What is the recommended antihypertensive medication for a patient with chronic kidney disease (CKD) and hypertension?

Antihypertensive Treatment for Chronic Kidney Disease

ACE inhibitors are the preferred first-line antihypertensive medication for patients with CKD and hypertension, with a blood pressure target of less than 130/80 mmHg. 1, 2

Blood Pressure Targets

• Target BP should be <130/80 mmHg for all adults with CKD and hypertension. 3, 1, 2
• For patients with moderate-to-severe CKD (eGFR >30 mL/min/1.73 m²), aim for systolic BP of 120-129 mmHg if tolerated, as this provides additional cardiovascular and renal protection. 1
• These targets are more aggressive than older recommendations of <140/90 mmHg, reflecting evidence from trials like SPRINT showing benefit from tighter control. 3

First-Line Medication Selection

ACE inhibitors are the preferred first-line agent for all CKD patients with hypertension, regardless of albuminuria status. 3, 1

Specific Indications by CKD Stage and Albuminuria:

• CKD stage 3 or higher (eGFR <60 mL/min/1.73 m²): ACE inhibitors are strongly recommended regardless of albuminuria level. 3, 1
• CKD stage 1-2 with albuminuria ≥300 mg/g creatinine: ACE inhibitors reduce progression to ESRD and are the preferred agent. 3, 1
• CKD with albuminuria 30-299 mg/g creatinine: ACE inhibitors reduce progression to more advanced albuminuria and cardiovascular events. 3

ARBs as Alternative:

• If ACE inhibitors are not tolerated, ARBs may be used as an alternative. 3, 1, 2
• ACE inhibitors and ARBs are considered to have similar benefits and risks. 3
• ARBs are particularly useful in Black patients who may have smaller responses to ACE inhibitor monotherapy. 4, 5

Dosing Strategy:

• Administer ACE inhibitors or ARBs at the highest approved dose that is tolerated to achieve maximum renoprotective benefits. 1

Monitoring After Initiation

Check blood pressure, serum creatinine, and serum potassium within 2-4 weeks of starting or increasing the dose of an ACE inhibitor or ARB. 1

• Continue the ACE inhibitor or ARB unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase. 3, 1
• An increase in serum creatinine up to 30% is expected due to reduction in intraglomerular pressure and is not a reason to discontinue therapy. 3

Add-On Therapy When BP Goal Not Achieved

Most CKD patients require multiple antihypertensive medications to achieve target BP. 6

Second-Line Therapy:

• Add either a long-acting dihydropyridine calcium channel blocker OR a thiazide-type diuretic. 1
• Concomitant administration of ACE inhibitors with hydrochlorothiazide further reduces blood pressure and eliminates racial differences in response. 4

Third-Line Therapy:

• Add the other class not yet used (CCB or diuretic). 1

Special Population Considerations

Black Patients:

• Initial therapy should include a thiazide-type diuretic or calcium channel blocker, either alone or in combination with an ACE inhibitor/ARB. 1
• Black patients typically have a smaller response to ACE inhibitor or ARB monotherapy due to low-renin hypertension. 4, 5

Kidney Transplant Recipients:

• Use a dihydropyridine calcium channel blocker as first-line therapy, as this improves GFR and kidney survival in transplant patients. 1, 2

Elderly Patients (>80 years):

• Apply the same BP targets and medication choices as younger patients, provided treatment is well tolerated. 1
• Evidence from SPRINT showed that frail elderly patients with CKD sustained benefit from lower BP targets. 3

Diabetic Patients:

• ACE inhibitors or ARBs are the preferred first-line agent for diabetic patients with hypertension, eGFR <60 mL/min/1.73 m², and UACR ≥300 mg/g creatinine. 3
• Blood pressure target of <130/80 mmHg is recommended to reduce CVD mortality and slow CKD progression. 3

Critical Contraindications and Precautions

Absolute Contraindications:

• Never combine an ACE inhibitor, ARB, and direct renin inhibitor together in CKD patients—this increases adverse events (hyperkalemia and acute kidney injury) without additional benefit. 3, 1, 2
• ACE inhibitors and ARBs are absolutely contraindicated during pregnancy. 1

Use with Caution:

• Use caution with ACE inhibitors/ARBs in patients with peripheral vascular disease due to association with renovascular disease. 1
• Further GFR decline beyond the expected 30% increase in creatinine should be investigated for volume contraction, nephrotoxic agents, or renovascular disease. 3

Managing Hyperkalemia

• Hyperkalemia associated with ACE inhibitor/ARB use can often be managed with measures to reduce serum potassium rather than stopping the renin-angiotensin system blocker. 1
• Approximately 15% of patients treated with ACE inhibitors alone experience serum potassium increases greater than 0.5 mEq/L. 4

Common Pitfalls to Avoid

Diuretic Dosing Errors:

• Inadequate diuretic dosing leads to fluid retention and poor BP control, while excessive dosing causes volume contraction, hypotension, and worsening renal function. 3, 1, 2
• Appropriate use of diuretics is crucial to the success of other antihypertensive drugs in CKD. 3

Premature Discontinuation:

• Do not discontinue antihypertensive medications simply because BP falls below target if the patient tolerates the regimen without adverse effects—continue the effective therapy. 1

Lack of Aggressive Treatment:

• Attainment of BP goals needs to be aggressively pursued with multidrug antihypertensive regimens if needed. 7
• Most CKD patients will require more than one drug to achieve blood pressure goals. 8

Medications Without Proven Benefit:

• ACE inhibitors or ARBs are not recommended for patients without hypertension to prevent the development of CKD, as clinical trials have not demonstrated benefit in this setting. 3