Hidden Acid Retention with Normal Serum Bicarbonate Level in Chronic Kidney Disease

Management of metabolic acidosis is crucial for preserving bone, muscle, and renal health, as evidenced by the results of several interventional studies conducted on patients with chronic kidney disease (CKD). Considering the continuity of CKD progression over time, it is reasonable to deduce that a subclinical form of metabolic acidosis may exist prior to the manifestation of overt metabolic acidosis. Covert H⁺ retention with normal serum bicarbonate level in patients with CKD may result in maladaptive responses that contribute to kidney function deterioration, even in the early stages of the disease. The loss of adaptive compensatory mechanisms of urinary acid excretion may be a key factor in this process. Early modulation of these responses could be an important therapeutic strategy in preventing CKD progression. However, to date, the optimal approach for alkali therapy in subclinical metabolic acidosis in CKD remains uncertain. There is a lack of established guidelines on when to initiate alkali therapy, potential side effects of alkali agents, and the optimal blood bicarbonate levels based on evidence-based practices. Therefore, further research is necessary to address these concerns and establish more robust guidelines for the use of alkali therapy in patients with CKD. Herein, we provide an overview of recent developments on this subject and examine the potential therapeutic approaches that interventional treatments may present for patients with hidden H⁺ retention, exhibiting normal serum bicarbonate levels - commonly described as subclinical or eubicarbonatemic metabolic acidosis in patients with CKD.