How do you differentiate and treat types of Acute Kidney Injury (AKI)?

Differentiating and Treating Types of Acute Kidney Injury (AKI)

The differentiation of AKI types requires systematic evaluation of prerenal, intrinsic renal, and postrenal causes, with treatment tailored to the underlying etiology to optimize outcomes related to morbidity, mortality, and quality of life. 1

Definition and Classification of AKI

• AKI is diagnosed when serum creatinine increases by ≥0.3 mg/dL within 48 hours or by ≥50% from baseline within 7 days, or when urine output is reduced below 0.5 mL/kg/h for >6 hours 1
• The Kidney Disease Improving Global Outcomes (KDIGO) classification stages AKI based on severity:
  • Stage 1: Increase in serum creatinine 1.5-2.0 times baseline or ≥0.3 mg/dL within 48 hours
  • Stage 2: Increase in serum creatinine 2.0-3.0 times baseline
  • Stage 3: Increase in serum creatinine >3.0 times baseline or serum creatinine ≥4.0 mg/dL with an acute increase of ≥0.5 mg/dL
  • Stage 4 (in some classifications): AKI requiring renal replacement therapy 1

Types of AKI and Differentiation

1. Prerenal AKI

• Characteristics: Results from decreased renal perfusion without structural damage to the kidneys 1
• Diagnostic findings:
  • Fractional excretion of sodium (FENa) <1%
  • Urine sodium <20 mEq/L
  • Urine osmolality >500 mOsm/kg
  • Bland urine sediment
  • Normal renal ultrasound 1
• Common causes: Hypovolemia, heart failure, liver failure, medications affecting renal hemodynamics 1

2. Intrinsic Renal AKI

• Characteristics: Direct damage to kidney structures (tubules, glomeruli, interstitium, or vessels) 1, 2
• Diagnostic findings:
  • FENa >2%
  • Urine sodium >40 mEq/L
  • Abnormal urine sediment (muddy brown casts in ATN, RBC casts in glomerulonephritis)
  • Proteinuria (>500 mg/day) or hematuria (>50 RBCs per high power field) 1
• Common causes:
  • Acute tubular necrosis (ATN) from ischemia or nephrotoxins
  • Acute interstitial nephritis
  • Glomerulonephritis
  • Vascular disorders 2

3. Postrenal AKI

• Characteristics: Obstruction to urinary flow 1
• Diagnostic findings:
  • Hydronephrosis on renal ultrasound
  • Post-obstructive diuresis after relief
  • Variable urine findings 1, 3
• Common causes: Prostatic hypertrophy, nephrolithiasis, tumors, retroperitoneal fibrosis 3

Special Considerations: Hepatorenal Syndrome (HRS-AKI)

• Diagnostic criteria for HRS-AKI in cirrhosis:
  • Diagnosis of cirrhosis and ascites
  • AKI according to ICA-AKI criteria
  • No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg)
  • Absence of shock
  • No current/recent use of nephrotoxic drugs
  • No macroscopic signs of structural kidney injury 1

Diagnostic Approach

1. Initial evaluation:

   • Review medication history for nephrotoxins (NSAIDs, aminoglycosides, contrast media) 1
   • Assess volume status through physical examination 1
   • Obtain basic laboratory tests: serum creatinine, BUN, electrolytes, complete blood count, urinalysis 3

2. Specialized testing:

   • Urine microscopy to identify casts, cells, crystals 1
   • Urine electrolytes and osmolality 3
   • Renal ultrasound to rule out obstruction 1
   • Consider novel biomarkers like NGAL (neutrophil gelatinase-associated lipocalin) to distinguish ATN from HRS in cirrhotic patients 1

Treatment Strategies

General Management for All AKI Types

• Discontinue nephrotoxic medications 1
• Ensure adequate hydration based on volume status assessment 1
• Adjust medication dosages according to reduced renal function 4
• Monitor fluid status, electrolytes, and acid-base balance 1

Specific Management by AKI Type

1. Prerenal AKI:

   • Volume expansion with isotonic crystalloids or albumin in specific cases 1
   • In cirrhotic patients with AKI, administer albumin 1 g/kg/day (maximum 100g) for 2 days 1
   • Treat underlying cause (heart failure, sepsis, etc.) 4

2. Intrinsic Renal AKI:

   • Remove offending agent in nephrotoxic injury 3
   • Provide supportive care while kidney recovers 5
   • Consider corticosteroids for acute interstitial nephritis 2
   • Specific immunosuppressive therapy for glomerulonephritis based on type 2

3. Postrenal AKI:

   • Relieve obstruction (catheterization, nephrostomy, stent placement) 3
   • Treat underlying cause (e.g., prostatic hypertrophy, stones) 3

4. HRS-AKI in Cirrhosis:

   • Hold diuretics and beta-blockers 1
   • Administer albumin 1 g/kg on day 1, then 20-40 g daily 1
   • Add vasoconstrictor therapy:
     • Terlipressin: Start at 1 mg every 4-6 hours, increase to maximum 2 mg every 4-6 hours if no response by day 3 1
     • If terlipressin unavailable: octreotide plus midodrine, or norepinephrine 1
   • Continue therapy until serum creatinine returns to within 0.3 mg/dL of baseline or for 14 days 1

Renal Replacement Therapy (RRT)

• Indications for RRT:
  • Refractory hyperkalemia
  • Volume overload unresponsive to diuretics
  • Severe metabolic acidosis
  • Uremic complications (encephalopathy, pericarditis)
  • Certain toxin removals 5, 4

Follow-up and Monitoring

• AKI increases risk for chronic kidney disease, cardiovascular disease, and mortality 6, 4
• Follow patients after AKI episode with regular monitoring of kidney function 1
• Avoid future nephrotoxic exposures 1, 4
• Consider nephrology referral for:
  • Stage 3 or higher AKI
  • No clear cause identified
  • Inadequate response to supportive care
  • Need for RRT 4

Common Pitfalls to Avoid

• Overreliance on the traditional prerenal/intrarenal/postrenal classification, as many cases of AKI are multifactorial 1
• Indiscriminate fluid administration without proper assessment of volume status 1
• Delayed recognition of HRS-AKI in cirrhotic patients, which requires specific management 1
• Failure to discontinue nephrotoxic medications promptly 1, 4
• Inadequate follow-up after AKI episode, which can lead to missed opportunities for CKD prevention 1, 4