What is the recommended approach to managing hypertension in patients with chronic kidney disease?

Management of Hypertension in Chronic Kidney Disease

Target a systolic blood pressure <120 mm Hg using standardized office measurement for most adults with CKD, and initiate an ACE inhibitor or ARB as first-line therapy if albuminuria ≥30 mg/24h is present. 1, 2

Blood Pressure Targets by Patient Characteristics

For Adults <65 Years Without Diabetes

• Target BP <120/80 mm Hg using standardized office measurement to reduce cardiovascular death and stroke, which are the leading causes of mortality in CKD patients 2, 3
• For patients with albuminuria <30 mg/24h, a less stringent target of <140/90 mm Hg is acceptable 1, 4
• For albuminuria 30-300 mg/24h (A2): target <130/80 mm Hg 1, 2
• For albuminuria ≥300 mg/24h (A3): target <130/80 mm Hg 1, 2

For Adults ≥65 Years

• Target systolic BP 130-139 mm Hg rather than aggressive targets below 120 mm Hg, as this range balances cardiovascular protection with safety in older adults 2, 3
• This prevents excessive hypotension risks while still reducing cardiovascular mortality 2

For Patients With Diabetes and CKD

• Albuminuria <30 mg/24h: target <140/90 mm Hg 1
• Albuminuria ≥30 mg/24h: target <130/80 mm Hg 1, 2

For Kidney Transplant Recipients

• Target <130/80 mm Hg using standardized office measurement 1, 3

For Children With CKD

• Target 24-hour mean arterial pressure ≤50th percentile for age, sex, and height using ambulatory blood pressure monitoring 1
• When ABPM unavailable, target office systolic BP <90th percentile for age, sex, and height using standardized auscultatory measurement 1

First-Line Pharmacological Management

ACE Inhibitors or ARBs: The Foundation

• Start ACE inhibitor or ARB for all CKD patients with albuminuria ≥300 mg/24h (A3 category) regardless of diabetes status—this is a strong recommendation (Grade 1B) 1, 2, 3
• For albuminuria 30-300 mg/24h (A2 category): ACE inhibitor or ARB is suggested for non-diabetics (Grade 2C) and recommended for diabetics (Grade 1B) 1
• These agents provide renoprotection beyond BP control by reducing proteinuria and slowing CKD progression 2, 3

Dosing Strategy

• Use the highest approved dose that is tolerated because proven benefits in trials were achieved at these doses 1

For Patients Without Albuminuria

• Standard first-line options include thiazide/thiazide-like diuretics, calcium channel blockers, ACE inhibitors, or ARBs 3

For Kidney Transplant Recipients

• Start with dihydropyridine calcium channel blocker or ARB as first-line (Grade 1C) 1
• Calcium channel blockers improve GFR and kidney survival in transplant patients 3

For Children With CKD

• Use ACE inhibitor or ARB as first-line therapy as these lower proteinuria and are usually well-tolerated 1

Second-Line and Additional Agents

When Target Not Achieved With Monotherapy

• Add a diuretic as second-line therapy 4
• Diuretics augment the antihypertensive and antialbuminuric effects of ACE inhibitors/ARBs 4

For Treatment-Resistant Hypertension

• Add spironolactone to the baseline regimen 5
• However, hyperkalemia risk restricts broad use in moderate-to-advanced CKD 5
• Chlorthalidone is an effective alternative for stage 4 CKD with uncontrolled hypertension, including treatment-resistant cases 5
• Chlorthalidone can mitigate hyperkalemia risk to enable concomitant spironolactone use, but requires careful monitoring 5

Additional Options

• Long-acting dihydropyridine calcium channel blockers are reasonable second- or third-line options 5
• Calcium channel blockers may slow CKD progression when combined with ACE inhibitors 4

Critical Monitoring Parameters

After Initiating or Adjusting ACE Inhibitor/ARB

• Check serum creatinine, eGFR, and potassium within 2-4 weeks of initiation or dose increase 1, 2, 3
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation or dose increase 1, 2
• A creatinine rise up to 30% is acceptable and expected 1

Managing Hyperkalemia

• Hyperkalemia can often be managed with measures to reduce serum potassium rather than decreasing dose or stopping the ACE inhibitor/ARB 1

When to Reduce Dose or Discontinue

• Consider reducing dose or discontinuing in cases of: 1
  • Symptomatic hypotension
  • Uncontrolled hyperkalemia despite medical treatment
  • Need to reduce uremic symptoms while treating kidney failure (eGFR <15 ml/min/1.73 m²)

Postural Hypotension Monitoring

• Check for postural hypotension regularly when treating CKD patients with BP-lowering drugs 1

Essential Lifestyle Modifications

Dietary Sodium Restriction

• Restrict dietary sodium to <2 g/day (<90 mmol/day or <5 g sodium chloride/day) 2, 3
• Salt restriction is particularly important in CKD and enhances RAS inhibitor effectiveness 2, 4, 3

Additional Lifestyle Measures

• Encourage lifestyle modifications including regular physical activity (e.g., walking 30 minutes daily) 4
• Achieve normal body mass index 6
• Smoking cessation 6

Critical Pitfalls to Avoid

Drug Combinations to Never Use

• NEVER combine ACE inhibitor + ARB as this increases adverse effects (hyperkalemia, acute kidney injury) without additional cardiovascular or renal benefits 1, 2, 3
• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor (Grade 1B) 1, 2

Agents to Avoid

• Avoid atenolol as it is less effective than placebo in reducing cardiovascular events 3
• Use calcium channel blockers cautiously in HIV-infected patients on protease inhibitors due to potential drug interactions causing hypotension 1

Excessive BP Lowering

• Avoid overly aggressive BP lowering resulting in diastolic BP <70 mm Hg as this compromises coronary perfusion and increases mortality 2
• Very low BP may lead to adverse events, particularly in elderly patients or those with stiff arteries 4

Special Considerations

• The evidence for intensive BP control is less robust in patients with advanced CKD (G4 or G5), proteinuria >1 g/day, or extremes of age 4
• The risk-benefit tradeoff should be carefully considered in these subpopulations 4

Blood Pressure Measurement Technique

Standardized Office Measurement

• Use standardized office BP measurement as routine office BP measurements are often unreliable 1, 4
• The BP targets specified above apply specifically to standardized measurements 1, 4

Alternative Monitoring Methods

• Ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) provide additional valuable information about BP control 4
• For children with CKD, monitor BP once yearly with ABPM and every 3-6 months with standardized auscultatory office BP 1