What are the recommended antihypertensives (blood pressure medications) for a patient with Chronic Kidney Disease (CKD) stage 3b?

Antihypertensive Management for CKD Stage 3b

For patients with CKD stage 3b, start with an ACE inhibitor (or ARB if ACE inhibitor not tolerated) as first-line therapy, targeting a blood pressure <130/80 mmHg, with consideration for the more intensive target of <120 mmHg systolic when tolerated. 1

Blood Pressure Targets

• Target systolic BP <120 mmHg when tolerated using standardized office BP measurement, which provides optimal cardiovascular and renal protection in CKD patients 1
• The alternative acceptable target is <130/80 mmHg for all adults with CKD and hypertension 1
• These targets are more aggressive than older recommendations and reflect evidence showing benefit from tighter control 2

Critical caveat: The <120 mmHg target applies only to standardized office BP measurements—applying this target to non-standardized measurements is potentially hazardous 1

First-Line Medication Selection

ACE Inhibitors or ARBs as Primary Agents

Start with an ACE inhibitor as the preferred first-line agent for all CKD stage 3b patients with hypertension 3, 2

• ACE inhibitors are strongly recommended regardless of albuminuria status in CKD stage 3 or higher 2
• If ACE inhibitor is not tolerated (e.g., cough, angioedema), switch to an ARB—but wait 6 weeks after discontinuing the ACE inhibitor before starting the ARB if angioedema occurred 1
• Administer at the highest approved dose that is tolerated to achieve maximum renoprotective benefits, as trial benefits were achieved at these doses 1

Specific Indications by Albuminuria Status

• With severely increased albuminuria (A3): ACE inhibitor or ARB is strongly recommended (Class 1B recommendation) 1
• With moderately increased albuminuria (A2): ACE inhibitor or ARB is recommended 1
• Without albuminuria: ACE inhibitor or ARB remains reasonable even in the absence of proteinuria 1, 3

Mandatory Monitoring Protocol

Check BP, serum creatinine, and serum potassium within 2-4 weeks of initiating or increasing the dose of an ACE inhibitor or ARB 1, 3

When to Continue vs. Discontinue

• Continue the ACE inhibitor/ARB if creatinine rises ≤30% within 4 weeks—this modest rise reflects expected hemodynamic changes and does not indicate harm 1, 4
• Consider dose reduction or discontinuation only if:
  • Creatinine rises >30% within 4 weeks 1
  • Symptomatic hypotension occurs 1
  • Uncontrolled hyperkalemia persists despite medical management 1

Managing Hyperkalemia

Hyperkalemia associated with ACE inhibitor/ARB use should be managed with measures to reduce serum potassium rather than automatically stopping the medication 1, 3

• Options include dietary potassium restriction, discontinuing potassium supplements or salt substitutes, adding diuretics, or using potassium binders 1

Add-On Therapy When BP Goal Not Achieved

Second-Line Agent

Add either a long-acting dihydropyridine calcium channel blocker (CCB) OR a thiazide-type diuretic as second-line therapy 3, 2

• Dihydropyridine CCBs (amlodipine, felodipine) are preferred over non-dihydropyridines 1
• Important: Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD but always in combination with a RAS blocker, as they impair renal autoregulation and are less renoprotective unless combined with ACE inhibitor/ARB 5, 6
• For CKD stage 3b (eGFR 30-44 mL/min/1.73 m²), thiazide-type diuretics may still be effective, but loop diuretics become necessary when eGFR <30 mL/min 4, 6

Third-Line Agent

Add the other class not yet used (CCB or diuretic) to achieve triple therapy 2

Resistant Hypertension

For resistant hypertension despite triple therapy, add low-dose spironolactone (mineralocorticoid receptor antagonist) with close monitoring 1, 3

• Spironolactone is effective for refractory hypertension but carries significant risk of hyperkalemia and reversible decline in kidney function, particularly in patients with low eGFR like CKD stage 3b 1, 3
• Monitor potassium and renal function closely, especially if eGFR <45 mL/min 4

Critical Contraindications

Never combine an ACE inhibitor, ARB, and direct renin inhibitor together—this triple RAS blockade increases adverse events without additional benefit 1, 2

• Dual ACE inhibitor + ARB therapy is also not recommended 1
• ACE inhibitors and ARBs are absolutely contraindicated in pregnancy 3, 4
• Use caution in patients with peripheral vascular disease due to association with renovascular disease 3

Special Population Considerations

Black Patients

Initial therapy should include a thiazide-type diuretic or CCB, either alone or in combination with an ACE inhibitor/ARB 3, 4

Elderly Patients

Apply the same BP targets and medication choices as younger patients, provided treatment is well tolerated 2

• Test for orthostatic hypotension before starting or intensifying BP-lowering medication 3
• Less intensive BP-lowering therapy is reasonable in patients with very limited life expectancy or symptomatic postural hypotension 1

Common Pitfalls to Avoid

• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30%—this is expected and acceptable 1, 4
• Avoid NSAIDs, potassium supplements, and potassium-rich salt substitutes while on RAS inhibitors, as these increase hyperkalemia risk 4
• Do not use non-standardized BP measurements to guide intensive BP targets—this can lead to overtreatment 1
• Inadequate diuretic dosing leads to fluid retention and poor BP control, while excessive dosing causes volume contraction and worsening renal function 2

Lifestyle Modifications

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to enhance antihypertensive efficacy 4, 7

• Advise moderate-intensity physical activity for at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance 1