What lowers bicarbonate levels?

What Lowers Bicarbonate Levels?

Bicarbonate levels are lowered by renal loss of HCO3- (primarily through carbonic anhydrase inhibitors like acetazolamide), metabolic acidosis from various causes, and inadequate bicarbonate replacement in dialysis patients.

Pharmacologic Causes

Carbonic Anhydrase Inhibitors

• Acetazolamide directly lowers bicarbonate by inhibiting carbonic anhydrase in the kidney, resulting in renal loss of HCO3- ion which carries out sodium, water, and potassium 1
• This mechanism causes alkalinization of urine and promotion of diuresis through the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid 1
• Dosing ranges from 250 mg to 1 g per 24 hours for various indications, with the diuretic effect specifically targeting bicarbonate excretion 1

Pathophysiologic Causes

Chronic Kidney Disease

• CKD commonly causes metabolic acidosis manifested by low serum bicarbonate, with levels <22 mmol/L associated with increased mortality, CKD progression, and end-stage kidney disease 2, 3, 4, 5
• The mechanism involves impaired renal acid excretion and reduced bicarbonate regeneration as GFR declines 2
• Bicarbonate levels <22 mmol/L in CKD patients show a U-shaped mortality curve, with the lowest mortality observed at bicarbonate levels of 26-29 mmol/L 4

Dialysis-Related Factors

• Inadequate dialysate bicarbonate prescription leaves many patients acidotic before dialysis sessions, with only 67.9% of patients achieving target pre-dialysis bicarbonate ranges without individualized adjustment 6
• Standard "one-size-fits-all" dialysate bicarbonate approaches fail to account for individual patient variation in acid production and bicarbonate needs 6
• Removal of bicarbonate during dialysis without adequate replacement through dialysate contributes to persistent acidosis 2

Metabolic Acidosis from Tissue Hypoperfusion

• Lactic acidosis from tissue hypoperfusion consumes bicarbonate as a buffer, lowering serum levels 7
• However, the underlying cause (shock, sepsis, cardiac failure) rather than bicarbonate depletion itself is the primary driver 7

Clinical Consequences of Low Bicarbonate

Nutritional and Metabolic Effects

• Low bicarbonate increases oxidation of branched chain amino acids (valine, leucine, isoleucine), increases protein degradation, and decreases albumin synthesis 2
• Acidemia causes increased cellular efflux and decreased cellular influx of branched chain amino acids 2
• Plasma branched chain amino acid levels correlate directly with plasma bicarbonate levels in dialysis patients 2

Mortality and Morbidity

• Bicarbonate <22 mmol/L is associated with a 33% increased risk of all-cause mortality in non-dialysis CKD patients (HR 1.33,95% CI 1.05-1.69) 4
• Low bicarbonate at hospital admission independently predicts both acute kidney injury development (8.0% vs 4.1% in normal bicarbonate) and 90-day mortality 8
• Pre-existing low bicarbonate combined with subsequent AKI increases in-hospital mortality by 15-fold compared to normal bicarbonate without AKI 8

Bone Health

• Chronic acidosis causes bone dissolution as bone buffers excess acid, though the relationship between bicarbonate supplementation type and bone protection remains complex 9

Important Clinical Pitfalls

• Do not assume all low bicarbonate requires immediate correction—bicarbonate <27 mmol/L has 99% negative predictive value for obesity hypoventilation syndrome, making it useful for ruling out this diagnosis 2
• In maintenance dialysis, bicarbonate should be monitored monthly and maintained ≥22 mmol/L to prevent adverse outcomes 2, 3
• The association between low bicarbonate and mortality is more pronounced in patients with better nutritional status and lower inflammation, suggesting acidosis itself (not just as a marker of illness) drives outcomes 4