Metabolic acidosis frequently occurs in patients with CKD due to defective acid excretion (resulting in reduced bicarbonate generation), most commonly due to impaired ammoniagenesis. Untreated metabolic acidosis can lead to muscle loss (due to increased muscle proteolysis) and bone loss (due to increased bone resorption and impaired bone formation). In early CKD, metabolic acidosis is typically a normal anion gap hyperchloremic metabolic acidosis. As eGFR declines, organic and inorganic anions are retained, and an increased anion gap metabolic acidosis develops.
Large observational studies have shown a strong association between lower serum bicarbonate levels and both increased progression of CKD and mortality. Alkali therapy, most commonly sodium bicarbonate or sodium citrate, can delay the progression of CKD. Therefore, KDIGO guidelines recommend starting alkali therapy when the serum bicarbonate is chronically <22 mEq/L (22 mmol/L). The alkali salt therapy dose should be titrated to achieve a serum bicarbonate level within the normal range; excessive alkali therapy in the setting of a reduced eGFR may induce a metabolic alkalosis, which is associated with increased mortality. Despite the administration of excess sodium, alkali salts are not associated with volume expansion, even among patients with chronic heart failure or overt edema, most likely because the accompanying anion is not chloride.