A 78-year-old man with long-standing hypertension has been well controlled on hydrochlorothiazide (Microzide) 25 mg daily plus lisinopril. Routine labs now show serum creatinine 2.1 mg/dL with eGFR 28 mL/min/1.73 m² (previously 52). His blood pressure has drifted up to 158/92. Which of the following is the most appropriate adjustment to his diuretic therapy?

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✅ C. Discontinue hydrochlorothiazide and start furosemide (Lasix)
Thiazide diuretics lose natriuretic and antihypertensive efficacy once eGFR falls below roughly 30 mL/min/1.73 m² because they depend on adequate distal tubular delivery. Loop diuretics such as furosemide retain efficacy in advanced CKD because they act on the thick ascending limb and are not dependent on high GFR. Switching to a loop diuretic is the guideline-supported next step for diuretic-responsive hypertension in CKD stage 4.

❌ A. Increase hydrochlorothiazide to 50 mg daily
HCTZ has a flat dose-response for BP above 25 mg, and it is essentially ineffective once eGFR is under 30. Dose escalation in this setting adds metabolic toxicity without BP benefit. This approach would be considered only when eGFR is preserved and the patient is not yet at goal — but 50 mg is still generally discouraged.

❌ B. Add spironolactone (Aldactone) 25 mg daily
Spironolactone can help resistant hypertension, but adding a potassium-sparing diuretic to a patient already on an ACE inhibitor with eGFR 28 creates a high risk of hyperkalemia and is typically contraindicated when eGFR is <30. This would be appropriate only in resistant HTN with preserved renal function and normal potassium.

❌ D. Continue hydrochlorothiazide and add metolazone
Metolazone is sometimes used in combination with a loop diuretic for refractory volume overload in heart failure, but adding a second thiazide-like agent does not solve the core problem — thiazides alone are ineffective at this GFR. This combination is reserved for diuretic resistance in HF, not primary HTN.

:::important
Thiazides fail below eGFR 30. Switch to a loop diuretic for blood pressure control in advanced CKD.
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