In a 72-year-old man with stage 2 chronic kidney disease and a vitamin B12 level of 834 pg/mL, what does an anion gap of 4 mEq/L and a serum bicarbonate (CO₂) of 29 mEq/L indicate?

Low Anion Gap with Mildly Elevated Bicarbonate: Clinical Interpretation

An anion gap of 4 mEq/L is abnormally low and suggests either hypoalbuminemia, laboratory error, or the presence of unmeasured cations (such as from paraproteinemia), while the CO₂ (bicarbonate) of 29 mEq/L represents mild metabolic alkalosis rather than acidosis. 1

Understanding the Low Anion Gap

Normal Reference Values and Clinical Significance

• Modern ion-selective electrode methodology has lowered the normal anion gap range from the traditional 8-16 mEq/L to 3-11 mEq/L (or 5-12 mEq/L in some laboratories), making an anion gap of 4 mEq/L technically within the lower end of normal but warranting investigation. 1, 2

• An anion gap below 3 mEq/L should be considered definitively low and requires immediate evaluation for underlying causes. 1

• Values of 3-4 mEq/L fall in a gray zone where clinical context becomes critical—in this 72-year-old with stage 2 CKD, further workup is justified. 2

Primary Causes to Investigate

Hypoalbuminemia is the most common cause of low anion gap:

• Each 1 g/dL decrease in serum albumin lowers the anion gap by approximately 2.5-3 mEq/L. 1, 3

• Check serum albumin immediately—if albumin is low (e.g., <3.5 g/dL), this explains the reduced anion gap. 3

• Common conditions causing hypoalbuminemia include nephrotic syndrome, liver cirrhosis, malnutrition, and chronic inflammatory states. 2, 3

Paraproteinemia (particularly multiple myeloma):

• IgG multiple myeloma can present with anion gaps as low as 2 mEq/L due to unmeasured cationic immunoglobulins. 2

• Given the patient's age (72 years) and CKD, obtain serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) to exclude monoclonal gammopathy. 1, 2

• This is a critical diagnostic consideration as it represents a potentially life-threatening but treatable condition. 1

Laboratory error:

• A high incidence of anion gap values <2 mEq/L in a laboratory suggests quality control issues with electrolyte measurement. 2

• Verify the result by repeating electrolytes and ensuring proper specimen handling. 2

Interpreting the Elevated Bicarbonate (CO₂ 29 mEq/L)

Clinical Context in CKD

• The bicarbonate of 29 mEq/L represents mild metabolic alkalosis, not acidosis—this is above the normal range of 22-28 mEq/L. 4

• In CKD patients, the K/DOQI guidelines recommend maintaining serum total CO₂ >22 mEq/L to prevent the complications of metabolic acidosis (bone disease, muscle wasting, CKD progression). 4

• However, bicarbonate levels >24 mEq/L may be associated with worsening cardiovascular outcomes in some CKD patients, creating a therapeutic dilemma. 5

Possible Explanations for Mild Alkalosis

Compensatory or iatrogenic alkalosis:

• If the patient is taking oral alkali supplementation (sodium bicarbonate, citrate) for CKD management, this could explain the mildly elevated bicarbonate. 4

• Diuretic use (loop or thiazide diuretics) commonly causes contraction alkalosis in CKD patients. 5

• Volume depletion from any cause can generate metabolic alkalosis through increased proximal tubule bicarbonate reabsorption. 5

Respiratory compensation:

• Chronic respiratory acidosis (from COPD, obesity hypoventilation) triggers renal bicarbonate retention—check arterial blood gas if clinically indicated. 6

Critical Diagnostic Algorithm

Immediate Laboratory Workup

1. Serum albumin – to assess for hypoalbuminemia as the cause of low anion gap 2, 3

2. Repeat basic metabolic panel – to confirm the low anion gap and rule out laboratory error 2

3. Serum protein electrophoresis (SPEP) and immunofixation – to exclude multiple myeloma or other paraproteinemias 1, 2

4. Medication review – identify diuretics, alkali supplements, or other agents affecting acid-base balance 5

5. Arterial blood gas (if indicated) – to determine primary vs. compensatory acid-base disturbance 6

Clinical Pitfalls to Avoid

• Do not assume the low anion gap is benign—it may mask a concurrent high anion gap metabolic acidosis (e.g., if the patient develops lactic acidosis or uremic acidosis, the baseline low gap could normalize rather than elevate, delaying diagnosis). 1

• Do not overlook multiple myeloma—this is a life-threatening diagnosis that presents with low anion gap in approximately 50% of IgG myeloma cases. 1, 2

• Do not use outdated reference ranges—many clinicians still reference the old 8-16 mEq/L range, which would incorrectly classify this patient's anion gap as severely abnormal when it may be near the lower limit of the modern normal range. 1, 2

• Recognize that the mildly elevated bicarbonate is NOT consistent with metabolic acidosis—the patient does not have acidosis despite having CKD, so do not initiate alkali therapy. 4, 5

Management Implications in Stage 2 CKD

• Stage 2 CKD (GFR 60-89 mL/min/1.73m²) typically does not cause metabolic acidosis—acidosis usually develops when GFR falls below 20-25 mL/min/1.73m². 5

• The elevated bicarbonate suggests this patient is not acidotic and does not require alkali supplementation per K/DOQI guidelines, which recommend treatment only when bicarbonate is <22 mEq/L. 4

• If the patient is already receiving alkali therapy, consider reducing or discontinuing it given the elevated bicarbonate and potential cardiovascular risks of bicarbonate >24 mEq/L. 5

• Monitor for progression of CKD and development of true metabolic acidosis as renal function declines, but this is not the current clinical picture. 4, 5