What is the best treatment for hypertension in a patient with chronic kidney disease (CKD)?

Treatment of Hypertension in Chronic Kidney Disease

All patients with CKD and hypertension should receive an ACE inhibitor or ARB as first-line therapy, with a blood pressure goal of less than 130/80 mmHg. 1, 2, 3

Blood Pressure Targets

• Target BP should be <130/80 mmHg for all adults with CKD and hypertension. 1, 2, 3

• For patients with moderate-to-severe CKD (eGFR >30 mL/min/1.73 m²), aim for a systolic BP of 120-129 mmHg if tolerated, as this provides additional cardiovascular and renal protection. 1, 2, 3

• These targets are more aggressive than older JNC-8 guidelines which recommended <140/90 mmHg, reflecting newer evidence showing benefit from tighter control. 4

First-Line Medication Selection

ACE inhibitors are the preferred first-line agent for all CKD patients with hypertension. 1, 2, 3

• ACE inhibitors (or ARBs if ACE inhibitors are not tolerated) are strongly recommended for:

  • CKD stage 3 or higher regardless of albuminuria 1
  • CKD stage 1-2 with any degree of albuminuria 1, 2
  • Severely increased albuminuria (A3) without diabetes 2
  • Moderately-to-severely increased albuminuria (A2 and A3) with diabetes 2

• If an ACE inhibitor causes intolerable side effects (typically cough), switch to an ARB as the alternative. 1, 3

• Administer ACE inhibitors or ARBs at the highest approved dose that is tolerated to achieve maximum renoprotective benefits. 2

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. 2, 3

• Continue the ACE inhibitor or ARB unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase. 2, 3

• A creatinine rise of up to 30% is expected and acceptable, reflecting hemodynamic changes rather than kidney injury. 3

Add-On Therapy When BP Goal Not Achieved

When a single agent does not achieve BP control, add medications in the following sequence:

• Second-line: Add either a long-acting dihydropyridine calcium channel blocker OR a thiazide-type diuretic. 3, 5

• Third-line: Add the other class not yet used (CCB or diuretic). 3

• For resistant hypertension despite three agents, add low-dose spironolactone (mineralocorticoid receptor antagonist) with close monitoring of potassium and renal function. 3, 6

Special Population Considerations

Black Patients with CKD

• Initial therapy should include a thiazide-type diuretic or calcium channel blocker, either alone or in combination with an ACE inhibitor/ARB. 2, 3

• This recommendation differs from non-Black patients due to lower renin profiles and better response to diuretics and CCBs in this population. 4

Kidney Transplant Recipients

• Use a dihydropyridine calcium channel blocker as first-line therapy, as this improves GFR and kidney survival in transplant patients. 1, 3

• ARBs are an acceptable alternative first-line option. 3

Elderly Patients (>80 years)

• Apply the same BP targets and medication choices as younger patients, provided treatment is well tolerated. 3

• Test for orthostatic hypotension before starting or intensifying BP medications. 3

Critical Contraindications and Precautions

• Never combine an ACE inhibitor, ARB, and direct renin inhibitor together in CKD patients—this increases adverse events without additional benefit. 1, 2, 3

• ACE inhibitors and ARBs are absolutely contraindicated during pregnancy. 3

• Use caution with ACE inhibitors/ARBs in patients with peripheral vascular disease due to association with renovascular disease. 3

• Consider reducing or discontinuing ACE inhibitor/ARB in cases of:

  • Symptomatic hypotension 2, 3
  • Uncontrolled hyperkalemia despite medical management 2, 3
  • Advanced kidney failure (eGFR <15 mL/min/1.73 m²) to reduce uremic symptoms 2, 3

Managing Hyperkalemia

• Hyperkalemia associated with ACE inhibitor/ARB use can often be managed with measures to reduce serum potassium (dietary restriction, diuretics, potassium binders) rather than stopping the renin-angiotensin system blocker. 3

• This approach preserves the renoprotective benefits of ACE inhibitors/ARBs while addressing the electrolyte abnormality. 3

Common Pitfalls to Avoid

• Inadequate diuretic dosing leads to fluid retention and poor BP control, while excessive dosing causes volume contraction, hypotension, and worsening renal function. 2, 3

• Do not discontinue antihypertensive medications simply because BP falls below target if the patient tolerates the regimen without adverse effects—continue the effective therapy. 4

• Avoid using dihydropyridine calcium channel blockers as monotherapy in proteinuric CKD patients; always combine with a renin-angiotensin system blocker for optimal renoprotection. 5

• Starting ACE inhibitors/ARBs at full dose in advanced CKD (creatinine >2 mg/dL) increases risk of acute kidney injury—begin with lower doses and titrate gradually with frequent monitoring. 7