Causes and Management of Acute Kidney Injury
Definition and Diagnosis
AKI is diagnosed when serum creatinine increases by ≥0.3 mg/dL within 48 hours, increases ≥50% from baseline within 7 days, or urine output decreases to <0.5 mL/kg/hour for 6 hours 1, 2. Stage the severity using KDIGO criteria (Stage 1-3), with Stage 3 representing the most severe form requiring intensive intervention 2.
Causes of AKI: The Three Categories
Prerenal AKI (Volume-Responsive)
- Most common cause in hospitalized patients, resulting from inadequate renal perfusion 1, 3
- Triggers include:
Intrinsic Renal AKI
- Acute tubular necrosis (ATN) from prolonged ischemia or nephrotoxic exposures 1, 3
- Nephrotoxic medications: aminoglycosides, NSAIDs, contrast agents 2, 4
- Sepsis-associated AKI (most common in ICU settings) 1
- Glomerulonephritis or interstitial nephritis 3
- Rare causes requiring specialist consultation: tumor lysis syndrome, thrombotic thrombocytopenic purpura, cholesterol embolization 1
Postrenal AKI (Obstructive)
- Occurs rarely but must be excluded early 1, 3
- Causes include prostatic hypertrophy, urethral stricture, bilateral ureteral obstruction, or bladder outlet obstruction 3, 5
Immediate Management: The First 24 Hours
Step 1: Discontinue Nephrotoxic Agents
Immediately stop all nephrotoxic medications including NSAIDs, aminoglycosides, ACE inhibitors, ARBs, and diuretics 2, 6. The "triple whammy" combination of NSAIDs, diuretics, and ACE inhibitors/ARBs more than doubles AKI risk 6. Adjust all medication dosages based on current estimated GFR 2, 6.
Step 2: Identify the Underlying Cause
- Obtain detailed history focusing on recent medication changes, volume losses, hypotensive episodes, and nephrotoxic exposures 3, 7
- Perform urinalysis with microscopy to detect casts, cells, or protein 1, 3
- Check urine sodium and fractional excretion of sodium to differentiate prerenal from intrinsic causes 1
- Obtain renal ultrasound immediately to rule out obstruction, especially in older males with prostatic symptoms 2, 3
- Perform rigorous infection workup in ALL patients: blood cultures, urine cultures, chest radiograph, and diagnostic paracentesis if ascites present 1, 6
Step 3: Optimize Volume Status and Hemodynamics
- Assess volume status through clinical examination (jugular venous pressure, skin turgor, mucous membranes, orthostatic vital signs) 2, 3
- For hypovolemic patients: administer isotonic crystalloids (normal saline or lactated Ringer's) rather than colloids 2, 3
- Avoid hypotonic fluids which worsen hyponatremia 6
- Maintain mean arterial pressure >65 mmHg to ensure adequate renal perfusion 2
- Monitor with strict input/output measurements 6, 3
Stage-Specific Management
Stage 1 AKI
- Continue nephrotoxic medication discontinuation and volume optimization 3
- Monitor serum creatinine and electrolytes daily 3
- Reassess medication dosing requirements 3
Stage 2 AKI
- Intensify monitoring to every 4-6 hours for creatinine, BUN, and electrolytes 2, 6
- Increase frequency of clinical assessments for fluid overload 3
- Prepare for potential need for renal replacement therapy 3
Stage 3 AKI
- Monitor electrolytes, BUN, and creatinine every 4-6 hours 2, 6
- Urgent indications for renal replacement therapy (RRT) include 2, 6:
- Severe oliguria unresponsive to fluid resuscitation
- Refractory hyperkalemia
- Severe metabolic acidosis (pH <7.1)
- Volume overload unresponsive to diuretics
- Uremic complications (pericarditis, encephalopathy, bleeding)
- Certain toxin ingestions
- Reassess need for continued RRT daily 2, 6
Special Population: AKI in Cirrhosis
Hepatorenal Syndrome-AKI (HRS-AKI)
When serum creatinine remains >2× baseline despite volume repletion, initiate HRS-AKI treatment 1:
- Albumin 1 g/kg IV on day 1 (maximum 100 g), then 20-40 g daily 1, 2
- Add vasoactive agents: terlipressin 1 mg IV every 4-6 hours (increase to 2 mg if needed); if unavailable, use octreotide plus midodrine or norepinephrine 1, 2
- Continue treatment until creatinine returns to within 0.3 mg/dL of baseline for 2 consecutive days or for maximum 14 days 1
Cirrhosis-Specific Interventions
- Perform diagnostic paracentesis in ALL cirrhotic patients with AKI to evaluate for spontaneous bacterial peritonitis 1, 6
- Hold diuretics and nonselective beta-blockers immediately 1
- Administer albumin 1 g/kg/day for 2 days if creatinine doubles from baseline 1, 2
- Start broad-spectrum antibiotics when infection is suspected (no role for routine prophylaxis) 1
Management of Complications
Electrolyte Abnormalities
- Hyperkalemia: may require urgent intervention with calcium gluconate, insulin/glucose, sodium bicarbonate, or dialysis 2
- Hyponatremia: correct slowly (no faster than 8-10 mEq/L per 24 hours) to prevent osmotic demyelination syndrome 6
- Monitor for signs of electrolyte imbalance: muscle weakness, arrhythmias, altered mental status 5
Fluid Overload
- Watch for peripheral edema, pulmonary congestion, and weight gain 6, 3
- Avoid diuretics in acute phase unless volume overload is present, as they can worsen prerenal AKI 1, 2
- If diuretics are necessary, furosemide carries risk of electrolyte depletion and ototoxicity, especially with aminoglycosides 5, 4
Prevention Strategies
High-Risk Patient Identification
Patients at increased risk include those with 2, 3:
- Advanced age
- Pre-existing chronic kidney disease (especially stage 4 or higher)
- Diabetes mellitus
- Heart failure
- Sepsis or critical illness
- Recent contrast exposure
Preventive Measures
- Avoid NSAIDs entirely in at-risk patients 1, 2
- Avoid excessive or unmonitored diuretic use 1
- Provide albumin replacement with large-volume paracentesis (>5 liters) 1
- Ensure adequate hydration before contrast procedures 2
- Implement pharmacist-led medication review programs to identify nephrotoxic exposures 2, 6
Follow-Up and Long-Term Management
Post-Discharge Care
- Schedule close clinical evaluation within 3 months for patients with Stage 2-3 AKI to assess for resolution, new-onset CKD, or worsening of pre-existing CKD 2, 3
- Even a single AKI episode increases risk of cardiovascular disease, chronic kidney disease, and death 7
- Provide patient education on avoiding over-the-counter NSAIDs and recognizing symptoms of worsening kidney function 2, 6
Ongoing Monitoring
- Continue to adjust medication dosages as kidney function changes during recovery 6
- Monitor for development of chronic kidney disease 3
- Risk stratify based on AKI severity to guide timing of nephrology follow-up 2
Critical Pitfalls to Avoid
- Delaying RRT when clear indications exist increases mortality 2, 6
- Continuing nephrotoxic medications during AKI recovery causes ongoing kidney damage 2, 6
- Overly aggressive fluid administration in non-hypovolemic patients worsens outcomes 6
- Failing to identify and treat underlying infection leads to persistent AKI 1, 6
- Overly rapid correction of hyponatremia causes osmotic demyelination syndrome 6
- Using aminoglycosides with furosemide dramatically increases ototoxicity risk 5, 4