What is the recommended treatment approach for patients with hypertension and chronic kidney disease (CKD)?

Hypertension Management in Chronic Kidney Disease

Blood Pressure Measurement: The Critical Foundation

Accurate blood pressure measurement using standardized protocols is mandatory before any treatment decisions can be made in CKD patients. 1

• Use standardized office BP measurement with proper patient preparation: 5 minutes of quiet rest, back supported, feet flat on floor, arm at heart level 1
• Automated oscillometric devices are preferred over manual measurement for standardized readings 1
• Routine "casual" office BP readings cannot be used to apply the recommended targets—the relationship between routine and standardized BP is highly variable and unpredictable 1
• Complement office readings with out-of-office monitoring (ambulatory BP monitoring or home BP monitoring) to identify white coat hypertension, masked hypertension, and abnormal dipping patterns 1

Common Pitfall: Applying the <120 mmHg target to routine office BP measurements is potentially hazardous and can lead to overtreatment 1

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Blood Pressure Targets

Target systolic BP <120 mmHg using standardized office measurement for adults with CKD, when tolerated. 1

• This is a Grade 2B recommendation based on cardiovascular and mortality benefits demonstrated in trials like SPRINT 1
• For kidney transplant recipients, target remains <130/80 mmHg 1
• For children with CKD, target 24-hour mean arterial pressure ≤50th percentile for age, sex, and height using ambulatory BP monitoring 1

Clinical Exceptions:

• Consider less intensive BP control (<140/80 mmHg) in patients with frailty, high fall risk, very limited life expectancy, or symptomatic postural hypotension 1
• Elderly patients may tolerate slightly higher targets 2

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First-Line Pharmacologic Therapy: RAS Inhibition

Start an ACE inhibitor or ARB as first-line therapy in CKD patients with albuminuria. 1

Specific Recommendations by Albuminuria Level:

Severely Increased Albuminuria (A3, ≥300 mg/g):

• Strong recommendation (1B) to start ACE inhibitor or ARB in both diabetic and non-diabetic patients 1
• Losartan reduces progression to doubling of serum creatinine and end-stage renal disease in type 2 diabetics with proteinuria 3

Moderately Increased Albuminuria (A2, 30-300 mg/g):

• Weaker recommendation (2C) for ACE inhibitor or ARB in non-diabetic patients 1
• Strong recommendation (1B) for ACE inhibitor or ARB in diabetic patients 1

No Significant Albuminuria (A1):

• No specific first-line drug class is mandated; choose based on comorbidities and BP control 4

Dosing Strategy:

• Titrate to the highest approved dose tolerated—proven benefits were achieved using maximal doses in clinical trials 1
• Lisinopril and losartan both inhibit the renin-angiotensin-aldosterone system, reducing vasopressor activity and aldosterone secretion 3, 5

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Monitoring After RAS Inhibitor Initiation

Check BP, serum creatinine, and serum potassium within 2-4 weeks of starting or increasing ACE inhibitor/ARB dose. 1, 6, 2

When to Continue RAS Inhibition:

• Accept serum creatinine increases up to 30% within 4 weeks 1, 6
• Manage hyperkalemia with potassium-lowering measures rather than stopping the RAS inhibitor 1

When to Stop or Reduce RAS Inhibition:

• Serum creatinine rises >30% within 4 weeks 1, 6
• Symptomatic hypotension occurs 1, 6
• Uncontrolled hyperkalemia despite management 1, 6
• eGFR <15 mL/min/1.73 m² with uremic symptoms 6, 2

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Second-Line and Third-Line Therapy

Most CKD patients require 2-3 antihypertensive agents to achieve BP <120 mmHg. 6, 7

Add-On Algorithm:

Second-Line: Long-Acting Dihydropyridine Calcium Channel Blocker

• Add amlodipine or similar agent if BP remains uncontrolled on maximally tolerated RAS inhibitor 6, 2, 7
• Amlodipine produces vasodilation through calcium channel blockade, reducing peripheral vascular resistance 8
• Never use dihydropyridine CCBs as monotherapy in proteinuric CKD—always combine with RAS blockade 7
• For kidney transplant recipients, dihydropyridine CCB or ARB is specifically recommended (1C) 1

Third-Line: Diuretic Therapy

• Add thiazide-like diuretic (e.g., chlorthalidone) if eGFR ≥30 mL/min/1.73 m² 6, 2, 9
• Switch to loop diuretic if eGFR <30 mL/min/1.73 m² 6, 2
• Chlorthalidone is effective even in stage 4 CKD and can mitigate hyperkalemia risk from RAS inhibitors 9

Fourth-Line: Mineralocorticoid Receptor Antagonist

• Add spironolactone for treatment-resistant hypertension 9
• Monitor closely for hyperkalemia, especially with eGFR <45 mL/min/1.73 m² 9
• Consider novel non-steroidal MRAs (e.g., finerenone) for lower hyperkalemia risk 10

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Critical Contraindications

Never combine ACE inhibitor + ARB + direct renin inhibitor in CKD patients (1B recommendation). 1, 2

• Dual or triple RAS blockade increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 1, 2
• Even ACE inhibitor + ARB combinations are not routinely recommended despite proteinuria reduction 1

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Lifestyle Modifications

Sodium Restriction:

• Target sodium intake <2 g/day (<90 mmol/day, <5 g sodium chloride/day) 1
• This is particularly effective when combined with RAS inhibitors 2, 9
• Exception: Avoid sodium restriction in patients with sodium-wasting nephropathy 1

Physical Activity:

• Recommend moderate-intensity physical activity for cumulative 150 minutes per week 1
• Modify based on cardiorespiratory fitness, physical limitations, cognitive function, and fall risk 1

Dietary Considerations:

• DASH diet or potassium-rich salt substitutes may cause hyperkalemia in advanced CKD (eGFR <30) or hyporeninemic hypoaldosteronism 1
• Maintain protein intake at 0.8 g/kg/day in CKD G3-G5; avoid high protein intake >1.3 g/kg/day 1

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Special Populations

Diabetic CKD:

• Intensive glycemic control and lipid management are essential adjuncts to BP control 1, 10
• SGLT2 inhibitors provide cardiovascular and renal protection beyond BP lowering 6, 10
• Multiple medications are typically required: 3+ antihypertensives, 2+ glucose-lowering agents, and lipid-lowering therapy 1

Elderly and Frail Patients:

• Consider higher protein and calorie targets to prevent sarcopenia 1
• Accept less aggressive BP targets (<140/80 mmHg) if symptomatic hypotension or high fall risk 1, 2

Children with CKD:

• Do not restrict protein intake due to growth impairment risk 1
• Monitor BP annually with ambulatory monitoring and every 3-6 months with standardized office BP 1

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Emerging Therapies

Novel agents under investigation for resistant hypertension in CKD include: 9

• Non-steroidal mineralocorticoid receptor antagonists (ocedurenone)
• Dual endothelin receptor antagonists (aprocitentan)
• Aldosterone synthase inhibitors (baxdrostat)
• Endothelin receptor antagonists like atrasentan have shown promise in reducing renal events in diabetic CKD 10