Timing of Kidney Support Therapy in Acute Kidney Injury: What Are We Waiting For?

Bouchard, Josée; Mehta, Ravindra L.

doi:10.1053/j.ajkd.2021.07.014

Cited by 26 publications

(14 citation statements)

References 46 publications

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“…45-48 In addition, the decision to initiate KRT should be individualized and should take into consideration the current demand and capacity. 49-51…”

Section: Discussionmentioning

confidence: 99%

Kidney Replacement Therapy in COVID-19-Related Acute Kidney Injury: the Importance of Timing

Almeida,

Oliveira,

Teixeira

et al. 2024

Preprint

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The objective of this study was to evaluate two different criteria for deciding when KRT should be initiated in patients with COVID-19-related AKI, as well as to determine the impact of the timing of KRT, as defined by each criterion, on in-hospital mortality among such patients. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for delayed KRT than for timely KRT, 84% higher in the univariate analysis (OR=1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR=2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT appears to be associated with lower in-hospital mortality.

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“…45-48 In addition, the decision to initiate KRT should be individualized and should take into consideration the current demand and capacity. 49-51…”

Section: Discussionmentioning

confidence: 99%

Kidney Replacement Therapy in COVID-19-Related Acute Kidney Injury: the Importance of Timing

Almeida,

Oliveira,

Teixeira

et al. 2024

Preprint

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“…However, within these RCTs, thresholds for absolute criteria to initiate RRT without further delay are either imposed as an exclusion criterion or incorporated in delayed treatment rules. Although these absolute indications can make sense from a theoretical point of view, guidance on absolute values of their cut-offs is lacking [ 1 , 10 , 11 ]. We therefore evaluated different cut-offs for frequently used absolute indications to initiate RRT [ 3 , 5 – 7 , 10 , 11 ]: pH, serum potassium, and persisting oligo-anuria.…”

Section: Discussionmentioning

confidence: 99%

“…Although these absolute indications can make sense from a theoretical point of view, guidance on absolute values of their cut-offs is lacking [ 1 , 10 , 11 ]. We therefore evaluated different cut-offs for frequently used absolute indications to initiate RRT [ 3 , 5 – 7 , 10 , 11 ]: pH, serum potassium, and persisting oligo-anuria.…”

Section: Discussionmentioning

confidence: 99%

“…Lack of clarity thus remains on when to best initiate RRT. This is partly because RCTs have so far only evaluated very specific treatment rules, so-called dynamic treatment regimes (DTRs), which require immediately starting RRT once specific absolute criteria (defined as refractory metabolic acidosis (low pH), hyperkalaemia, and/or intractable volume overload [ 10 ] are attained. However, current guidelines do not quote specific thresholds for these absolute criteria [ 10 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Timing of dialysis in acute kidney injury using routinely collected data and dynamic treatment regimes

et al. 2022

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Background and objectives Defining the optimal moment to start renal replacement therapy (RRT) in acute kidney injury (AKI) remains challenging. Multiple randomized controlled trials (RCTs) addressed this question whilst using absolute criteria such as pH or serum potassium. However, there is a need for identification of the most optimal cut-offs of these criteria. We conducted a causal analysis on routinely collected data (RCD) to compare the impact of different pre-specified dynamic treatment regimes (DTRs) for RRT initiation based on time-updated levels of potassium, pH, and urinary output on 30-day ICU mortality. Design, setting, participants, and measurements Patients in the ICU of Ghent University Hospital were included at the time they met KDIGO-AKI-stage ≥ 2. We applied inverse-probability-of-censoring-weighted Aalen–Johansen estimators to evaluate 30-day survival under 81 DTRs prescribing RRT initiation under different thresholds of potassium, pH, or persisting oliguria. Results Out of 13,403 eligible patients (60.8 ± 16.8 years, SOFA 7.0 ± 4.1), 5622 (63.4 ± 15.3 years, SOFA 8.2 ± 4.2) met KDIGO-AKI-stage ≥ 2. The DTR that delayed RRT until potassium ≥ 7 mmol/l, persisting oliguria for 24–36 h, and/or pH < 7.0 (non-oliguric) or < 7.2 (oliguric) despite maximal conservative treatment resulted in a reduced 30-day ICU mortality (from 12.7% [95% CI 11.9–13.6%] under current standard of care to 10.5% [95% CI 9.5–11.7%]; risk difference 2.2% [95% CI 1.3–3.8%]) with no increase in patients starting RRT (from 471 [95% CI 430–511] to 475 [95% CI 342–572]). The fivefold cross-validation benchmark for the optimal DTR resulted in 30-day ICU mortality of 10.7%. Conclusions Our causal analysis of RCD to compare RRT initiation at different thresholds of refractory low pH, high potassium, and persisting oliguria identified a DTR that resulted in a decrease in 30-day ICU mortality without increase in number of RRTs. Our results suggest that the current criteria to start RRT as implemented in most RCTs may be suboptimal. However, as our analysis is hypothesis generating, this optimal DTR should ideally be validated in a multicentric RCT.

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“…Meanwhile, due to the complexity of etiology, the treatment of AKI has had little progress recently. Monitoring fluid, electrolyte, and acid-base balance, early recognition of complications, and kidney replacement therapy are the limited methods we can carry out ( Bagshaw and Wald, 2017 ; Meraz-Muñoz et al, 2021 ; Bouchard and Mehta, 2022 ). The drugs targeting the pathophysiological process of kidney injury are finite and need further study.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

Zhang

Cai

et al. 2022

Front. Genet.

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Background: Acute kidney injury (AKI) is a common clinical syndrome with limited methods of treatment and diagnosis. Although several molecules associated with AKI have been discovered, molecular mechanisms underlying AKI still remain unclear. Weighted gene co-expression network analysis (WGCNA) is a novel method to uncover the relationship between co-expression genes and clinical traits at the system level.Methods: First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples.Results: Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models.Conclusion: The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a “high immune but low metabolic activity” expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.

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Timing of Kidney Support Therapy in Acute Kidney Injury: What Are We Waiting For?

Cited by 26 publications

References 46 publications

Kidney Replacement Therapy in COVID-19-Related Acute Kidney Injury: the Importance of Timing

Kidney Replacement Therapy in COVID-19-Related Acute Kidney Injury: the Importance of Timing

Timing of dialysis in acute kidney injury using routinely collected data and dynamic treatment regimes

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury

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