Dr Swapnil Pawar August 22, 2020 696 5

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Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury

The STARRT-AKI Investigators

 for the Canadian Critical Care Trials Group, the Australian and New Zealand Intensive Care Society Clinical Trials Group, the United Kingdom Critical Care Research Group, the Canadian Nephrology Trials Network, and the Irish Critical Care Trials Group*

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    STARRT-AKI Trial
    Dr Swapnil Pawar

Acute kidney injury occurs in up to 50% of critically ill patients and is associated with high morbidity and mortality. Renal replacement therapy (RRT) can rapidly correct life-threatening complications associated with acute kidney injuries, such as severe hyperkalemia, metabolic acidosis, or pulmonary edema due to fluid overload. However, the appropriate circumstances for initiating RRT when severe complications are not present remain controversial and uncertain. Early initiation of RRT can allow better control of metabolic abnormalities and other complications associated with increased mortality, but could needlessly expose patients to iatrogenic complications (hypotension, bleeding, infection, or hypothermia). The deliberate deferral of RRT initiation can allow time for spontaneous renal function recovery, thereby obviating the need for RRT.

Several trials on RRT initiation strategies have been published, the three largest of which (AKIKI, IDEAL-ICU, and ELAIN) yielded conflicting results. Although the ELAIN trial (2016) showed a better survival outcome with early RRT, AKIKI (2016) and IDEAL-ICU (2018) did not find a survival difference between early and delayed RRT initiation strategies.

Hypothesis – 

An accelerated strategy for renal-replacement therapy would result in a lower risk of death from any cause at 90 days than a  standard strategy.

Setting: Randomized controlled trial; 168 hospitals, 15 countries.

Inclusion Criteria:

Adults more than 18 years, admitted to the ICU

AKI ≥1.13 mg/dl in women, 1.47 mg/dl in men

and severe acute kidney injury that was categorized as stage 2 or 3 of the Kidney Disease

Intervention –      

Accelerated: Clinicians were to commence renal-replacement therapy as soon as possible and within 12 hours after patients had met full eligibility criteria.

Standard strategy:

  • Serum potassium level of 6.0 mmol or more
  • pH of 7.20
  • Serum bicarbonate level of 12 mmol per liter or less
  • Evidence of severe respiratory failure based on a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 or less
  • Clinical perception of volume overload
  • Persistent acute kidney injury for at least 72 hours after randomization

No compulsion to commence RRT; besides, clinicians could commence RRT whenever they considered based on their judgment.

Discontinuation of renal-replacement therapy occurred at the time of recovery of kidney function, withdrawal of life-sustaining support, or death.

Sample Size calculation:

on the basis of an assumed 90-day mortality of 40% in the standard strategy group; assuming a 15% relative between-group difference (absolute difference, 6 percentage points). 2866 patients would provide a power of 90%; two-sided significance level of 0.05.

Results – 

Accelerated group: dialysis at a median of 6.1 hours (interquartile range, 3.9 to 8.8) after in 1418 of 1465 (96.8%).

Standard-strategy group: in 903 of 1462 patients only (61.8%) at a median of 31.1 hours (interquartile range, 19.0 to 71.8)

Primary Outcome – 

Death from any cause at 90 days  – 43.9% in Accelerated strategy group Vs 43.7% in the standard strategy group. ( RR – 1.00, CI – 0.93-1.09)

Secondary outcomes  

No difference in 28-day, ICU mortality, and hospital mortality

Also, no difference in Health-related quality of life

Patients in the accelerated group had a shorter ICU stay than the standard group (9 days vs 10 days)

Re-hospitalization at 90-d was more in the accelerated strategy group

No difference in subgroup analysis

Adverse events:  23.0% vs.16.5%). Hypotension and hypo-phosphatemia were the most common adverse events with a significant between-group difference. There was no difference in serious adverse events between the two strategies.

Strengths – 

  1. Large multicentre international RCT
  2. Pragmatic design
  3. Good external and internal validity
  4. Adds significant information on epidemiological profile of AKI in ICU
  5. Evaluated meaningful secondary outcomes such as Frailty.


  1. A large number of exclusions
  2. The decision to perform RRT or not was finally left to the judgment of the clinician; this could have led to bias

Summary  – 

Accelerated renal replacement strategy does not alter the mortality, however increases the dialysis dependence in patients with AKI admitted to ICU. Thus, an accelerated renal replacement strategy is not indicated in these patients.


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