What is the best approach to manage hypertension in an elderly patient with chronic kidney disease (CKD)?

Management of Hypertension in Elderly Patients with CKD

Blood Pressure Target

Target a systolic blood pressure of 130-139 mmHg in elderly patients with CKD, prioritizing tolerability and monitoring for orthostatic hypotension, symptomatic hypotension, and electrolyte disturbances. 1, 2

• The 2024 ESC guidelines recommend lowering systolic BP to 130-139 mmHg in patients with diabetic or non-diabetic CKD, with individualized treatment based on tolerability and impact on renal function and electrolytes 1
• For elderly patients (≥65 years) with CKD and moderate-to-severe disease (eGFR >30 mL/min/1.73 m²), a more intensive target of 120-129 mmHg may be considered if well-tolerated 1
• The 2019 KDOQI commentary supports an SBP target <130 mmHg for noninstitutionalized ambulatory community-dwelling adults ≥65 years, but emphasizes that clinical judgment and team-based assessment are reasonable for elderly patients with high comorbidity burden 1
• Avoid reducing diastolic BP below 80 mmHg, as excessive diastolic lowering can increase cardiovascular risk 1

First-Line Medication Selection

Initiate an ACE inhibitor (lisinopril 5 mg daily) or ARB (losartan 25 mg daily) as first-line therapy if albuminuria ≥300 mg/24 hours is present, starting at low doses in elderly patients. 1, 2, 3

• RAS blockers (ACE inhibitors or ARBs) are more effective at reducing albuminuria than other antihypertensive agents and are recommended as part of the treatment strategy in hypertensive patients with microalbuminuria or proteinuria 1
• The KDIGO guideline strongly recommends ACE inhibitors or ARBs in the setting of severely increased urine albumin excretion 1
• Start with lisinopril 5 mg daily or losartan 25 mg daily in elderly patients with CKD to minimize risk of hyperkalemia and acute kidney injury 2

If albuminuria is absent or <300 mg/24 hours, initiate chlorthalidone 12.5 mg daily as first-line therapy, which has robust mortality benefit in elderly patients. 2

• For elderly patients without significant proteinuria, thiazide-type diuretics or calcium channel blockers are appropriate first-line options 1
• Chlorthalidone specifically demonstrates mortality benefit and is effective even in advanced CKD 2

Second-Line and Combination Therapy

Add amlodipine 2.5-5 mg daily or chlorthalidone 12.5 mg daily as second-line therapy when BP remains uncontrolled on monotherapy. 2, 3

• Long-acting dihydropyridine calcium channel blockers (amlodipine) or thiazide-type diuretics are recommended as add-on therapy when BP goals are not achieved 1, 4
• Use a gradual, stepped-care approach rather than aggressive dual therapy initiation in elderly patients with SBP ≥150 mmHg to minimize adverse events 2
• If the patient is on an ACE inhibitor or ARB for albuminuria, add amlodipine as the preferred second agent 3
• If starting with a diuretic, add amlodipine or an ACE inhibitor/ARB depending on albuminuria status 3

Never combine an ACE inhibitor with an ARB, as dual RAS blockade increases risks of hypotension, hyperkalemia, and acute kidney injury without additional benefit. 5, 6

• The VA NEPHRON-D trial demonstrated that combining losartan with lisinopril provided no additional benefit but increased incidence of hyperkalemia and acute kidney injury 5
• FDA labeling for both lisinopril and losartan explicitly warns against dual RAS blockade 5, 6

Critical Monitoring Requirements

Check serum creatinine, eGFR, and potassium within 2-4 weeks after initiating or titrating any antihypertensive medication. 2, 4

• Monitor electrolytes, particularly sodium levels weekly for the first month if adding a thiazide diuretic 2
• Check potassium levels every 2-4 weeks initially when using ACE inhibitors or ARBs 2
• An initial small decline in GFR (10-20%) after starting RAS blockade is acceptable and does not require discontinuation unless accompanied by hyperkalemia or excessive decline 3

Screen for orthostatic hypotension by measuring BP in both sitting and standing positions at every visit in elderly patients. 2, 3

• Elderly patients are at high risk for orthostatic hypotension, which increases fall risk and adverse outcomes 2
• Symptomatic orthostatic hypotension may require dose reduction or medication adjustment 3

Special Considerations for Elderly Patients

Monitor closely for adverse effects including hyperkalemia, acute kidney injury, symptomatic hypotension, and peripheral edema (with calcium channel blockers). 2, 3, 5, 6

• Elderly patients have reduced drug clearance and are more susceptible to adverse effects 3
• NSAIDs should be avoided or used cautiously, as they can deteriorate renal function and attenuate antihypertensive effects when combined with ACE inhibitors or ARBs 5, 6
• Peripheral edema occurs more frequently in elderly women taking amlodipine and may require dose reduction or addition of an ACE inhibitor/ARB 3

For frail elderly patients with multiple comorbidities, limited life expectancy, or frequent falls, target the higher end of the BP range (130-139 mmHg systolic) to minimize treatment-related harms. 1, 2

• The SPRINT trial included adults ≥75 years and demonstrated benefits of intensive BP lowering, but frailty status did not modify effects, and the frailest patients had the greatest reduction in cardiovascular events 1
• However, clinical judgment regarding intensity of BP lowering is reasonable for elderly patients with high comorbidity burden and limited life expectancy 1

Treatment Algorithm

1. Measure BP accurately using sitting and standing measurements to assess for orthostatic hypotension 2
2. Assess albuminuria with urine albumin-to-creatinine ratio 2, 4
3. If albuminuria ≥300 mg/24 hours: Start ACE inhibitor (lisinopril 5 mg daily) or ARB (losartan 25 mg daily) 1, 2
4. If albuminuria <300 mg/24 hours: Start chlorthalidone 12.5 mg daily or amlodipine 2.5-5 mg daily 2, 3
5. If BP remains >130/80 mmHg after 4 weeks: Add second agent (amlodipine if on ACE inhibitor/ARB; ACE inhibitor/ARB or amlodipine if on diuretic) 2, 3, 4
6. Monitor labs at 2-4 weeks after any medication change 2, 4
7. If BP remains uncontrolled on 3 agents: Consider adding spironolactone with careful potassium monitoring, or refer to nephrology 4

Common Pitfalls to Avoid

• Do not combine ACE inhibitors with ARBs - this increases harm without benefit 5, 6
• Do not target diastolic BP <80 mmHg - excessive diastolic lowering increases risk 1
• Do not ignore orthostatic hypotension - always measure standing BP in elderly patients 2, 3
• Do not use NSAIDs chronically - they worsen renal function and blunt antihypertensive effects 5, 6
• Do not start multiple agents simultaneously - use gradual titration to minimize adverse events in elderly patients 2