Is Hydrochlorothiazide (HCTZ) an appropriate sole antihypertensive agent for a 73-year-old female with Chronic Kidney Disease (CKD) stage 3 and impaired renal function?

From the Guidelines

Hydrochlorothiazide (HCTZ) is not recommended as the sole antihypertensive agent for a 73-year-old female with Chronic Kidney Disease (CKD) stage 3 and impaired renal function, due to its potential to worsen kidney function and cause electrolyte imbalances.

Recommended Approach

Instead, an ACE inhibitor or angiotensin receptor blocker (ARB) would be a better first-line choice, as they provide kidney protection by reducing proteinuria and slowing CKD progression 1.

• Medications like lisinopril (starting at 5-10 mg daily) or losartan (starting at 25-50 mg daily) are preferred because they not only lower blood pressure but also decrease pressure within the kidneys' filtering units and reduce inflammation.
• If blood pressure remains uncontrolled with an ACE inhibitor or ARB alone, a calcium channel blocker like amlodipine (5-10 mg daily) would typically be added as a second agent rather than HCTZ.

Rationale

The 2021 KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease recommends using ACE inhibitors or ARBs as first-line agents for patients with CKD, due to their renoprotective effects 1.

• HCTZ becomes less effective as kidney function declines and may worsen kidney function, increase uric acid levels, and cause electrolyte imbalances in CKD patients.
• Regular monitoring of kidney function, potassium levels, and blood pressure is essential when starting these medications, with follow-up within 2-4 weeks of initiation.

Key Considerations

• The choice of antihypertensive agent should be individualized based on the patient's specific needs and comorbidities.
• The goal of therapy is to achieve a blood pressure target of <120 mm Hg, as recommended by the KDIGO guideline 1.
• Close monitoring and adjustment of therapy as needed is crucial to optimize outcomes and minimize adverse effects.

From the FDA Drug Label

Hydrochlorothiazide capsules are indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. The use of Hydrochlorothiazide (HCTZ) as a sole antihypertensive agent is indicated, but caution is advised in patients with Chronic Kidney Disease (CKD) stage 3 and impaired renal function. The label does not provide specific guidance for this patient population.

• Key consideration: The patient's impaired renal function may affect the drug's efficacy and safety.
• Clinical decision: It is uncertain whether HCTZ is an appropriate sole antihypertensive agent for this patient, and alternative or additional treatments may be necessary 2.

From the Research

Antihypertensive Therapy for CKD Patients

• The use of Hydrochlorothiazide (HCTZ) as a sole antihypertensive agent for a 73-year-old female with Chronic Kidney Disease (CKD) stage 3 and impaired renal function is a topic of consideration.
• According to 3, a combination of angiotensin II receptor antagonist with calcium channel blocker or diuretic is effective as antihypertensive therapy for patients with CKD.
• However, the study 4 found that addition of diuretics, such as HCTZ, to angiotensin receptor blocker (ARB) was equally effective for the control of hypertension in CKD, but may have a negative effect on renal function.

Efficacy and Safety of HCTZ in CKD Patients

• The study 5 suggests that thiazides, including HCTZ, may be efficacious in reducing blood pressure even in advanced CKD, but close monitoring is necessary due to the risk of electrolyte abnormalities.
• Another study 3 found that a combination of ARB and a controlled-release nifedipine showed a superior antihypertensive effect in CKD patients compared to a fixed-dose combination of losartan and HCTZ.
• The study 4 also found that the percentage changes in urinary excretion of protein to creatinine (UPCR) at 12 months after start of the combination therapy were significantly different in the HCTZ group, indicating a potential benefit of HCTZ in reducing proteinuria.

Blood Pressure Targets for CKD Patients

• The study 6 suggests that a blood pressure target of less than 140/90 mm Hg is reasonable for patients with CKD stage III and IV, and a target systolic BP of 120 to 130 mm Hg and diastolic BP of 70 to 80 mm Hg may yield the greatest benefit while avoiding most of the adverse cardiovascular outcomes associated with lower levels of BP.
• However, the study 7 found that mineralocorticoid receptor antagonists (MRAs) significantly reduced blood pressure in subjects with resistant hypertension associated with stage 3 CKD, but close biochemical monitoring is recommended due to the increased risk of hyperkalemia and worsening of renal function.