Question 28

Critically evaluate early versus late initiation of Renal Replacement Therapy (RRT) in the critically ill patient.

[Click here to toggle visibility of the answers]

College answer

Not available.

Discussion

Rationale:

  • Renal failure results in the accumulation of uraemic toxins
  • The damage done by this accumulation is dose-dependent
  • There is no specific safe threshold value for the levels of these toxins
  • Ergo, the early removal of such toxins should be beneficial

Advantages of early RRT:

  • Specific benefits should theoretically include decreased fluid overload, earlier extubation, shorter ICU stay, lower risk of encephalopathy and improved mortality
  • Medical therapies for complications of renal failure are not benign, for instance causing deafness (frusemide), bowel obstruction (cation exchange resins) and increased CO2 (bicarbonate).
  • Delaying therapy is unlikely to have any immediate benefit as you have not treated anything.
  • For many patients presenting with renal failure, the need for future dialysis is apparent, and it would make no sense to delay this therapy until specific criteria are met (eg. to wait for "symptomatic" uraemia).

Disadvantages of early RRT:

  • Renal replacement therapy is not benign: there are well-documented complications.
  • Renal replacement therapy is not a "cure" for acute renal failure, it is merely a support strategy.
  • RRT may even cause a dalay in renal recovery
  • A proportion of patients with severe acute kidney injury never go on to require RRT
  • The safety of careful medical management is greater than the safety of careful RRT
  • Vascular access for CRRT is not without complications
  • Renal replacement therapy is not cheap (equipment, manpower and maintenance).
  • Most complications of acute renal failure are such that require relatively inexpensive and easily administered solutions, eg. calcium gluconate, soidum bicarbonate, frusemide, and so on.
  • The cost of RRT is not only in equipment but also in manpower and maintenance.

Evidence:

  • Early small-scale trials suggested a mortality risk reduction associated with early RRT, and this was also the finding of the ELAIN trial
  • Other trials (AKIKI, STARRT-AKI) have demonstrated no substantial difference in patient-centred outcomes between early and delayed initiation of RRT
  • In some of these (especially AKIKI), a substantial group of patients (~50%) in the delayed group never ended up receiving dialysis at all
  • For patients in whom RRT was delayed, AKIKI 2 investigators found that persistent oliguria (of over 72 hours) or a raised urea (over 40 mmol/L) were associated with poorer outcomes if the delay continued

Own practice:

  • "Any reasonable statement" should score marks here. 
  • One could say,
    • In my practice, I offer RRT only to patients with medically refractory acidaemia, electrolyte derangement or pulmonary oedema. In patients with oliguria and mild biochemical disturbances susceptible to medical therapy, I give renal function up to 72 hours to recover, or until urea has increased to over 40mmol/L, before I commence RRT.

References

Vaara, Suvi T., et al. "Timing of RRT based on the presence of conventional indications." Clinical Journal of the American Society of Nephrology 9.9 (2014): 1577-1585.

Wierstra, Benjamin T., et al. "The impact of “early” versus “late” initiation of renal replacement therapy in critical care patients with acute kidney injury: a systematic review and evidence synthesis." Critical Care 20.1 (2016): 1.

Gaudry, Stéphane, et al. "Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit." New England Journal of Medicine (2016).

Seabra, Victor F., et al. "Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis." American Journal of Kidney Diseases 52.2 (2008): 272-284.

Kleinknecht, Dieter, et al. "Uremic and non-uremic complications in acute renal failure: Evaluation of early and frequent dialysis on prognosis." Kidney international 1.3 (1972): 190-196.

Egal, Mohamud, et al. "Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis." Anesthesia & Analgesia 122.1 (2016): 173-185.

Ahmed, U. S., H. I. Iqbal, and S. R. Akbar. "Furosemide in Acute Kidney Injury–A Vexed Issue." Austin J Nephrol Hypertens 1.5 (2014): 1026.

Zarbock, Alexander, 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 315.20 (2016): 2190-2199.

STARRT-AKI Investigators. "Timing of initiation of renal-replacement therapy in acute kidney injury." New England Journal of Medicine (2020); 383:240-251

Gaudry, Stéphane, 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." The Lancet 397.10281 (2021): 1293-1300.