Hemodynamic instability related to renal replacement therapy (HIRRT) is a frequent complication of all renal replacement therapy (RRT) modalities commonly used in the intensive care unit. HIRRT is associated with increased mortality and may impair kidney recovery. Our current understanding of the physiologic basis for HIRRT comes primarily from studies of end-stage kidney disease patients on maintenance hemodialysis in whom HIRRT is referred to as 'intradialytic hypotension'. Nonetheless, there are many studies that provide additional insights into the underlying mechanisms for HIRRT specifically in critically ill patients. In particular, recent evidence challenges the notion that HIRRT is almost entirely related to excessive ultrafiltration. Although excessive ultrafiltration is a key mechanism, multiple other RRT-related mechanisms may precipitate HIRRT and this could have implications for how HIRRT should be managed (e.g., the appropriate response might not always be to reduce ultrafiltration, particularly in the context of significant fluid overload). This review briefly summarizes the incidence and adverse effects of HIRRT and reviews what is currently known regarding the mechanisms underpinning it. This includes consideration of the evidence that exists for various RRT-related interventions to prevent or limit HIRRT. An enhanced understanding of the mechanisms that underlie HIRRT, beyond just excessive ultrafiltration, may lead to more effective RRT-related interventions to mitigate its occurrence and consequences.

BackgroundHemodynamic instability related to renal replacement therapy (HIRRT) may increase the risk of death and limit renal recovery. Studies in end-stage renal disease populations on maintenance hemodialysis suggest that some renal replacement therapy (RRT)-related interventions (e.g., cool dialysate) may reduce the occurrence of HIRRT, but less is known about interventions to prevent HIRRT in critically ill patients receiving RRT for acute kidney injury (AKI). We sought to evaluate the effectiveness of RRT-related interventions for reducing HIRRT in such patients across RRT modalities.MethodsA systematic review of publications was undertaken using MEDLINE, MEDLINE in Process, EMBASE, and Cochrane’s Central Registry for Randomized Controlled Trials (RCTs). Studies that assessed any intervention’s effect on HIRRT (the primary outcome) in critically ill patients with AKI were included. HIRRT was variably defined according to each study’s definition. Two reviewers independently screened abstracts, identified articles for inclusion, extracted data, and evaluated study quality using validated assessment tools.ResultsFive RCTs and four observational studies were included (n = 9; 623 patients in total). Studies were small, and the quality was mostly low. Interventions included dialysate sodium modeling (n = 3), ultrafiltration profiling (n = 2), blood volume (n = 2) and temperature control (n = 3), duration of RRT (n = 1), and slow blood flow rate at initiation (n = 1). Some studies applied more than one strategy simultaneously (n = 5). Interventions shown to reduce HIRRT from three studies (two RCTs and one observational study) included higher dialysate sodium concentration, lower dialysate temperature, variable ultrafiltration rates, or a combination of strategies. Interventions not found to have an effect included blood volume and temperature control, extended duration of intermittent RRT, and slower blood flow rates during continuous RRT initiation. How HIRRT was defined and its frequency of occurrence varied widely across studies, including those involving the same RRT modality. Pooled analysis was not possible due to study heterogeneity.ConclusionsSmall clinical studies suggest that higher dialysate sodium, lower temperature, individualized ultrafiltration rates, or a combination of these strategies may reduce the risk of HIRRT. Overall, for all RRT modalities, there is a paucity of high-quality data regarding interventions to reduce the occurrence of HIRRT in critically ill patients.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-1965-5) contains supplementary material, which is available to authorized users.

BackgroundThe TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid‐associated single nucleotide polymorphisms (SNPs), identified by genome‐wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits.Methods and ResultsCharacterization of the risk locus reveals that it encompasses a gene, TRIB1‐associated locus (TRIBAL), composed of a well‐conserved promoter region and an alternatively spliced transcript. Bioinformatic analysis and resequencing identified a single SNP, rs2001844, within the promoter region that associates with increased plasma triglycerides and reduced high‐density lipoprotein cholesterol and coronary artery disease risk. Further, correction for triglycerides as a covariate indicated that the genome‐wide association studies association is largely dependent on triglycerides. In addition, we show that rs2001844 is an expression trait locus (eQTL) for TRIB1 expression in blood and alters TRIBAL promoter activity in a reporter assay model. The TRIBAL transcript has features typical of long noncoding RNAs, including poor sequence conservation. Modulation of TRIBAL expression had limited impact on either TRIB1 or lipid regulatory genes mRNA levels in human hepatocyte models. In contrast, TRIB1 knockdown markedly increased TRIBAL expression in HepG2 cells and primary human hepatocytes.ConclusionsThese studies demonstrate an interplay between a novel locus, TRIBAL, and TRIB1. TRIBAL is located in the genome‐wide association studies identified risk locus, responds to altered expression of TRIB1, harbors a risk SNP that is an eQTL for TRIB1 expression, and associates with plasma triglyceride concentrations.

micro-RNA-486-5p protects against kidney ischemic injury and modifies the apoptotic transcriptome in proximal tubules.