What are the guidelines for Acute Kidney Injury (AKI) in sepsis?

From the Guidelines

Sepsis-associated acute kidney injury (AKI) should be managed with early recognition, prompt treatment of the underlying infection, and supportive care, with consideration of renal replacement therapy (RRT) for severe AKI, as recommended by the Surviving Sepsis Campaign guidelines 1.

Key Considerations

• Early recognition and treatment of sepsis are crucial to prevent AKI, with empiric broad-spectrum antibiotics started within one hour of sepsis recognition, using agents like piperacillin-tazobactam, meropenem, or cefepime plus vancomycin, adjusted based on local resistance patterns and patient factors.
• Maintain adequate perfusion with crystalloid fluid resuscitation (30 ml/kg within the first 3 hours) and vasopressors if needed, with norepinephrine as first-line (starting at 0.05 mcg/kg/min, titrating up to 0.5 mcg/kg/min), targeting a mean arterial pressure of 65-70 mmHg to ensure renal perfusion.
• Monitor kidney function closely with serial creatinine measurements, urine output (targeting >0.5 ml/kg/hr), and fluid balance, avoiding nephrotoxic medications when possible, including NSAIDs, aminoglycosides, and contrast agents, and adjusting medication dosing based on estimated GFR.

Renal Replacement Therapy (RRT)

• Consider RRT for severe AKI with refractory acidosis (pH <7.15), hyperkalemia (>6.5 mEq/L), fluid overload (>10% of body weight), or uremic symptoms, with continuous RRT often preferred in hemodynamically unstable patients, as suggested by the KDIGO guidelines 1.
• The choice of RRT modality, either continuous or intermittent, should be based on the individual patient's needs and clinical context, with consideration of factors such as hemodynamic stability, fluid balance, and electrolyte management.

Additional Recommendations

• Use isotonic crystalloids rather than colloids (albumin or starches) as initial management for expansion of intravascular volume in patients at risk for AKI or with AKI, as recommended by the KDIGO guidelines 1.
• Avoid the use of diuretics to prevent or treat AKI, except in the management of volume overload, and consider the use of protocol-based management of hemodynamic and oxygenation parameters to prevent the development or worsening of AKI in high-risk patients.

From the Research

Guidelines for Acute Kidney Injury (AKI) in Sepsis

• Prevention of AKI in sepsis starts with early and ample fluid resuscitation, preferentially with crystalloid solutions 2
• Balanced crystalloids have no proven superior benefit over other crystalloid solutions 2
• Renal function can be evaluated by measuring lactate clearance rate, renal Doppler, or central venous oxygenation monitoring 2
• Assuring sufficiently high central venous oxygenation is crucial in preventing AKI, especially in the post-operative setting 2
• Noradrenaline is the vasopressor of choice for preventing AKI in sepsis 2, 3
• Intra-abdominal hypertension should not be neglected in sepsis as it can trigger AKI in post-operative and trauma patients 2
• Early renal replacement therapy (RRT) is recommended in fluid-overloaded patients who are refractory to diuretics, but compelling evidence about its usefulness is still lacking 2
• Continuous RRT (CRRT) is advocated as the preferred modality in hemodynamically unstable AKI, although convincing data is limited 2
• Diuretics should be avoided in the absence of hypervolemia 2
• Antimicrobial dosing during CRRT needs to be thoroughly reconsidered to assure adequate infection control 2

Hemodynamic Predictors for Sepsis-Induced AKI

• Sequential organ failure assessment (SOFA score) and cardiovascular SOFA score can predict sepsis-induced AKI 4
• Persistent low stroke volume index (SVI) and global end-diastolic index (GEDI) after initial fluid resuscitation can predict oliguria/anuria at 24 hours 4
• Combination of higher vasopressor dependency index (VDI) and norepinephrine, lower systemic vascular resistance index (SVRI), and mean arterial blood pressure (MAP) levels can indicate severe vasoplegia and higher risk of sepsis-induced AKI 4

Pathogenesis and Treatment of Septic AKI

• Septic AKI is associated with microvascular abnormalities and tubular stress, and renal medullary hypoxia due to redistribution of intra-renal perfusion is a critical mediator of septic AKI 5
• Vasopressor drugs, such as norepinephrine, remain the cornerstone of therapy for maintenance of blood pressure and organ perfusion, but may have limited effectiveness in septic AKI 5
• Vasopressin, angiotensin II, and α2-adrenergic receptor agonists (clonidine and dexmedetomidine) may be feasible adjunct therapies for catecholamine-resistant vasodilatory shock 5

Fluid Resuscitation in Septic AKI

• Fluid resuscitation is the initial cornerstone of treatment for septic AKI, but its effectiveness remains uncertain 6
• The type and amount of fluid used for resuscitation may affect renal perfusion and oxygen delivery, and starch-containing fluids may be nephrotoxic 3
• Chloride-rich fluids may also adversely affect renal function, and the use of vasoactive drugs, such as norepinephrine and vasopressin, may have variable effects on renal function in septic AKI 3