What is the recommended diagnosis and management of acute kidney injury (AKI) in a hemodynamically unstable intensive care unit (ICU) patient with sepsis and possible nephrotoxic drug exposure?

Management of Acute Kidney Injury in ICU Patients

Immediate Diagnostic Approach

In a hemodynamically unstable ICU patient with sepsis and possible nephrotoxic exposure, immediately initiate aggressive sepsis resuscitation with at least 30 mL/kg isotonic crystalloids within 3 hours while simultaneously withdrawing all nephrotoxic agents, as survival takes absolute priority over concerns about fluid overload or medication nephrotoxicity. 1, 2

Define AKI Using KDIGO Criteria

• AKI is defined by serum creatinine increase ≥0.3 mg/dL within 48 hours OR increase to ≥1.5 times baseline within 7 days OR urine output <0.5 mL/kg/hr for 6 hours 3, 4
• Stage 1: SCr 1.5-1.9× baseline or ≥0.3 mg/dL increase; urine output <0.5 mL/kg/hr for 6-12 hours 3
• Stage 2: SCr 2.0-2.9× baseline; urine output <0.5 mL/kg/hr for ≥12 hours 3
• Stage 3: SCr ≥3.0× baseline or ≥4.0 mg/dL or initiation of RRT; urine output <0.3 mL/kg/hr for ≥24 hours or anuria for ≥12 hours 3

Perform Risk Stratification

• Conduct a kidney health assessment (KHA) evaluating: previous AKI episodes, chronic kidney disease, blood pressure, current medications, and dipstick proteinuria 3
• In septic patients, assess for multiple nephrotoxic exposures—each additional nephrotoxin increases AKI odds by 53%, and combining 3+ nephrotoxins doubles AKI risk 1
• Consider biomarker testing with TIMP-2 × IGFBP7 if available, as values ≥0.3 (ng/mL)²/1000 predict AKI development and identify patients who benefit from protocolized preventive care 3

Hemodynamic Management and Resuscitation

Fluid Administration Strategy

• Administer at least 30 mL/kg of isotonic crystalloids within the first 3 hours targeting mean arterial pressure (MAP) ≥65 mmHg 1, 2
• Use isotonic crystalloids (normal saline or balanced solutions) rather than colloids for initial volume expansion—avoid albumin and starches in AKI as they increase risk without improving outcomes 1, 2
• Once hemodynamically stable, avoid overzealous fluid administration as volume overload worsens outcomes 1, 2
• Do not under-resuscitate due to fear of volume overload, as inadequate resuscitation worsens both sepsis-associated AKI and mortality 2

Vasopressor Management

• Initiate vasopressors in conjunction with fluids for vasomotor shock to maintain MAP ≥65 mmHg 1, 2
• Norepinephrine is the first-line vasopressor; vasopressin may be added as adjunctive therapy if MAP remains <65 mmHg despite adequate norepinephrine dosing 1, 2
• Target MAP ≥65 mmHg consistently—this is the primary hemodynamic goal in septic shock with AKI 1, 2

Source Control and Antimicrobial Therapy

• Obtain blood cultures and initiate broad-spectrum antibiotics within 1 hour of septic shock recognition 1, 2
• Do not withhold antibiotics due to nephrotoxicity concerns—treatment of sepsis takes absolute priority over renal considerations, as survival benefit outweighs nephrotoxicity risk 1, 2
• If vancomycin is indicated for suspected MRSA or resistant gram-positive organisms, initiate immediately despite AKI 1
• Ensure adequate resuscitation before attributing worsening renal function to vancomycin 1

Nephrotoxin Management

Immediate Medication Review

• Withdraw ALL nephrotoxic drugs immediately: NSAIDs, aminoglycosides (unless no alternative exists), ACE inhibitors/ARBs, and contrast agents 3, 1
• Reduce or withdraw diuretic therapy in Stage 1 AKI 3
• Review all medications including over-the-counter drugs 3
• Adjust all renally-cleared medications for decreased GFR 1

Drug Burden Assessment

• Conduct systematic drug burden assessment to identify which nephrotoxic drug combinations are present 3
• Avoid combining multiple nephrotoxins—the cumulative effect is multiplicative, not additive 1

Renal Replacement Therapy Decision-Making

Indications for RRT Initiation

Initiate RRT only for definitive indications: severe acidosis (pH <7.15), hyperkalemia refractory to medical management, uremic complications (pericarditis, encephalopathy, bleeding), or refractory volume overload causing pulmonary edema 1, 2

• Do not initiate RRT solely for creatinine elevation or oliguria without other definitive indications 1, 2
• The timing of RRT remains controversial—early initiation based on biomarkers alone has not shown mortality benefit 3

RRT Modality Selection

• Use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis for hemodynamically unstable septic patients, as CRRT facilitates fluid balance management during aggressive resuscitation 1, 2
• CRRT allows for gradual fluid removal and better hemodynamic tolerance in vasopressor-dependent patients 1, 2
• Consider intermittent hemodialysis only once hemodynamically stable 1

Metabolic and Supportive Management

Acid-Base Management

• Do not use sodium bicarbonate to improve hemodynamics or reduce vasopressor requirements if pH ≥7.15—bicarbonate therapy has not shown benefit and may cause harm 1, 2
• Reserve bicarbonate for severe metabolic acidosis (pH <7.15) with definitive RRT indication 1

Glycemic Control

• Target blood glucose ≤180 mg/dL using protocolized insulin therapy 1, 2
• Avoid tight glycemic control (≤110 mg/dL) as it increases hypoglycemia risk without mortality benefit 1, 2
• Monitor glucose every 1-2 hours until stable, then every 4 hours 2

Thromboprophylaxis and Stress Ulcer Prevention

• Administer pharmacologic VTE prophylaxis with low-molecular-weight heparin (LMWH) unless contraindicated 1, 2
• Use dalteparin or another LMWH with low renal metabolism, or switch to unfractionated heparin if creatinine clearance <30 mL/min 2
• Provide stress ulcer prophylaxis with proton pump inhibitor or H2-receptor antagonist for patients with GI bleeding risk factors 1

Nutritional Support

• Initiate early enteral nutrition (preferentially over parenteral) within 48 hours if tolerated 1
• Target 20-30 kcal/kg/day total energy intake 1
• Provide 1.0-1.5 g/kg/day protein; increase to 1.7 g/kg/day if on CRRT or hypercatabolic 1

Monitoring Strategy

Serial Assessment Parameters

• Monitor serum creatinine, urine output, and fluid balance every 4-6 hours 1
• Track lactate clearance as a marker of adequate resuscitation 1
• Reassess AKI stage progression—patients not responding to initial management require escalation to Stage 2/3 protocols 3

Stage-Specific Management Algorithm

For Stage 1 AKI:

• Withdraw diuretics and nephrotoxins 3
• Expand plasma volume with crystalloids or albumin if clinically hypovolemic 3
• Monitor closely for progression 3

For Stage 2-3 AKI (or Stage 1 with progression):

• Administer intravenous albumin at 1 g/kg bodyweight per day for two consecutive days to treat prerenal AKI and allow differential diagnosis 3
• If no response after albumin trial and other causes excluded, consider hepatorenal syndrome or other specific AKI phenotypes requiring targeted therapy 3
• Prepare for RRT if definitive indications develop 1, 2

Critical Pitfalls to Avoid

• Do not delay antibiotics or adequate fluid resuscitation due to concerns about nephrotoxicity or volume overload—inadequate treatment of sepsis is the primary driver of mortality 1, 2
• Do not use biomarkers of acute kidney damage (NGAL, KIM-1) for risk assessment prior to a kidney insult—these are only interpretable after injury has occurred 3
• Avoid subclavian catheters if possible to preserve future vascular access 3
• Do not assume oliguria always indicates hypovolemia—multiple etiologies exist beyond hypovolemia, and inappropriate volume administration can cause fluid overload 3
• Recognize that AKI is heterogeneous—congestive heart failure and dehydration produce identical creatinine changes but require opposite treatments 5