How to manage a patient with acute kidney injury (AKI) and sepsis?

Management of AKI with Sepsis

In septic patients with AKI, immediately initiate aggressive fluid resuscitation with at least 30 mL/kg of crystalloid within 3 hours, start broad-spectrum antibiotics within 1 hour, use norepinephrine to maintain MAP ≥65 mmHg if hypotension persists despite fluids, and consider continuous renal replacement therapy only for definitive indications such as refractory volume overload, severe acidosis, or hyperkalemia. 1, 2

Immediate Resuscitation Protocol (First 3 Hours)

Fluid Resuscitation

• Administer at least 30 mL/kg of isotonic crystalloid solution within the first 3 hours of sepsis recognition 2
• Use crystalloids rather than colloids (albumin, hydroxyethyl starch), as colloids increase AKI risk without improving outcomes 2
• Avoid normal saline in large volumes due to hyperchloremic metabolic acidosis; balanced crystalloids are preferred though not definitively superior 1, 3
• Critical pitfall: Do not under-resuscitate due to fear of volume overload—inadequate resuscitation worsens both sepsis-associated AKI and mortality 2

Antibiotic Administration

• Obtain blood cultures immediately, but never delay antibiotics beyond 1 hour of sepsis recognition 2, 4
• Administer full loading doses regardless of renal function—loading doses depend on volume of distribution, not kidney function 4
• For vancomycin: give 25-30 mg/kg loading dose based on actual body weight, targeting trough levels of 15-20 mg/L 4
• Use extended infusions (2-4 hours) for beta-lactams rather than standard 30-minute boluses to optimize pharmacodynamics 4, 5

Hemodynamic Management

Vasopressor Support

• Use norepinephrine as first-line vasopressor if MAP remains <65 mmHg despite adequate fluid resuscitation 1, 2
• Target MAP ≥65 mmHg consistently 1, 2
• Avoid dopamine as first-line agent—it is associated with increased mortality and arrhythmias in septic shock 1
• Vasopressin may be added in less severely ill patients but shows no mortality benefit in severe sepsis 1

Protocol-Based Management

• Implement early goal-directed therapy protocols targeting hemodynamic parameters and tissue oxygenation 1
• Monitor central venous oxygenation, lactate clearance, and urine output to assess adequacy of resuscitation 3
• Important caveat: Only use protocols that have been previously validated; de novo protocols should be tested in clinical trials first 1

Renal Replacement Therapy Decision-Making

Indications for RRT Initiation

• Initiate RRT only for definitive indications 2:
  • Refractory volume overload despite diuretics
  • Severe metabolic acidosis
  • Hyperkalemia unresponsive to medical management
  • Uremic complications (pericarditis, encephalopathy)
• Do not initiate RRT solely based on creatinine level or AKI stage 1

RRT Modality Selection

• Use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis in hemodynamically unstable patients 1, 2, 4
• CRRT facilitates fluid balance management during aggressive resuscitation and causes less hemodynamic instability 2, 4
• Prolonged intermittent RRT (PIRRT) is a reasonable alternative to CRRT in hemodynamically unstable adults 1

Supportive Management

Glycemic Control

• Target blood glucose 110-149 mg/dL (6.1-8.3 mmol/L) using protocolized insulin therapy 1
• Avoid tight glycemic control (<110 mg/dL) as it increases hypoglycemia risk without benefit 1, 2
• Monitor glucose every 1-2 hours until stable, then every 4 hours 2

Nutritional Support

• Provide total energy intake of 20-30 kcal/kg/day 1
• Administer protein: 0.8-1.0 g/kg/day in non-catabolic AKI without dialysis, 1.0-1.5 g/kg/day in patients on RRT, up to 1.7 g/kg/day in hypercatabolic patients on CRRT 1
• Do not restrict protein to delay RRT initiation—this is ineffective and potentially harmful 1
• Provide nutrition preferentially via enteral route 1

Reassessment for Persistent AKI

When AKI Persists Beyond 48-72 Hours

• Reassess the underlying etiology—consider multifactorial causes including ongoing sepsis, nephrotoxins, or unrecognized obstruction 1
• Perform additional diagnostic tests: urine sediment analysis, proteinuria assessment, renal ultrasound 1
• Re-evaluate hemodynamic status, volume status, and kidney perfusion adequacy 1
• Consider nephrology consultation if etiology is unclear or subspecialist care is needed 1
• Use timed urine creatinine clearance to estimate kidney function in steady state—eGFR equations validated for CKD are inaccurate in AKI 1

Critical Pitfalls to Avoid

• Never withhold or delay antibiotics due to nephrotoxicity concerns—treating sepsis takes absolute priority over renal considerations 2
• Never reduce loading doses of antibiotics due to renal dysfunction—this leads to subtherapeutic levels and treatment failure 4
• Avoid overzealous fluid resuscitation in specific contexts (e.g., malaria-induced AKI) where it may worsen acute lung injury 1
• Do not use dopamine for AKI prevention—it is ineffective and potentially harmful 1
• Avoid nephrotoxic agents when possible—each additional nephrotoxin increases AKI odds by 53% 5