What are the causes and management of acute kidney injury (AKI)?

Causes and Management of Acute Kidney Injury (AKI)

Acute kidney injury is classified into three major categories: prerenal (68% of cases), intrarenal (primarily acute tubular necrosis), and postrenal causes, with management requiring prompt identification of the underlying etiology, removal of nephrotoxic agents, and appropriate fluid management. 1

Causes of AKI

1. Prerenal Causes

• Volume depletion:
  • Hemorrhage, vomiting, diarrhea, excessive diuresis
  • Decreased effective circulating volume (heart failure, cirrhosis)
  • Excessive diuretic use 1

2. Intrarenal/Intrinsic Causes

• Acute tubular necrosis (ATN):

  • Ischemic injury from prolonged prerenal states
  • Nephrotoxic medications and substances 2:
    • NSAIDs
    • Aminoglycosides
    • ACE inhibitors/ARBs
    • Contrast media
    • Chemotherapeutic agents

• Acute interstitial nephritis (AIN):

  • Drug-induced (antibiotics, NSAIDs, proton pump inhibitors)
  • Immune-mediated diseases 2

• Glomerulonephritis:

  • Immune complex diseases
  • ANCA-associated vasculitis
  • Anti-GBM disease 2

3. Postrenal Causes

• Urinary tract obstruction:
  • Prostatic hypertrophy
  • Nephrolithiasis
  • Malignancy
  • Retroperitoneal fibrosis 1

Special Considerations in Cirrhosis

• Hepatorenal syndrome (HRS-AKI): Functional renal failure that persists despite volume repletion
• Precipitating factors: Spontaneous bacterial peritonitis, GI bleeding, excessive diuresis 1

Diagnosis of AKI

Definition (KDIGO Criteria)

• Increase in serum creatinine by ≥0.3 mg/dL within 48 hours, OR
• Increase in serum creatinine to ≥1.5 times baseline within 7 days, OR
• Urine volume <0.5 mL/kg/h for 6 hours 2

Staging

Stage	Serum Creatinine	Urine Output
1	1.5-1.9× baseline or ≥0.3 mg/dL increase	<0.5 mL/kg/h for 6-12h
2	2.0-2.9× baseline	<0.5 mL/kg/h for ≥12h
3	3.0× baseline or increase to ≥4.0 mg/dL or initiation of RRT	<0.3 mL/kg/h for ≥24h or anuria for ≥12h

Diagnostic Approach

1. History and physical examination:

   • Medication review (nephrotoxic drugs)
   • Volume status assessment
   • Symptoms of systemic illness 1

2. Laboratory evaluation:

   • Serum creatinine and BUN
   • Complete blood count
   • Urinalysis with microscopy
   • Urine electrolytes and fractional excretion of sodium (FENa) 1, 2
     • FENa <1%: Prerenal or HRS
     • FENa >2%: Intrinsic renal disease (ATN)

3. Imaging:

   • Renal ultrasonography to rule out obstruction 1

Management of AKI

General Principles

1. Identify and treat the underlying cause
2. Discontinue nephrotoxic medications 1, 2
3. Optimize hemodynamics and volume status:
   • Fluid resuscitation for hypovolemia
   • Target euvolemia, avoiding both hypovolemia and fluid overload 2
4. Correct electrolyte abnormalities
5. Adjust medication dosages for reduced kidney function 2

Specific Management Based on Cause

Prerenal AKI

• Volume replacement with isotonic crystalloids
• For blood loss: Packed red blood cells to maintain hemoglobin 7-9 g/dL 1
• For patients with cirrhosis and tense ascites: Therapeutic paracentesis with albumin infusion 1

Intrinsic Renal AKI

• ATN: Supportive care, avoid further nephrotoxic exposure
• AIN: Discontinue offending agent, consider corticosteroids for persistent cases
• Glomerulonephritis: Specific immunosuppressive regimens based on type 2

Postrenal AKI

• Relief of obstruction (catheterization, nephrostomy, stenting) 2

Management of HRS-AKI in Cirrhosis

1. Initial management:

   • Discontinue diuretics, beta-blockers, and nephrotoxic drugs
   • Screen and treat infections
   • Albumin infusion (1 g/kg up to 100g) for 2 days 1

2. If serum creatinine remains elevated (>2× baseline):

   • Continue albumin (20-40g daily)
   • Add vasoactive agents (terlipressin 1 mg every 4-6 hours, increased to maximum 2 mg if needed)
   • Alternative: octreotide + midodrine or norepinephrine
   • Continue therapy until serum creatinine returns to within 0.3 mg/dL of baseline or for 14 days 1

Indications for Renal Replacement Therapy

• Refractory hyperkalemia
• Volume overload unresponsive to diuretics
• Severe metabolic acidosis
• Uremic complications (encephalopathy, pericarditis, pleuritis)
• Certain toxin removals 2

Prevention of AKI

General Preventive Measures

• Adequate hydration
• Avoidance of nephrotoxic medications when possible
• Monitoring of kidney function in high-risk patients 1, 2

Specific Prevention in Cirrhosis

• Avoid excessive diuresis
• Albumin infusion with therapeutic paracentesis
• Antibiotic prophylaxis for spontaneous bacterial peritonitis
• Avoid NSAIDs, ACE inhibitors, ARBs, and nonselective beta-blockers in decompensated cirrhosis 1

Prevention of Contrast-Induced AKI

• Pre-procedure volume expansion with isotonic crystalloids
• Use lowest possible contrast volume
• Consider alternatives to iodinated contrast when possible 2

Follow-up After AKI

• Follow-up within 1 month of AKI diagnosis
• Serial measurements of serum creatinine and proteinuria
• Monitoring for development of chronic kidney disease
• Cardiovascular risk assessment 2

Pitfalls to Avoid

• Continued nephrotoxin exposure
• Inadequate follow-up after AKI episode
• Delayed recognition of AKI
• Indiscriminate fluid administration leading to fluid overload 2

AKI is a serious condition with significant implications for morbidity, mortality, and progression to chronic kidney disease. Prompt recognition, identification of the underlying cause, and appropriate management are essential for improving outcomes.