What are the preferred antihypertensive medications for an adult with chronic kidney disease?

Preferred Antihypertensive Medications for CKD

ACE inhibitors are the first-line preferred antihypertensive medication for adults with chronic kidney disease, with ARBs reserved as an alternative if ACE inhibitors are not tolerated. 1, 2

Blood Pressure Target

• Treat all adults with hypertension and CKD to a BP goal of less than 130/80 mmHg. 1, 2
• 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 based on SPRINT trial data. 3, 2

First-Line Medication: ACE Inhibitors

ACE inhibitors are the preferred first-line agent for all CKD patients with hypertension. 2, 4

Specific Indications for ACE Inhibitors:

• CKD stage 3 or higher (regardless of albuminuria level) 1, 2
• CKD stage 1-2 with albuminuria ≥300 mg/day (or ≥300 mg/g albumin-to-creatinine ratio) 1, 4
• Any CKD stage with moderately-to-severely increased albuminuria and diabetes 4

Dosing Strategy:

• Start with a low dose and titrate up to the highest approved dose that is tolerated to achieve maximum renoprotective benefits. 2, 4

Alternative: ARBs

If an ACE inhibitor is not tolerated, use an ARB as the alternative first-line agent. 1, 2

• ARBs provide similar renoprotection and cardiovascular benefits as ACE inhibitors. 5, 6
• ARBs are better tolerated than ACE inhibitors, making them a practical therapeutic option when side effects (particularly cough) occur. 6

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, 4

• Continue the ACE inhibitor or ARB unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase. 2, 4
• An increase in serum creatinine up to 30% is expected due to reduction in intraglomerular pressure and is acceptable. 1
• Continue ACE inhibitor/ARB even when eGFR falls below 30 mL/min/1.73 m². 4

Add-On Therapy When BP Goal Not Achieved

When BP remains above target despite maximized ACE inhibitor or ARB:

Second-Line Options:

• Add either a long-acting dihydropyridine calcium channel blocker OR a thiazide-type diuretic. 2
• For Black patients with CKD, include a thiazide-type diuretic or calcium channel blocker in the initial regimen. 2

Third-Line:

• Add the other class not yet used (CCB or diuretic). 2

Important Notes on Add-On Therapy:

• Non-dihydropyridine CCBs consistently reduce albuminuria and slow decline in kidney function. 5
• Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. 5
• Diuretics require careful dosing: inadequate dosing leads to fluid retention and poor BP control, while excessive dosing causes volume contraction, hypotension, and worsening renal function. 3, 2

Critical Contraindications

Never combine an ACE inhibitor, ARB, and direct renin inhibitor together in CKD patients—this combination increases adverse events without additional benefit. 3, 2, 4

• Despite older evidence suggesting potential benefit from dual ACE inhibitor/ARB therapy 7, large cardiology trials and diabetic nephropathy trials have demonstrated harms with this combination. 1
• ACE inhibitors and ARBs are absolutely contraindicated during pregnancy. 2

Special Population Considerations

Kidney Transplant Recipients:

• Use a dihydropyridine calcium channel blocker as first-line therapy instead of ACE inhibitors/ARBs, as this improves GFR and kidney survival in transplant patients. 3, 2

Elderly Patients (>80 years):

• Apply the same BP targets and medication choices as younger patients, provided treatment is well tolerated. 2
• The SPRINT trial demonstrated that frail elderly patients with CKD sustained benefit from lower BP targets without increased harm. 1

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors/ARBs for creatinine increases <30% within the first 4 weeks—this is an expected hemodynamic effect. 1, 2, 4
• Investigate further GFR decline beyond 30% for other factors including volume contraction, nephrotoxic agents, or renovascular disease. 1
• Manage hyperkalemia with potassium-lowering measures rather than immediately stopping the RAAS blocker. 2
• Use caution with ACE inhibitors/ARBs in patients with peripheral vascular disease due to association with renovascular disease. 2