• 1.

    Gaudry S, et al.. Initiation strategies for renal-replacement therapy in the intensive care unit. New Engl J Med 2016; 375:122133.

  • 2.

    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. J Am Med Assoc 2016; 315: 21902199.

    • Crossref
    • Search Google Scholar
    • Export Citation

When is Best to Initiate Dialysis in Critically Ill Patients with AKI?

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One of the more challenging decisions in nephrology is if and when to initiate dialysis and the timing of that initiation for patients with acute kidney injury (AKI). Because the initiation of renal replacement therapy (RRT) is a crucial decision for patients with life-threatening changes in fluids, electrolytes, and acid–base balance, expect this to remain a topic of discussion and debate in 2018.

Ashita Tolwani, MD, MSc, laid out the advantages and drawbacks when considering early initiation of dialysis in patients with AKI in her talk “Timing of AKI Dialysis: Why the Answer Is Not That Simple” at Kidney Week 2017. Among the advantages of initiating RRT are improved fluid management, prevention of fluid overload, and unloading or resting stressed and damaged kidneys. Drawbacks include risk of hypotension, decreased renal recovery, and infections from catheters.

Tolwani noted the limitations of observational studies for RRT timing:

  • ■ Lack of uniform definition of “early” vs. “late.”

  • ■ Better outcomes observed for the early group may be a result of a patient’s good prognosis from the outset.

  • ■ Patients who received RRT too early might have recovered from AKI without its having ever become necessary.

  • ■ The studies do not account for the outcomes of patients who never received RRT.

A review of prospective controlled trials did not illuminate as clear a distinction as one might expect. Take for example two completed studies: “Artificial Kidney Initiation in Kidney Injury (AKIKI) Trial” [multicenter, France] (1) and “Early vs. Late Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial” [single center, Germany] (2). Although the studies found different outcomes regarding the value of early vs. delayed initiation, they had significantly different base criteria. In AKIKI, which showed virtually no outcome differences between the early and delayed initiation, the following patient criteria were necessary:

  • ■ Adult, admission to an ICU + AKI compatible with acute tubular necrosis.

  • ■ Must be receiving invasive mechanical ventilation or catecholamine infusion.

  • ■ At least one of the following: serum creatinine >4.0 mg/dL or >3x baseline Cr, anuria for >12 h, oliguria (UO <0.3 mL/kg/h or <500 mL/day) for >24 h (KDIGO Stage 3).

In the ELAIN Trial, which demonstrated a significant difference in overall mortality probability, the criteria were significantly different:

  • ■ KDIGO stage 2 (serum creatinine 2x baseline Cr and/or urinary output <0.5 mL/kg/h ≥12 h) despite optimal resuscitation.

  • ■ Plasma NGAL >150 ng/mL.

  • ■ One of the following: a) severe sepsis; b) use of catecholamines; c) refractory fluid overload (worsening pulmonary edema, PaO2/FiO2 <300 mm Hg and/or fluid balance >10% of body weight); and d) development or progression of nonrenal organ dysfunction (SOFA [sequential organ failure assessment] score ≥2).

  • ■ Intention to provide full intensive care treatment for at least 3 days.

The trials also differed greatly in the patient cohorts studied. In AKIKI, 20% of participants were surgical patients, and in ELAIN, 93% of participants were surgical patients.

Looking for future guidance, Tolwani previewed the “Ongoing RRT Initiation RCT: STARRT-AKI (Canada) – Enrolling” which aims to enroll 2800 patients and “Ongoing RRT Initiation RCT: IDEAL-ICU study (France) – Initiated 2012” that has just completed.

With clinically based decisions of this nature involving so many factors, these studies are challenged to capture such important information as the inciting event that led to AKI, the degree of fluid overload, pre-existing comorbidities, and disease trajectory. Better trial design may inform better decision-making regarding the AKI-to-dialysis decision and the decision to terminate dialysis. Stay tuned as future trials unfold.

References

  • 1.

    Gaudry S, et al.. Initiation strategies for renal-replacement therapy in the intensive care unit. New Engl J Med 2016; 375:122133.

  • 2.

    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. J Am Med Assoc 2016; 315: 21902199.

    • Crossref
    • Search Google Scholar
    • Export Citation
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