Why does Chronic Kidney Disease (CKD) cause metabolic acidosis?

Mechanisms of Metabolic Acidosis in Chronic Kidney Disease

Chronic Kidney Disease (CKD) causes metabolic acidosis primarily through impaired acid excretion and reduced bicarbonate production, leading to acid accumulation in the body.

Primary Mechanisms of Metabolic Acidosis in CKD

• CKD impairs the kidney's ability to excrete hydrogen ions and synthesize ammonia, which are essential processes for maintaining acid-base balance 1, 2
• As kidney function declines, there is reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production relative to the acids produced by the body 3
• Metabolic acidosis typically develops when glomerular filtration rate significantly decreases, becoming more common and severe in advanced stages of CKD 4

Contributing Dietary Factors

• Western dietary patterns with high animal protein, cereal, and grain consumption combined with low fruit and vegetable intake create an imbalance between nonvolatile acids and available alkali 1
• Animal proteins contain sulfur-containing amino acids (methionine and cysteine) that produce nonvolatile acids during metabolism 1
• Fruits and vegetables provide potassium citrate salts that generate alkali, which helps buffer acids 1
• The difference between nonvolatile acid production and available alkali is called net endogenous acid production, which is highest with Western diets 1

Pathophysiological Effects

• Chronic metabolic acidosis alters the homeostatic relationships between blood ionized calcium, PTH, and 1,25(OH)₂D₃, leading to bone dissolution 1
• Acidosis directly stimulates endothelial cell secretion of endothelin 1, which enhances sodium-hydrogen exchanger 3 activity, increasing luminal hydrogen ion secretion 1
• Acidosis stimulates angiotensin II production through heightened renin-angiotensin system activity 1
• These compensatory mechanisms to increase hydrogen ion secretion may accelerate kidney disease progression 1, 5

Clinical Consequences of Metabolic Acidosis in CKD

• Protein catabolism is increased, leading to muscle wasting and malnutrition 1, 6
• Bone demineralization occurs, contributing to renal osteodystrophy 1, 2
• Metabolic acidosis is associated with faster progression of kidney disease and increased mortality 5, 3
• Growth retardation in children with CKD may occur due to chronic metabolic acidosis 1

Diagnosis and Management

• Serum bicarbonate levels should be measured in all CKD patients stages 3-5 1
• Metabolic acidosis is diagnosed when serum bicarbonate is <22 mmol/L 4, 3
• Treatment is recommended to maintain serum bicarbonate levels ≥22 mmol/L 1
• Treatment options include:
  • Sodium bicarbonate supplementation 1, 3
  • Increased fruit and vegetable intake to reduce dietary acid load 1, 2
  • Limiting intake of acid-producing foods like animal proteins 6

Important Clinical Considerations

• Increasing fruit and vegetable intake not only raises serum bicarbonate but may also decrease systolic blood pressure and body weight compared to sodium bicarbonate supplementation alone 1
• Citrate-containing alkali salts should be avoided in CKD patients exposed to aluminum salts as they may increase aluminum absorption 1
• Treatment of metabolic acidosis has been shown to slow the progression of CKD 5, 6
• Even mild forms of metabolic acidosis are associated with increased morbidity and mortality and should be treated 6