Acute Kidney Injury in Critically Ill Patients

Background

• Acute kidney injury (AKI) is a heterogeneous syndrome defined by an abrupt decrease in kidney function based on increased serum creatinine and/or decreased urine output, and has been reported to affect 30%-60% of patients with a critical illness.
• Characteristics or conditions that increase susceptibility to AKI may include dehydration or volume depletion, advanced age, Black race, and diabetes mellitus among others. Critical illness itself is also a risk factor for AKI; other exposures that may increase the risk of AKI in susceptible individuals include sepsis (reported to account for ≥ 50% of cases in intensive care units), shock, rhabdomyolysis, and exposure to nephrotoxic medications, among others.
• AKI in critical illness has a heterogeneous clinical course, but is associated with an increased risk of poor long-term outcomes (including in patients with apparent full recovery) and an increased risk of death (35%-60% in-hospital mortality reported in patients requiring kidney replacement therapy), cardiovascular events, and development or progression to chronic kidney disease.

Monitoring in Patients With Critical Illness

• Monitor serum creatinine and urine output of all patients until recovery from critical illness and amelioration of any other risk factors for acute kidney injury (AKI).
• The frequency and duration monitoring should be according to clinical judgement based on the patient's individual risk and clinical course.
  • Consider assessing serum creatinine at least once daily in patients with a critical illness, and more frequently after a relevant exposure.
  • Consider continuous urine output monitoring, including with bladder catheterization if appropriate and considering the risk of infection.
• When evaluating serum creatinine and urine output, clinical context should be considered before diagnosing AKI as both markers are also affected by non-glomerular filtration rate factors.
• Various methods have been proposed to detect subclinical AKI (early dysfunction masked by kidney functional reserve and/or long half life of creatinine) including novel biomarkers, clinical prediction models, and various functional tests, among others.

Diagnosis

• Acute kidney injury (AKI) is commonly diagnosed using KDIGO classification system, which defines AKI as any of the following:
  • increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 mcmol/L) within 48 hours
  • increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within prior 7 days
  • urine volume < 0.5 mL/kg/hour for 6 hours
• Evaluate patients with critical illness and AKI for prerenal azotemia, acute tubular necrosis, intrinsic renal pathology, and postrenal obstruction.
• The initial evaluation may include:
  • testing for serum urea and creatinine
  • assessment of urine output and response to intravascular fluid bolus
  • assessment of urine electrolytes for calculation of fractional excretion of sodium or urea
  • urinalysis and urine sediment to assess for granular casts, red cell or white cell casts
  • bladder scan or renal ultrasound to assess for postrenal obstruction.

Supportive Care for Prevention and Management

• Prevention and management of acute kidney injury (AKI) in critical illness entail recommended kidney-protective supportive care and continual kidney function monitoring. There are no specific drugs or therapies used to prevent or treat AKI; any identified underlying causes in patients with AKI should be managed according to standards of care.
• Avoid nephrotoxic agents, and be aware of special considerations if contrast agents are required. Once AKI is diagnosed, discontinue, adjust, or cease nephrotoxic medications if possible.
• Support renal perfusion through optimization of hemodynamics for prevention and treatment of AKI.
  • Generally use crystalloid solutions as first-line fluids in patients with critical illness, and avoid routine use of colloids (such as 20%-25% albumin, hydroxyethyl starches, or dextrans) due to risk of kidney injury (Strong recommendation).
  • Use a vasopressor (norepinephrine is first-line) in conjunction with fluids in patients with vasomotor shock with or at risk for acute kidney injury (AKI) (Strong recommendation).
  • Consider individualizing target mean arterial pressure (MAP) when premorbid blood pressure is available; generally a target of ≥ 65 mm Hg is typically used in clinical practice.
  • In patients with septic shock, consider MAP target 65-70 mm Hg, except in patients with chronic hypertension in whom consider a target of 80-85 mm Hg (Weak recommendation).
  • Do not use low-dose dopamine to prevent or treat AKI (Strong recommendation).
  • The following vasodilators are also not suggested to prevent or treat AKI:
    • fenoldopam (Weak recommendation)
    • atrial natriuretic peptide (Weak recommendation)
    • levosimendan in patients with sepsis, or receiving cardiac surgery with poor preoperative left ventricular function or requiring postoperative hemodynamic support (Weak recommendation)
• Do not use diuretics for routine prevention or treatment of AKI (Strong recommendation), but consider reserving diuretic use for patients with volume overload (Weak recommendation).
• Assess for complications as soon as AKI is detected to allow for early treatment. Early complications include metabolic acidosis, volume overload, electrolyte disturbances (hyperkalemia in particular), uremia, and medication toxicities.
• Nutritional support for patients with an AKI:
  • Consider total energy intake of 20-30 kcal/kg/day in patients with any stage of AKI (Weak recommendation);
  • Consider avoiding protein restriction as means of preventing or delaying initiation of kidney replacement therapy (KRT) (Weak recommendation)
  • Consider nutrition via enteral route as preferred option (Weak recommendation).
• Consider follow-up with a multidisciplinary recovery-focused care team at rehabilitation/skilled nursing facilities and close monitoring for patients recovering from a critical illness and an AKI. After recovery, care should include preventive strategies to avoid long-term complications (such as increased risk of death, cardiovascular events, and chronic kidney disease).

Kidney Replacement Therapy (KRT)

• Consider initiating KRT if life-threatening changes in fluid, electrolyte, and/or acid-base balance occur.
• For nonurgent situations, consider the entire clinical scenario including presence of KRT-modifiable factors and trends of laboratory tests when deciding to start KRT instead of relying on blood urea nitrogen (BUN) and creatinine thresholds alone.
  • The decision to start KRT incorporates a spectrum of clinical information including social and cultural factors, severity and duration of AKI, global prognosis and potential for recovery, risk of KRT complications, and metabolic and fluid demands/kidney capacity balance assessment (exact methods for determining demand and capacity are unknown) among others.
  • Consider a shared decision-making approach similar to care prior to KRT, with clear communication and care decisions being focused on the patient and/or the patient's family/next of kin (and multidisciplinary end-of-life care team if applicable), including patient preferences and goals of care.
• Optimal timing of KRT initiation is unknown, as criteria for initiating KRT is highly heterogeneous. Early initiation of KRT (before the development of urgent indications) does not appear to reduce mortality in critically ill patients with acute kidney injury based on systematic reviews and the majority of randomized trials.
• Higher volumes of continuous venovenous hemodiafiltration (> 30 mL/kg/hour) do not appear to improve survival or renal function.
• Stop KRT when a satisfactory kidney recovery is reached or when it no longer meets the goals of care.
• Consider follow-up with a multidisciplinary recovery-focused care team at rehabilitation/skilled nursing facilities and close monitoring for patients recovering from a critical illness and AKI. After recovery, care should include preventive strategies to avoid long-term complications (such as increased risk of death, cardiovascular events, and chronic kidney disease).