Kidney international
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Kidney international · Oct 2015
Randomized Controlled Trial Multicenter Study Comparative StudyComparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.
In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. ⋯ Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.
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Kidney international · Oct 2015
Comparative StudyHeterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes.
Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). As epigenetic processes control gene expression in a cell- and environment-defined manner, understanding the epigenetic pathways that regulate genes altered by AKI may open vital new insights into the complexities of disease pathogenesis and identify possible therapeutic targets. Here we used matrix chromatin immunoprecipitation and integrative analysis to study 20 key permissive and repressive epigenetic histone marks at transcriptionally induced Tnf, Ngal, Kim-1, and Icam-1 genes in mouse models of AKI; unilateral renal ischemia/reperfusion, lipopolysaccharide (LPS), and their synergistically injurious combination. ⋯ Epigenetic alterations at these genes exhibited distinct time-dependent changes that shared some similarities, such as reduction in repressive histone modifications, and also had major ischemia/reperfusion versus endotoxin differences. Thus, diversity of changes at AKI genes in response to different insults indicates involvement of several epigenetic pathways. This could be exploited pharmacologically through rational-drug design to alter the course and improve clinical outcomes of this syndrome.
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Kidney international · Oct 2015
CommentDoes early-start renal replacement therapy improve outcomes for patients with acute kidney injury?
There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI), and wide international practice variation. Wald et al. report a pilot randomized trial examining accelerated use of RRT for moderate AKI in the intensive care unit, providing a workable design for a definitive trial examining the timing of RRT in critical illness.