Importance Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown. Objective To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality. Design, Setting, and Participants Single-center randomized clinical trial of 231 critically ill patients with AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (≥2 times baseline or urinary output Interventions Early (within 8 hours of diagnosis of KDIGO stage 2; n = 112) or delayed (within 12 hours of stage 3 AKI or no initiation; n = 119) initiation of RRT. Main Outcomes and Measures The primary end point was mortality at 90 days after randomization. Secondary end points included 28- and 60-day mortality, clinical evidence of organ dysfunction, recovery of renal function, requirement of RRT after day 90, duration of renal support, and intensive care unit (ICU) and hospital length of stay. Results Among 231 patients (mean age, 67 years; men, 146 [63.2%]), all patients in the early group (n = 112) and 108 of 119 patients (90.8%) in the delayed group received RRT. All patients completed follow-up at 90 days. Median time (Q1, Q3) from meeting full eligibility criteria to RRT initiation was significantly shorter in the early group (6.0 hours [Q1, Q3: 4.0, 7.0]) than in the delayed group (25.5 h [Q1, Q3: 18.8, 40.3]; difference, −21.0 [95% CI, −24.0 to −18.0]; P P  = .03). More patients in the early group recovered renal function by day 90 (60 of 112 patients [53.6%] in the early group vs 46 of 119 patients [38.7%] in the delayed group; odds ratio [OR], 0.55 [95% CI, 0.32 to 0. 93]; difference, 14.9% [95% CI, 2.2% to 27.6%]; P  = .02). Duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group (RRT: 9 days [Q1, Q3: 4, 44] in the early group vs 25 days [Q1, Q3: 7, >90] in the delayed group; P  = .04; HR, 0.69 [95% CI, 0.48 to 1.00]; difference, −18 days [95% CI, −41 to 4]; hospital stay: 51 days [Q1, Q3: 31, 74] in the early group vs 82 days [Q1, Q3: 67, >90] in the delayed group; P Conclusions and Relevance Among critically ill patients with AKI, early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days. Further multicenter trials of this intervention are warranted. Trial Registration German Clinical Trial Registry Identifier:DRKS00004367

https://jamanetwork.com/journals/jama/articlepdf/2522434/joi160051.pdf

Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial

BackgroundThe timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. MethodsIn this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1603017

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673613606479.pdf

Acute kidney injury: an increasing global concern

Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling evidence indicates that the incidence of AKI is rapidly increasing, particularly among hospitalized patients with acute illness and those undergoing major surgery. This increase might be partially attributable to greater recognition of AKI, improved ascertainment in administrative data and greater sensitivity of consensus diagnostic and classification schemes. Other causes could be an ageing population, increasing incidences of cardiovascular disease, diabetes mellitus and chronic kidney disease (CKD), and an expanding characterization of modifiable risk factors, such as sepsis, administration of contrast media and exposure to nephrotoxins. The sequelae of AKI are severe and characterized by increased risk of short-term and long-term mortality, incident CKD and accelerated progression to end-stage renal disease. AKI-associated mortality is decreasing, but remains unacceptably high. Moreover, the absolute number of patients dying as a result of AKI is increasing as the incidence of the disorder increases, and few proven effective preventative or therapeutic interventions exist. Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.

/pdf/acute-kidney-injury-epidemiology-outcomes-and-economics-3cepxv6zfs.pdf

Acute kidney injury—epidemiology, outcomes and economics

https://www.kidney-international.org/article/S0085-2538(19)30601-5/pdf

Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment.

Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July 2010. Eligible studies selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI. We identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There was significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patient population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however, significantly affect the odds of dialysis dependence beyond hospitalization (OR 0.62 0.34 to 1.13, I2 = 69.6%). Earlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.

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A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis

Simon S Mogensen

Papers

A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis