Dialysis is the cornerstone of the management of kidney failure for acute kidney injury (AKI) and chronic kidney disease (CKD). However, dialysis is associated with complications, adverse events, cost, and decreased quality of life, especially if started too soon. Therefore, selecting the ideal time to initiate dialysis is paramount. Early initiation versus delayed initiation of dialysis has been a point of constant debate in nephrology. Earlier initiation of kidney replacement therapy (KRT) may help with fluid and electrolyte balance, removal of uremic toxins, and the prevention of uremic complications, but it exposes people to dialysis-related adverse events and greater time spent on dialysis.
The timing is generally well established for patients with progressive CKD who may be dialyzed with the onset of uremic symptoms or with the presence of uremic complications. The landmark Initiating Dialysis Early and Late (IDEAL) trial (1) showed that planned, early initiation of dialysis in CKD stage 5 was not associated with an improvement in survival or clinical outcomes compared with a delayed initiation.
Several randomized controlled trials (RCTs) have been performed over the past decade to attempt to answer the question of when dialysis should be initiated for patients with AKI. The ELAIN trial (2) was published in 2016 and examined almost entirely surgical patients (n = 231) from a single center. The study found a significant reduction in 90-day mortality with an early strategy compared with a delayed strategy. The AKIKI trial (3) was published just 1 week later but was a multicenter study that included patients in medical intensive care units (ICUs) who were more critically ill. AKIKI found no significant difference between early- and late-start strategies. The important drawbacks of these studies were that ELAIN was a single-center study that included only surgical patients and had a small sample size, and the AKIKI trial included only patients with advanced AKI, and only 50% of the patients received dialysis. The IDEAL-ICU (4) and STARRT-AKI (5) trials tried to correct the drawbacks of previous studies but found no significant difference in both strategies. The AKIKI 2 trial (6) tried to compare a delayed strategy with a more delayed strategy (both >72 hours) and also did not find any difference between the two approaches. In most studies, the early strategy was associated with fewer chances of AKI-related complications, such as hyperkalemia or pulmonary edema, and the delayed strategy was associated with less dialysis requirement and a higher incidence of spontaneous recovery of AKI.
A meta-analysis by Xiao et al. (7) included 12 RCTs with 5423 participants. The study found that early or delayed dialysis had similar rates of all-cause mortality at day 28 (38.7% vs. 38.9%). Another meta-analysis of 11 trials (8) showed no statistically significant effects on ICU length of stay, hospital length of stay, recovery of kidney function, and KRT dependence.
To date, most RCTs have not favored early or late initiation of dialysis but have robustly shown that early initiation has no benefit over late initiation of dialysis. The comparisons among the RCTs are challenging, due to variable causes of AKI, use of different populations, and use of different definitions for “early” and “late” dialysis. In conclusion, there is no optimal timing for KRT, and whether early dialysis is superior to delayed dialysis is a matter of controversy.
Cooper BA, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med 2010; 363:609–619. doi: 10.1056/NEJMoa1000552
Zarbock A, et al. 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. JAMA 2016; 315:2190–2199. doi: 10.1001/jama.2016.5828
Gaudry S, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 2016; 375:122–133. doi: 10.1056/NEJMoa1603017
Barbar SD, et al. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med 2018; 379:1431–1442. doi: 10.1056/NEJMoa1803213
Bagshaw SM, et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med 2020; 383:240–251. doi: 10.1056/NEJMoa2000741
Gaudry S, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): A multicentre, open-label, randomised, controlled trial. Lancet 2021; 397:1293–1300. doi: 10.1016/S0140-6736(21)00350-0
Xiao C, et al. The efficacy and safety of early renal replacement therapy in critically ill patients with acute kidney injury: A meta-analysis with trial sequential analysis of randomized controlled trials. Front Med (Lausanne) 2022; 9:820624. doi: 10.3389/fmed.2022.820624
- Search Google Scholar
- Export Citation
, Xiao C The efficacy and safety of early renal replacement therapy in critically ill patients with acute kidney injury: A meta-analysis with trial sequential analysis of randomized controlled trials. Front Med (Lausanne) 2022; 9: 820624. doi: 10.3389/fmed.2022.820624
Xiao L, et al. Early versus late initiation of renal replacement therapy for acute kidney injury in critically ill patients: A systematic review and meta-analysis. PLoS One 2019; 14:e0223493. doi: 10.1371/journal.pone.0223493