How to manage a 69-year-old female with hyperglycemia and impaired renal function on chlorthalidone?

Management of Chlorthalidone-Induced Metabolic Abnormalities in a 69-Year-Old Female with CKD

Chlorthalidone should be continued with close monitoring of electrolytes, as it remains effective for blood pressure control even in advanced CKD, but requires careful management of metabolic abnormalities.

Laboratory Interpretation

The patient's BMP shows several significant abnormalities:

• Elevated CO2 (bicarbonate) of 33 mmol/L - indicating metabolic alkalosis
• Mildly elevated glucose of 108 mg/dL - suggesting impaired glucose tolerance
• Elevated creatinine of 1.12 mg/dL with reduced eGFR of 53 ml/min - indicating stage 3a CKD
• Elevated BUN of 29 mg/dL - suggesting pre-renal azotemia
• Normal sodium, potassium, anion gap, and calcium

Management Algorithm

1. Diuretic Management

• Continue chlorthalidone but consider dose reduction to 12.5 mg daily 1, 2, 3
• Chlorthalidone remains effective for blood pressure control even in advanced CKD 1, 3
• Monitor electrolytes within 2-4 weeks after any dose adjustment 2

2. Metabolic Alkalosis Management

• Metabolic alkalosis (elevated CO2 of 33) is likely due to chlorthalidone-induced volume contraction and chloride depletion
• Consider adding small doses of potassium chloride supplement if potassium trends downward, even if currently normal 1
• Ensure adequate hydration while maintaining sodium restriction

3. Renal Function Monitoring

• Schedule follow-up BMP in 2-4 weeks to monitor:
  • Creatinine (baseline 1.12 mg/dL)
  • eGFR (baseline 53 ml/min)
  • Electrolytes, especially potassium and bicarbonate
• Temporary increases in creatinine may occur with diuretic therapy but are often hemodynamically mediated and reversible 1

4. Glucose Management

• Monitor fasting glucose levels regularly as thiazide diuretics can worsen glucose control 4
• Consider HbA1c testing to better assess glycemic control
• If glucose levels continue to rise, consider alternative antihypertensive agents 1

Important Considerations

Efficacy in CKD

Recent evidence strongly supports the efficacy of chlorthalidone in advanced CKD. The CLICK trial demonstrated that chlorthalidone 12.5 mg daily reduced 24-hour systolic blood pressure by 10.5 mmHg in patients with stage 4 CKD 3. This challenges the traditional belief that thiazide diuretics lose effectiveness in advanced CKD.

Metabolic Effects to Monitor

1. Metabolic alkalosis: The elevated CO2 of 33 mmol/L indicates metabolic alkalosis, a common complication of thiazide diuretics due to volume contraction and chloride depletion 1

2. Glucose intolerance: The mildly elevated glucose (108 mg/dL) may be related to chlorthalidone. Thiazide diuretics can increase fasting glucose levels by approximately 5-10 mg/dL 4

3. Pre-renal azotemia: The elevated BUN (29 mg/dL) with moderately reduced eGFR suggests volume depletion, which should be addressed with careful fluid management 5

Potential Complications and Cautions

• Hypoglycemia risk: Patients with renal impairment are at increased risk of hypoglycemia due to decreased renal gluconeogenesis and impaired insulin clearance 6
• Electrolyte disturbances: Monitor for hypokalemia, hyponatremia, and hypercalcemia, which can occur with thiazide diuretics 1
• Worsening renal function: Use chlorthalidone with caution in severe renal disease as it may precipitate azotemia 7

Alternative Approaches if Needed

If metabolic abnormalities worsen or blood pressure remains uncontrolled:

1. Consider switching to a loop diuretic if eGFR declines below 30 ml/min 1
2. Consider adding an ACE inhibitor or ARB if proteinuria is present, with careful monitoring of potassium and creatinine 1
3. Consider calcium channel blockers as an alternative if metabolic abnormalities persist 1

The patient should be reassessed within 2-4 weeks with repeat BMP and blood pressure monitoring to ensure metabolic stability while maintaining effective blood pressure control.