When should renal replacement therapy (RRT) be initiated in critically ill patients with acute kidney injury (AKI)?

Timing of Renal Replacement Therapy Initiation in Critically Ill Patients with AKI

Primary Recommendation

Initiate RRT immediately only when life-threatening complications exist (severe hyperkalemia with ECG changes, acute pulmonary edema unresponsive to diuretics, severe metabolic acidosis, or uremic complications); otherwise, adopt a delayed/standard initiation strategy based on clinical monitoring rather than early/preemptive initiation, as early RRT provides no mortality benefit and significantly increases adverse events including hypotension and infections. 1, 2, 3

Evidence from Major Trials (AKIKI, AKIKI-2, IDEAL-ICU, RENAL)

The collective evidence from multiple randomized controlled trials involving over 5,000 critically ill patients demonstrates that:

• Early RRT initiation (median 2-7.6 hours after meeting criteria) versus delayed initiation (median 21-57 hours) shows no difference in 28-day mortality (RR 1.01; 95% CI 0.94-1.09). 2

• Trial sequential analysis confirms this finding is conclusive, with the cumulative evidence crossing the futility boundary and reaching the required information size of 2,949 patients. 2

• Early RRT is associated with a 42% increased risk of hypotension (RR 1.42; 95% CI 1.23-1.63) and 34% increased risk of RRT-associated infections (RR 1.34; 95% CI 1.01-1.78). 2

• Early initiation leads to unnecessary RRT exposure in patients whose kidney function would have recovered spontaneously, resulting in wasted healthcare resources and preventable complications. 2, 3

Absolute Indications for Emergent RRT Initiation

Initiate RRT immediately when any of the following exist:

• Severe hyperkalemia with ECG changes (peaked T waves, widened QRS, loss of P waves) 4, 1, 5
• Acute pulmonary edema unresponsive to diuretic therapy 4, 1, 5
• Severe metabolic acidosis with impaired respiratory compensation 4, 1, 5
• Uremic complications: encephalopathy, pericarditis, or uremic bleeding 4, 1, 5
• Severe fluid overload causing respiratory compromise despite medical management 1, 5

Delayed/Standard Initiation Strategy

For patients reaching KDIGO Stage 2 or 3 AKI without emergent indications, monitor closely and consider the broader clinical context rather than single BUN or creatinine thresholds alone. 4, 1

Key monitoring parameters include:

• Trends in oliguria (urine output <0.5 mL/kg/h for >12 hours) rather than absolute values 6
• Progressive fluid overload despite diuretic therapy 6
• Worsening multi-organ dysfunction 6
• Rising potassium levels approaching dangerous thresholds (>6.0-6.5 mEq/L) 6
• Metabolic acidosis trending toward severe (pH <7.15) 6

The decision should be based on the dynamic relationship between metabolic/fluid demands and the kidney's capacity to meet them, requiring regular reassessment rather than a single time point. 4

Modality Selection Based on Hemodynamic Status

For hemodynamically unstable patients requiring vasopressor support, use continuous RRT (CRRT) rather than intermittent hemodialysis. 4, 1, 5

• CRRT is more physiologically appropriate in unstable patients, though RCTs have not demonstrated better mortality outcomes compared to intermittent RRT. 4

• For hemodynamically stable patients requiring rapid correction of severe hyperkalemia, intermittent hemodialysis is preferred due to faster potassium clearance. 5, 7

For patients with acute brain injury or increased intracranial pressure, CRRT carries lower risk of intracranial pressure changes compared to intermittent RRT. 4, 5

CRRT Dosing and Technical Specifications

When CRRT is selected:

• Deliver an effluent volume of 20-25 mL/kg/h for all CRRT modalities. 4, 1, 5
• Use bicarbonate-based replacement fluids rather than lactate-based solutions, especially in patients with shock, liver failure, or lactic acidemia. 5
• For anticoagulation, use regional citrate anticoagulation in patients without contraindications (severe liver failure, shock with lactic acidosis). 4

Intermittent RRT Dosing

When intermittent or extended RRT is used:

• Deliver a Kt/V of at least 1.2 per treatment, three times per week (total Kt/V of 3.9 per week). 4, 7

Vascular Access

• Use an uncuffed non-tunneled dialysis catheter of appropriate length and gauge for acute RRT initiation. 4
• First choice for site is the right internal jugular vein or femoral vein (femoral is inferior in patients with increased body mass). 4
• Consider cuffed catheter only in patients with expected prolonged RRT indication. 4

RRT Discontinuation Criteria

Discontinue RRT when kidney function has recovered sufficiently to meet patient needs or when RRT is no longer consistent with goals of care. 4, 1

• Urine output is the most robust predictor of successful discontinuation (sensitivity 66.2%, specificity 73.6%). 1
• Kidney recovery is defined as sustained independence from RRT for a minimum of 14 days. 5, 7
• Do not use diuretics to enhance kidney function recovery or reduce the duration or frequency of RRT. 4

Transition from CRRT to Intermittent Modalities

Consider transitioning from CRRT to intermittent hemodialysis when: 4, 1, 5

• Vasopressor support has been discontinued
• Hemodynamic stability has been achieved
• Intracranial hypertension has resolved (if present)
• Positive fluid balance can be adequately controlled by intermittent hemodialysis

Common Pitfalls to Avoid

• Do not initiate RRT based solely on elevated BUN (>80-100 mg/dL) or creatinine thresholds without considering clinical context and trends. 4, 1

• Do not use biomarkers alone to decide RRT initiation timing, as existing evidence does not support this approach. 4

• Avoid excessive ultrafiltration rates that cause hypotension, as this may delay renal recovery and cause re-injury to the kidney. 4, 5

• Do not continue RRT unnecessarily in patients whose kidney function is recovering, as this increases infection risk and healthcare costs without benefit. 2, 3

Special Population: Cirrhosis with AKI

In patients with cirrhosis and AKI (including hepatorenal syndrome), RRT indications are the same as in the general population. 4

• Early RRT may improve survival in acute liver failure, but data in cirrhosis suggest that RRT should not be limited to transplant candidates alone; decisions should be based on individual severity of illness with repeated risk stratification. 4

• CRRT is better tolerated than intermittent hemodialysis in cirrhotic patients, providing greater cardiovascular stability and allowing slower correction of severe hyponatremia. 4