What causes renal loss of bicarbonate (HCO3-)?

From the Guidelines

Renal loss of bicarbonate is primarily caused by proximal renal tubular acidosis (Type 2 RTA), distal renal tubular acidosis (Type 1 RTA), and certain medications or conditions that impair the kidney's ability to reabsorb bicarbonate. The most recent and highest quality study, 1, suggests that in people with CKD and serum bicarbonate concentrations <22 mmol/l, treatment with oral bicarbonate supplementation be given to maintain serum bicarbonate within the normal range, unless contraindicated.

Causes of Renal Loss of Bicarbonate

• Proximal renal tubular acidosis (Type 2 RTA): defect in the proximal tubule's ability to reabsorb filtered bicarbonate, leading to excessive bicarbonate excretion in urine
• Distal renal tubular acidosis (Type 1 RTA): impaired hydrogen ion secretion in the distal tubule, resulting in inability to regenerate bicarbonate
• Medications: carbonic anhydrase inhibitors (acetazolamide, topiramate), certain antibiotics, and loop diuretics
• Other causes: hyperparathyroidism, vitamin D deficiency, and kidney transplant rejection The underlying mechanism involves disruption of normal acid-base regulation in the kidneys, where typically 85-90% of filtered bicarbonate is reabsorbed in the proximal tubule and the remainder in the distal nephron, as noted in 1. When these processes are impaired, bicarbonate is excreted in the urine, leading to metabolic acidosis.

Management of Renal Loss of Bicarbonate

• Oral bicarbonate supplementation to maintain serum bicarbonate within the normal range, unless contraindicated, as suggested by 1 and 1
• Higher concentrations of bicarbonate in hemodialysate (38 mmol/L) have been shown to safely increase predialysis serum bicarbonate concentrations, as noted in 1
• An oral dose of sodium bicarbonate, usually about 2 to 4 g/d or 25 to 50 mEq/d, can be used to effectively increase serum bicarbonate concentrations, as noted in 1

From the FDA Drug Label

The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. The cause of renal loss of bicarb is the inhibition of carbonic anhydrase in the kidney by acetazolamide, which affects the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid, resulting in the renal loss of HCO3 ion 2.

• Key points:
  • Carbonic anhydrase inhibition leads to renal loss of bicarb
  • Renal loss of HCO3 ion occurs due to the diuretic effect of acetazolamide
  • This results in the loss of sodium, water, and potassium along with the HCO3 ion 2

From the Research

Causes of Renal Loss of Bicarbonate

• Renal loss of bicarbonate can occur due to various factors, including the use of certain medications such as acetazolamide, which inhibits carbonic anhydrase and leads to increased excretion of bicarbonate in the urine 3, 4.
• In chronic kidney disease (CKD), the kidneys' ability to reabsorb bicarbonate is impaired, leading to acid retention and metabolic acidosis 5.
• The proximal renal tubule is the major site for bicarbonate reabsorption, and any damage or dysfunction in this area can lead to renal loss of bicarbonate 6.
• Other factors that can contribute to renal loss of bicarbonate include dietary acid load, reduced kidney function, and certain genetic disorders 5, 6.

Mechanisms of Bicarbonate Reabsorption

• Bicarbonate reabsorption in the proximal tubule involves the coordinated operation of machineries on both the apical and basolateral membranes of the epithelial cells 6.
• The transepithelial movement of bicarbonate involves the Na+-H+ exchanger NHE3 and the vacuolar H+-ATPase on the apical membrane, and the Na+-HCO3- cotransporter NBCe1 on the basolateral membrane 6.
• Acetazolamide inhibits the activity of carbonic anhydrase, which is necessary for bicarbonate reabsorption, leading to increased excretion of bicarbonate in the urine 4.

Clinical Implications

• Renal loss of bicarbonate can lead to metabolic acidosis, which can have serious clinical implications, including increased morbidity and mortality 5, 7.
• Treatment of metabolic acidosis may involve bicarbonate supplementation, which should be adjusted to maintain a bicarbonate level of <26 mEq/L to avoid overtreatment 5.
• Understanding the mechanisms of bicarbonate reabsorption and the causes of renal loss of bicarbonate is essential for the development of effective treatments for metabolic acidosis and other acid-base disorders 6, 7.