When should metabolic acidosis be treated in chronic kidney disease (CKD) based on serum bicarbonate levels and clinical symptoms?

When to Treat Metabolic Acidosis in CKD

Treat metabolic acidosis in CKD when serum bicarbonate falls below 22 mmol/L, with aggressive pharmacological intervention required when bicarbonate drops below 18 mmol/L. 1, 2

Treatment Thresholds Based on Bicarbonate Levels

Bicarbonate ≥22 mmol/L

• Monitor serum bicarbonate at least every 3 months without pharmacological intervention 1, 2
• Continue routine CKD management and dietary counseling 1

Bicarbonate 18-22 mmol/L

• Consider oral alkali supplementation (sodium bicarbonate 0.5-1.0 mEq/kg/day divided into 2-3 doses) to maintain bicarbonate ≥22 mmol/L 1, 2, 3
• Increase fruit and vegetable intake as first-line or adjunctive therapy, which provides potassium citrate salts that generate alkali and may reduce systolic blood pressure and body weight 2, 3
• Monitor bicarbonate monthly until stable at ≥22 mmol/L, then every 3-4 months 2, 4

Bicarbonate <18 mmol/L

• Initiate pharmacological treatment immediately with oral sodium bicarbonate 1, 2
• Start with 2-4 g/day (25-50 mEq/day) divided into 2-3 doses 2
• This threshold indicates metabolic acidosis requiring intervention to prevent clinical complications 2
• Consider hospitalization if bicarbonate <18 mmol/L with acute illness, catabolic state, symptomatic complications (severe muscle weakness, altered mental status, inability to maintain oral intake), or severe electrolyte disturbances 2

Clinical Rationale for Treatment

The KDIGO guidelines recommend maintaining bicarbonate ≥22 mmol/L because untreated metabolic acidosis causes multiple adverse outcomes 1:

• Protein catabolism and muscle wasting: Acidosis increases oxidation of branched-chain amino acids, leading to malnutrition 2, 5
• Bone demineralization: Chronic acidosis alters calcium-PTH-vitamin D homeostasis, causing bone dissolution and renal osteodystrophy 2, 6, 5
• CKD progression: Treatment to increase bicarbonate by 4-6.8 mEq/L reduces eGFR decline by approximately 4 ml/min/1.73 m² over 6-24 months 7
• Growth retardation in children: Normalization of bicarbonate is critical for return of normal growth parameters 2, 6

Monitoring During Treatment

After initiating alkali therapy, monitor the following parameters 2, 4:

• Serum bicarbonate monthly until stable at ≥22 mmol/L, then every 3-4 months 2
• Blood pressure and weight at each visit to detect sodium retention from sodium bicarbonate 2, 4
• Serum potassium regularly, as alkalinization drives potassium intracellularly 2
• Bone health parameters (calcium, phosphorus, PTH) as acidosis correction improves bone metabolism 4, 6

Treatment Goals and Target Range

The target is to maintain serum bicarbonate ≥22 mmol/L but not exceeding the normal range (22-26 mmol/L). 1, 2 While some observational data suggest targeting bicarbonate near 28 mEq/L may improve outcomes, values >26 mEq/L have been associated with incident heart failure and mortality in the CRIC Study 3. Therefore, aim for 22-26 mmol/L to balance benefits against potential risks 2, 3.

Special Considerations and Pitfalls

Dietary Approach

• Increasing fruit and vegetable intake provides additional benefits beyond bicarbonate supplementation alone, including reduced systolic blood pressure, potential weight loss, and increased fiber intake 2, 3
• Western diets high in animal protein and low in fruits/vegetables create acid accumulation that worsens CKD-related acidosis 2

Contraindications and Cautions

• Avoid citrate-containing alkali in CKD patients exposed to aluminum salts (e.g., aluminum-containing phosphate binders), as citrate increases aluminum absorption and worsens bone disease 2, 6
• Use sodium bicarbonate cautiously in patients with advanced heart failure with volume overload, severe uncontrolled hypertension, or significant edema 2
• Monitor for potential vascular calcification with aggressive alkali therapy 3

Pediatric Considerations

• Pediatric clinicians may treat milder acidosis (bicarbonate >18 mmol/L) more aggressively to optimize growth and bone health, as chronic metabolic acidosis causes growth retardation in children 2, 6

Hospitalized CKD Patients

• CKD patients on chronic low-protein diets should not continue dietary protein restriction during hospitalization for acute illness; the catabolic state requires 1.2-1.5 g/kg/day protein 2, 4
• Protein restriction during acute illness worsens nitrogen balance without preventing dialysis 2, 4

Algorithm Summary

1. Measure serum bicarbonate in all CKD patients stages 3-5 at least every 3 months 1, 2, 6
2. If bicarbonate ≥22 mmol/L: Monitor without intervention 1, 2
3. If bicarbonate 18-22 mmol/L: Consider oral sodium bicarbonate 0.5-1.0 mEq/kg/day plus dietary modification with increased fruits/vegetables 1, 2, 3
4. If bicarbonate <18 mmol/L: Initiate pharmacological treatment with sodium bicarbonate 2-4 g/day (25-50 mEq/day) divided into 2-3 doses 1, 2
5. Target bicarbonate 22-26 mmol/L to prevent complications while avoiding excessive alkalinization 2, 3
6. Monitor monthly until stable, then every 3-4 months, checking blood pressure, weight, potassium, and bone parameters 2, 4