nor average muscle mass. In this study we evaluate the combination of dynamic renal function with CT-scan based correction for aberrant muscle mass to estimate renal function immediately after CRRT cessation. We prospectively included 31 patients admitted to an academic intensive care unit (ICU) with a total of 37 CRRT cessations and measured serum creatinine before cessation (T1), directly (T2) and 5 h (T3) after cessation and the following two days when eGFR stabilized (T4, T5). We used the dynamic creatinine clearance calculation (D3C) equation to calculate eGFR (D3CGFR) and creatinine clearance (D3Ccreat) between T2-T3. D3Ccreat was corrected for aberrant muscle mass when a CT-scan was available using the CRAFT equation. We compared D3CGFR to stabilized CKD-EPI at T5 and D3CCreat to 4-h urinary creatinine clearance (4-h uCrCl) between T2-T3. We retrospectively validated these results in a larger retrospective cohort (NICE database; 1856 patients, 2064 cessations). The D3CGFR was comparable to observed stabilized CKD-EPI at T5 in the prospective cohort (MPE = - 1.6 ml/min/1.73 m2, p30 = 76%) and in the retrospective NICE-database (MPE = 3.2 ml/min/1.73 m2, p30 = 80%). In the prospective cohort, the D3CCreat had poor accuracy compared to 4-h uCrCl (MPE = 17 ml/min/1.73 m2, p30 = 24%). In a subset of patients (n = 13) where CT-scans were available, combination of CRAFT and D3CCreat improved bias and accuracy (MPE = 8 ml/min/1.73 m2, RMSE = 18 ml/min/1.73 m2) versus D3CCreat alone (MPE = 18 ml/min/1.73 m2, RMSE = 32 ml/min/1.73 m2). The D3CGFR improves assessment of eGFR in ICU patients immediately after CRRT cessation. Although the D3CCreat had poor association with underlying creatinine clearance, inclusion of CT derived biometric parameters in the dynamic renal function algorithm further improved the performance, stressing the role of muscle mass integration into renal function equations in critically ill patients.

Dataset Information

Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials.

Background

Methods

Results

Conclusions

Publications

Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials.

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