Timing of RRT initiation in critically-ill patients: time for precision medicine

Abstract

Recently published randomized controlled trials have brought a focus upon the timing of renal replacement therapy (RRT) initiation in critically-ill patients (1,2). The AKIKI study randomized 620 ICU patients with severe acute kidney injury (AKI) [kidney disease improving global outcomes (KDIGO) classification, stage 3] to either immediate initiation of RRT or delayed initiation according to predetermined mandatory RRT criteria (1). Gaudry et al. found no significant difference in mortality between early and delayed RRT initiation strategies in critically-ill patients results, suggesting that careful monitoring of patients for predetermined mandatory RRT criteria may safely allow delaying RRT in ventilated and/or catecholaminedependent patients with severe AKI. To a more detailed unadjusted subpopulation analyses however, it seems that results may have been influenced by differences in patient outcomes within the delayed-RRT group. Indeed, among patients in the delayed group, those without RRT had a significantly decreased risk of death [hazard ratio =0.71 (0.52;0.97); P=0.031] while those who received delayed RRT had significantly increased risk of death [hazard ratio =1.40 (1.08;1.8); P=0.011]. These results suggest that patients who will never have required RRT probably benefit from not being exposed to potential complications of RRT while patients who definitely required RRT suffer from delayed initiation. The authors mitigate these results by performing an adjustment to baseline severity, after which differences were no longer significant. Given the important implications of the unadjusted subpopulation analysis, adjustment to baseline severity may not have been sufficient to completely describe results and the related phenomena. Rather, studies show that even when adjusting for severity, fluid accumulation remains a major risk factor for death in ICU patients with AKI (3-6). Therefore, adjusting-to or stratifying-by fluid accumulation could have confirmed or accentuated the opposite behaviors observed within the delayed-RRT group. Although no data on fluid accumulation was provided aside from pulmonary edema incidence, increased diuretic use in the delayed-RRT group [4 patients (1.3%) vs. 112 patients (36.5%); P<0.001] shows that fluid accumulation was a major issue nonetheless.Fluid accumulation was among inclusion criteria in the recent ELAIN trial which randomized 231 critically-ill patients with AKI (KDIGO stage 2) to either early (within 8 hours of diagnosis of KDIGO stage 2 AKI; n=112) or delayed (within 12 hours of stage 3 AKI or no initiation; n=119) initiation of RRT (2). The use of biomarkers was also among inclusion criteria in the ELAIN trial: plasma neutrophil gelatinase-associated lipocalin (NGAL) >150 ng/mL. Zarbock et al. found increased survival in early versus delayed-RRT suggesting that "early" RRT-initiation earlier than the in the AKIKI trial (KDIGO stage 2 vs. stage 3) in patients with both fluid accumulation and NGAL-positive AKI is beneficial.Given possible risks to patient subpopul...

Critical Care Nephrology: A Multidisciplinary Approach

“…Nephrologists should make rounds in the ICU together with ICU physicians to avoid the development of emergency conditions that require urgent extracorporeal therapies [19,20] . The time of initiation of RRT can therefore be defined by every single patient need (as suggested by precision medicine) rather than being justified by conflicting randomized controlled trials [21,22] .…”

Guiding Physician Decisions for Initiating Dialysis for AKI: Is Progress on the Horizon?

“…Although the study involved only nine nephrologists, the authors did not provided data on the extent that physicians were consistent in their decisions and the point in the course of illness that the SCAMP were recommendations provided. The lack of agreement between physician and algorithm may reflect the need for assessing and incorporating more quantitative parameters in the decision-making algorithm (15). Again, this emphasizes that the clinical decision to initiate or withhold RRT should be on the basis of a dynamic monitoring of interaction of kidney function and the demand imposed by overall illness rather than any set of absolute conditions (1,(15)(16)(17)(18)(19).…”

“…The lack of agreement between physician and algorithm may reflect the need for assessing and incorporating more quantitative parameters in the decision-making algorithm (15). Again, this emphasizes that the clinical decision to initiate or withhold RRT should be on the basis of a dynamic monitoring of interaction of kidney function and the demand imposed by overall illness rather than any set of absolute conditions (1,(15)(16)(17)(18)(19). Ideally, renal support should start when a mismatch between kidney demand and capacity exists or is anticipated.…”