What is the appropriate evaluation and management of acute kidney injury?

Evaluation and Management of Acute Kidney Injury

Immediately discontinue all nephrotoxic medications—including NSAIDs, ACE inhibitors, ARBs, diuretics, aminoglycosides, and contrast agents—as this is the single most critical intervention to prevent progression of AKI. 1, 2

Diagnosis and Staging

KDIGO Diagnostic Criteria

• AKI is diagnosed when any one of the following occurs: serum creatinine rise ≥0.3 mg/dL within 48 hours, creatinine increase ≥1.5× baseline within 7 days, or urine output <0.5 mL/kg/hour for ≥6 consecutive hours 1
• Stage the severity using KDIGO criteria:
  • Stage 1: Creatinine 1.5–1.9× baseline or ≥0.3 mg/dL rise, or urine output <0.5 mL/kg/h for >6 hours 1
  • Stage 2: Creatinine 2.0–2.9× baseline, or urine output <0.5 mL/kg/h for >12 hours 1
  • Stage 3: Creatinine ≥3.0× baseline or ≥4.0 mg/dL with acute rise ≥0.3 mg/dL, or urine output <0.3 mL/kg/h for ≥24 hours, or initiation of RRT 1
• Even a modest 0.3 mg/dL creatinine rise carries an approximately four-fold increase in hospital mortality, so do not dismiss small absolute increases as clinically insignificant 1

Initial Laboratory Evaluation

• Obtain comprehensive metabolic panel (sodium, potassium, calcium, magnesium, chloride, bicarbonate, BUN, creatinine) immediately to identify life-threatening electrolyte derangements 1
• Measure serum creatinine and electrolytes every 4–6 hours initially in Stage 2–3 AKI to track progression 1, 3
• Perform urinalysis with microscopy to identify casts: muddy-brown casts suggest acute tubular necrosis, red-cell casts indicate glomerulonephritis, white-cell casts point to interstitial nephritis 1
• Check urine sodium and fractional excretion of sodium: urine sodium <20 mEq/L (or FENa <1%) favors prerenal azotemia; urine sodium >40 mEq/L (or FENa >2%) supports intrinsic renal injury 1
• Obtain renal ultrasound to exclude obstructive (postrenal) causes and assess kidney size 1

Immediate Management Algorithm

Step 1: Medication Review and Discontinuation

• Stop all nephrotoxic drugs immediately: NSAIDs, ACE inhibitors, ARBs, diuretics, aminoglycosides, vancomycin, contrast media, and chemotherapeutic agents 1, 2
• The "triple whammy" combination (NSAID + diuretic + ACE-I/ARB) more than doubles AKI risk and must be discontinued 4, 2
• Each additional nephrotoxin increases AKI odds by 53%, so avoid poly-nephrotoxic regimens 4, 2
• Review all prescription and over-the-counter medications to identify hidden nephrotoxins 2

Step 2: Classify AKI Etiology

• Categorize as prerenal (volume depletion, low cardiac output, drugs affecting glomerular hemodynamics), intrinsic renal (acute tubular necrosis, glomerulonephritis, interstitial nephritis, atheroembolic disease), or postrenal (urinary tract obstruction) 1, 2
• Prerenal AKI typically resolves within 48 hours after plasma-volume expansion and removal of precipitating factors, whereas acute tubular necrosis requires supportive care and does not improve with fluids alone 2

Step 3: Volume Assessment and Fluid Management

• Assess volume status through clinical examination (jugular venous pressure, skin turgor, mucous membranes, orthostatic vital signs) and consider central venous pressure monitoring when clinical assessment is unclear 4, 1
• For hypovolemic patients: provide isotonic crystalloids—preferably balanced solutions like lactated Ringer's over 0.9% saline—to prevent metabolic acidosis and hyperchloremia 4, 2, 5
• Avoid hydroxyethyl starches because they worsen kidney injury and increase mortality in critically ill patients 4, 2, 5
• Use dynamic indices (passive leg-raising test, pulse/stroke volume variation) rather than static measurements to guide fluid therapy 4, 2
• Avoid excessive fluid administration that leads to volume overload, as fluid overload >10–15% body weight is associated with adverse outcomes 4, 2

Step 4: Hemodynamic Support

• Target mean arterial pressure ≥65 mmHg to ensure adequate renal perfusion 4, 2
• Norepinephrine is the preferred first-line vasopressor when hypotension persists after adequate fluid resuscitation 2, 5
• Consider earlier use of vasoactive medications instead of excessive fluid administration for hypotension 4, 2
• Do not use dopamine to prevent or treat AKI—it is ineffective based on Level 1A evidence 2, 5

Step 5: Infection Screening and Treatment

• Obtain blood cultures, urine cultures, and chest radiograph when infection is suspected 1
• For cirrhotic patients, perform diagnostic paracentesis to rule out spontaneous bacterial peritonitis 1, 2
• Start empiric broad-spectrum antibiotics immediately when infection is strongly suspected, without awaiting culture results 1, 2

Special Population: Cirrhotic Patients

Immediate Actions

• Discontinue both diuretics AND beta-blockers (not just diuretics) in cirrhotic patients with AKI 2, 3
• Administer intravenous albumin 1 g/kg (maximum 100 g) daily for two consecutive days when serum creatinine has doubled from baseline 1, 2
• A fall in creatinine to within 0.3 mg/dL of baseline after 48 hours of albumin indicates prerenal AKI 2

Stage-Based Treatment

• Stage 1A AKI (creatinine rise ≥0.3 mg/dL but <1.5 mg/dL): Monitor creatinine every 2–4 days; do not initiate vasoconstrictors until creatinine reaches ≥1.5 mg/dL 2
• Stage 1B/2–3 AKI (creatinine ≥1.5 mg/dL): If no improvement after 48 hours of albumin and hepatorenal syndrome criteria are met, start vasoconstrictor therapy (terlipressin preferred; or norepinephrine; or midodrine + octreotide) together with albumin 1, 2

Management of Complications

Electrolyte Abnormalities

• Correct hyperkalemia urgently when present—this may require insulin/glucose, calcium gluconate, sodium bicarbonate, or dialysis 1
• In adults with severe metabolic acidosis, administer intravenous sodium bicarbonate; consider dialysis when acidosis is refractory to medical therapy 1

Fluid Overload

• Monitor for signs of volume overload: peripheral edema, pulmonary congestion, weight gain 3
• Implement fluid restriction for volume-overloaded patients 3

Renal Replacement Therapy (RRT)

Indications for Urgent RRT

• Severe oliguria unresponsive to fluid resuscitation 1, 3
• Refractory hyperkalemia 1, 2
• Severe, intractable metabolic acidosis 1, 2
• Volume overload causing pulmonary edema 1, 2
• Uremic complications (encephalopathy, pericarditis) 1, 2

RRT Management

• Individualize timing of RRT based on overall clinical condition rather than specific creatinine or BUN thresholds 2, 5
• Reassess the need for continued RRT daily 1, 3
• Patients with Stage 3 AKI requiring RRT have approximately four-fold higher in-hospital mortality compared with lower AKI stages 1

Nephrology Consultation

Obtain nephrology consultation when:

• The underlying cause of AKI cannot be identified after initial evaluation 1
• AKI persists for more than 48 hours despite appropriate initial management 1, 2
• Stage 3 AKI or pre-existing CKD stage 4 or higher is present 1
• Glomerulonephritis, vasculitis, or rapidly progressive AKI is suspected 2

Follow-Up After AKI

• Reassess kidney function at 3 months after an AKI episode to determine progression to chronic kidney disease 2
• Patients with Stage 3 AKI require earlier follow-up within 1–2 weeks because of higher risk of CKD progression 2
• Individuals with pre-existing CKD, heart failure, liver disease, or active malignancy need more intensive post-AKI monitoring 2
• Document the AKI episode clearly in the medical record and educate patients to avoid NSAIDs and seek prompt medical attention for intercurrent illnesses 2

Common Pitfalls to Avoid

• Delaying RRT when clear indications exist increases mortality 1, 3
• Failing to identify and address the underlying cause leads to continued kidney damage 1, 3
• Inappropriate continuation of nephrotoxic medications during AKI recovery can cause re-injury 4, 1, 3
• Overly aggressive fluid administration in non-hypovolemic patients worsens outcomes 2, 3
• Using loop diuretics to prevent or treat AKI provides no benefit and may cause harm 2, 5
• Dismissing modest absolute creatinine rises in CKD patients as insignificant—the KDIGO absolute criterion (≥0.3 mg/dL) captures clinically relevant AKI across all baseline renal functions 1
• Continuing diuretics after AKI diagnosis worsens outcomes and delays renal recovery 2