What is the association between Acute Kidney Injury (AKI) and metabolic acidosis?

The Association Between Acute Kidney Injury and Metabolic Acidosis

Metabolic acidosis is both a consequence of and a risk factor for acute kidney injury (AKI), creating a bidirectional relationship that can worsen patient outcomes if not properly managed.

Pathophysiological Relationship

How AKI Causes Metabolic Acidosis

When acute kidney injury occurs, several mechanisms lead to metabolic acidosis:

1. Impaired acid excretion:

   • The kidneys lose their ability to excrete hydrogen ions
   • Decreased ammonium production and excretion 1
   • Reduced bicarbonate reabsorption

2. Accumulation of metabolic waste products:

   • Retention of phosphates, sulfates, and organic acids
   • Decreased filtration of acid metabolites 2

3. Electrolyte disturbances:

   • Hyperkalemia often accompanies metabolic acidosis in AKI
   • Hypocalcemia and hyperphosphatemia frequently co-occur 3

How Metabolic Acidosis Contributes to AKI

Recent evidence shows metabolic acidosis can also precipitate or worsen AKI:

• Patients with CKD and metabolic acidosis have a 57-65% higher risk of developing AKI (HR 1.57-1.65) 4
• Acidosis promotes inflammation and oxidative stress in renal tissues
• Acidosis alters renal hemodynamics, potentially reducing perfusion

Clinical Manifestations

The combination of AKI and metabolic acidosis presents with:

• Laboratory findings: decreased serum bicarbonate, increased anion gap
• In COVID-19 patients, proximal tubular injury may manifest as Fanconi syndrome with normal anion gap metabolic acidosis 1
• Respiratory compensation (Kussmaul breathing)
• Altered mental status in severe cases
• Hemodynamic instability in advanced cases

Management Approach

Assessment and Monitoring

• Regular monitoring of acid-base status through arterial blood gases
• Daily monitoring of fluid balance, urine output, and serum creatinine 5
• Measurement of urine electrolytes and calculation of fractional excretion of sodium (FENa) 5

Treatment Strategies

1. Address the underlying AKI:

   • Remove nephrotoxic agents 5
   • Optimize volume status 5
   • Treat underlying causes (infection, sepsis) 5

2. Manage metabolic acidosis:

   • For severe metabolic acidosis (pH ≤7.20) with moderate-to-severe AKI, sodium bicarbonate infusion titrated to maintain pH ≥7.30 may improve survival 6
   • Sodium bicarbonate dosing: Initially 2-5 mEq/kg body weight over 4-8 hours 7
   • Caution against rapid full correction of bicarbonate deficit within 24 hours to avoid rebound alkalosis 7

3. Consider renal replacement therapy when:

   • Conservative management fails 8
   • Severe, refractory acidosis persists
   • Life-threatening electrolyte abnormalities develop
   • Uremic symptoms appear 5

Special Considerations

• Avoid excessive fluid administration in euvolemic or hypervolemic patients 5
• Consider sodium bicarbonate's potential to cause hypernatremia, especially with rapid infusion 7
• KDIGO guidelines suggest exploring the role of sodium bicarbonate in patients with AKI and metabolic acidosis 1

Prevention and Follow-up

• Regular assessment of kidney function in high-risk patients 5
• Serial measurements of serum creatinine and proteinuria after AKI episodes 5
• Monitor patients for 3 months after AKI for resolution or progression to chronic kidney disease 1
• Manage patients with persistent kidney dysfunction according to KDOQI CKD guidelines 1

Conclusion

The relationship between AKI and metabolic acidosis creates a potentially dangerous cycle that requires prompt recognition and management. Addressing both conditions simultaneously is essential for improving outcomes and preventing further kidney damage.