What are the recommended antihypertensive (blood pressure lowering) medications for patients with Chronic Kidney Disease (CKD)?

Antihypertensive Management in Chronic Kidney Disease

First-Line Therapy: ACE Inhibitors or ARBs

ACE inhibitors or ARBs are the preferred first-line antihypertensive agents for patients with CKD, particularly those with albuminuria ≥300 mg/g creatinine, regardless of diabetes status. 1

• For patients with CKD (eGFR <60 mL/min/1.73 m²) and severely increased albuminuria (≥300 mg/g creatinine), ACE inhibitors or ARBs are strongly recommended as first-line therapy because they reduce progression to end-stage kidney disease 1
• In patients with moderately increased albuminuria (30-299 mg/g creatinine), ACE inhibitors or ARBs reduce progression to more severe albuminuria and cardiovascular events, though they have not been proven to prevent progression to end-stage kidney disease 1
• ACE inhibitors and ARBs are considered to have similar benefits and risks; if an ACE inhibitor is not tolerated, switch to an ARB 1
• For patients with CKD and no albuminuria, ACE inhibitors or ARBs may still be reasonable treatment options, though the evidence is less robust 1, 2

Blood Pressure Targets

Target blood pressure should be <130/80 mmHg for all adults with CKD and hypertension. 1

• For patients with CKD and albuminuria ≥30 mg/g creatinine, a more intensive target of <130/80 mmHg is recommended to reduce cardiovascular mortality and slow CKD progression 1
• When tolerated, a systolic blood pressure target of <120 mmHg may provide optimal cardiovascular and renal protection 1, 3
• For patients with CKD and albuminuria <30 mg/g creatinine, a target of <140/90 mmHg is acceptable 1

Dosing and Monitoring Protocol

Use the maximum tolerated dose of ACE inhibitors or ARBs to achieve the proven benefits demonstrated in clinical trials. 1, 2

• Check blood pressure, serum creatinine, and serum potassium within 2-4 weeks of initiating or increasing the dose of an ACE inhibitor or ARB 1, 3, 2
• Continue ACE inhibitor or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation or dose increase 1, 2
• Hyperkalemia associated with ACE inhibitor or ARB use can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the medication 1, 2
• Consider reducing the dose or discontinuing ACE inhibitor or ARB in cases of symptomatic hypotension, uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms in advanced kidney failure (eGFR <15 mL/min/1.73 m²) 1, 2

Second-Line and Add-On Therapy

When blood pressure goals are not achieved with ACE inhibitor or ARB monotherapy, add a long-acting dihydropyridine calcium channel blocker or a thiazide-type diuretic. 3, 2

• Long-acting dihydropyridine calcium channel blockers (such as amlodipine) are effective second-line agents that can be safely combined with ACE inhibitors or ARBs 3, 4
• Thiazide-like diuretics (such as chlorthalidone) are effective alternatives, particularly in patients with stage 4 CKD and treatment-resistant hypertension 5
• Dihydropyridine calcium channel blockers should not be used as monotherapy in proteinuric CKD patients but always in combination with a renin-angiotensin system blocker 4
• If triple therapy (ACE inhibitor/ARB + calcium channel blocker + diuretic) fails to achieve blood pressure control, consider adding low-dose spironolactone with close monitoring for hyperkalemia 1, 3, 2

Critical Contraindications and Precautions

Never combine an ACE inhibitor, ARB, and direct renin inhibitor together, as this triple renin-angiotensin system blockade increases adverse events without additional benefit. 1, 2

• Avoid any combination of ACE inhibitor and ARB therapy in patients with CKD, as clinical trials have shown no benefits on cardiovascular or kidney outcomes and higher rates of hyperkalemia and acute kidney injury 1
• ACE inhibitors and ARBs are contraindicated in pregnancy 2
• Use ACE inhibitors and ARBs with caution in patients with peripheral vascular disease due to association with renovascular disease 2

Special Population Considerations

Kidney Transplant Recipients

• Use a dihydropyridine calcium channel blocker or an ARB as first-line antihypertensive therapy in adult kidney transplant recipients 1, 2
• Target blood pressure <130/80 mmHg regardless of albuminuria level 1

Black Patients

• Initial antihypertensive treatment should include a thiazide-type diuretic or calcium channel blocker, either alone or in combination with an ACE inhibitor or ARB 3, 2
• ACE inhibitors and ARBs may be less effective as monotherapy in black patients (typically a low-renin population) 6

Diabetic CKD Patients

• ACE inhibitors or ARBs are strongly recommended for adults with diabetes, CKD, and albuminuria ≥300 mg/g creatinine 1
• For diabetic patients with albuminuria 30-299 mg/g creatinine, ACE inhibitors or ARBs are suggested as first-line therapy 1
• Without kidney disease or albuminuria, ACE inhibitors or ARBs are not superior to other antihypertensive classes and are not recommended solely for CKD prevention 1

Pediatric CKD Patients

• Start blood pressure-lowering treatment when blood pressure is consistently above the 90th percentile for age, sex, and height 1
• Target systolic and diastolic blood pressure ≤50th percentile for age, sex, and height, particularly in children with proteinuria 1
• Use an ACE inhibitor or ARB as first-line therapy for high blood pressure in children with CKD 1

Resistant Hypertension Management

For resistant hypertension despite triple therapy, add low-dose spironolactone (mineralocorticoid receptor antagonist) with close monitoring for hyperkalemia and kidney function. 1, 3, 2

• Mineralocorticoid receptor antagonists are effective for refractory hypertension but may cause hyperkalemia or reversible decline in kidney function, particularly in patients with low eGFR 1, 2
• Chlorthalidone is an effective alternative for patients with stage 4 CKD and treatment-resistant hypertension 5
• Chlorthalidone can mitigate the risk of hyperkalemia to enable concomitant use of spironolactone, but this combination requires careful monitoring of blood pressure and kidney function 5

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors or ARBs prematurely for mild increases in serum creatinine (<30% rise within 4 weeks), as this is an expected hemodynamic effect 1, 2
• Do not use ACE inhibitors or ARBs in patients without hypertension solely to prevent the development of CKD, as clinical trials have not demonstrated benefit in this setting 1
• Do not combine ACE inhibitors with ARBs, as this increases adverse events without improving outcomes 1
• Do not use non-dihydropyridine calcium channel blockers as monotherapy in proteinuric CKD patients 4