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Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with incremental risk for death and chronic kidney disease and represents a mounting clinical challenge for healthcare professionals. Renal replacement therapy (RRT) use in ICU settings is rising, likely in response to similar trends in AKI, taken together with an ageing population burdened by high prevalence of multi-morbidity and high illness acuity. Numerous features of RRT prescription and delivery are not standardized, nor are they supported from high-quality evidence derived from randomized trials. Despite the publication of rigorous clinical practice guidelines focused on RRT for AKI that are intended to optimize the quality and reliability of RRT in ICU settings, practice patterns and outcomes continue to show significant variability. In this concise review, we aim to summarize new knowledge and recent advances for the provision of RRT for critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

Objectives: Renal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively invasive and resource intensive technology, there remains wide practice variation in its application. This systematic review appraised the evidence for quality indicators (QIs) of CRRT care in critically ill patients.Design: A comprehensive search strategy was developed and performed in five citation databases (Medline, Embase, CINAHL, Cochrane Library, and PubMed) and select grey literature sources. Two reviewers independently screened, selected, and extracted data using standardized forms. Each retrieved citation was appraised for quality using the Newcastle-Ottawa Scale (NOS) and Cochrane risk of bias tool. Data were summarized narratively.Measurements and Main Results: Our search yielded 8374 citations, of which 133 fulfilled eligibility. This included 97 cohort studies, 24 randomized controlled trials, 10 case-control studies, and 2 retrospective medical audits. The quality of retrieved studies was generally good. In total, 18 QIs were identified that were mentioned in 238 instances. Identified QIs were classified as related to structure (n = 4, 22.2 %), care processes (n = 9, 50.0 %), and outcomes (n = 5, 27.8 %). The most commonly mentioned QIs focused on filter lifespan (n = 98), small solute clearance (n = 46), bleeding (n = 30), delivered dose (n = 19), and treatment interruption (n = 5). Across studies, the definitions used for QIs evaluating similar constructs varied considerably. When identified, QIs were most commonly described as important (n = 144, 48.3 %), scientifically acceptable (n = 32, 10.7 %), and useable and/or feasible (n = 17, 5.7 %) by their primary study authors.Conclusions: We identified numerous potential QIs of CRRT care, characterized by heterogeneous definitions, varying quality of derivation, and limited evaluation. Further study is needed to prioritize a concise inventory of QIs to measure, improve, and benchmark CRRT care for critically ill patients.Systematic Review Registration: PROSPERO CRD42015015530. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristics and outcomes of critically ill patients with severe acute kidney injury (AKI) treated and not treated with renal replacement therapy (RRT). Methods: Secondary analysis of a multi-centre cohort study. Primary exposure was RRT. Primary outcome was propensity and multi-variable adjusted-hospital mortality. Results: We studied 1250 patients (71.3%) who received and 502 (28.7%) who did not receive RRT. Reasons for not starting RRT (not mutually exclusive) were limitations of support (33.6%, n=169), adequate urine output (46.2%; n=232), plan to observe (56.4%; n=283), and advanced age (12.6%; n=63). Mortality was higher in those not receiving RRT due to limitations and advanced age but lower for adequate urine output and plan to observe. Propensity and multi-variable adjusted analysis showed no statistical difference in hospital mortality (adj-OR 1.47; 95% CI, 0.93-2.24) in patients receiving RRT. Results were similar in a sensitivity analysis restricted to patients fulfilling risk, injury, failure, loss, end-stage kidney disease-FAILURE criteria (37.0%; n= 446) (adj-OR 1.36; 95% CI, 0.70-2.66). Conclusion: In this cohort, reasons for not starting RRT included limitations of support and perception of impending renal recovery. Despite similar risk of mortality after adjusting for selection bias and confounders, RRT-treated patients were fundamentally different from non-treated patients across a spectrum of variables that precludes valid comparison in observational data. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Our objective was to describe the current practice for initiation of RRT in this population. There is uncertainty regarding the optimal time to initiate renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI). Methods: Prospective study of patients receiving RRT in 6 intensive care units (ICUs) at 3 hospitals from July 2007 to August 2008. We characterized factors associated with start of RRT and evaluated their relationship with mortality. Results: We included 234 patients. RRT was initiated 1 day (0-4) after ICU admission (median [interquartile range]). Median creatinine was 331 μmol/L (225-446 μmol/L), urea 22.9 mmol/L (13.9-32.9 mmol/L), and RIFLE-Failure in 76.9%. Of traditional indications, Pao 2/Fio 2 < 200 (54.5%) and oliguria (32.9%) were most common. ICU and hospital mortality were 45.3% and 51.9%, respectively. In adjusted analysis, mortality at RRT initiation was associated with creatinine <332 μmol/L (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.5-5.4), change in urea from admission >8.9 mmol/L (OR 1.8; 95% CI, 1.0-3.4), urine output <82 mL/24 hours (OR 3.0; 95% CI, 1.4-6.5), fluid balance >3.0 L/24 hours (OR 2.3; 95% CI, 1.2-4.5), percentage of fluid overload >5% (OR 2.3; 95% CI, 1.2-4.7), 3 or more failing organs (OR 4.5; 95% CI, 1.2-4.2), Sequential Organ Failure Assessment score >14 (OR 2.3; 95% CI, 1.3-4.3), and start 4 days or more after admission (OR 4.3; 95% CI, 1.9-9.5). Mortality was higher as factors accumulated. Conclusion: In ICU patients requiring RRT, there was marked variation in factors that influence start of RRT. RRT initiation with fewer clinical triggers was associated with lower mortality. Timing of RRT may modify survival but requires appraisal in a randomized trial. [Copyright &y& Elsevier]

Background: The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury.Methods: We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality.Results: A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output.Conclusions: Acute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children and young adults. (Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Children's Hospital Medical Center and others; AWARE ClinicalTrials.gov number, NCT01987921 .). [ABSTRACT FROM AUTHOR]

Objectives: The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes.Design: We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy.Setting: Multiple centers involved in eight trials.Patients: Total of 4,588 trial participants.Intervention: Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality.Measurements and Main Results: Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94-1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, -2.14 d; [95% CI, -4.13 to -0.14]) and ICU length of stay (mean difference, -1.18 d; [95% CI, -1.95 to -0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58-0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29-0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66-1.40]).Conclusions: Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

Objective: Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Design: Retrospective cohort study. Setting: Linked population-wide administrative databases in Ontario, Canada. Patients: Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Interventions: Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Measurements and Main Results: Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% Cl, 0.65-0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Conclusions: Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis. [ABSTRACT FROM AUTHOR]