What is the recommended management for hypertension in patients with Chronic Kidney Disease (CKD)?

Management of Hypertension in CKD Patients

Target a systolic blood pressure <120 mmHg using standardized office measurement in adults with CKD not on dialysis, and initiate ACE inhibitors or ARBs as first-line therapy, particularly when albuminuria is present. 1

Blood Pressure Targets

The KDIGO 2021 guideline recommends treating adults with CKD to a target SBP <120 mmHg when tolerated, based on cardiovascular and survival benefits demonstrated in the SPRINT trial. 1 This target applies specifically to standardized office BP measurements—not routine casual readings—and is critical because the relationship between routine and standardized BP is highly variable. 1

• This recommendation does not apply to kidney transplant recipients (target <130/80 mmHg) or dialysis patients. 1
• For older adults ≥65 years with CKD, a more conservative target of 130-139 mmHg systolic may be safer and more appropriate. 2
• The <120 mmHg target provides cardioprotective and survival benefits but no renoprotective effect. 1
• Less intensive BP-lowering is reasonable for patients with very limited life expectancy or symptomatic postural hypotension. 1

Common pitfall: Applying the <120 mmHg target to non-standardized BP measurements is potentially hazardous. 1 Standardized measurement requires proper patient preparation, appropriate equipment (preferably automated oscillometric devices), and correct technique. 1

First-Line Pharmacological Therapy

Start renin-angiotensin system inhibitors (ACE inhibitors or ARBs) as first-line therapy for CKD patients with hypertension and albuminuria. 1, 3

Specific Indications by Albuminuria Status:

• Severely increased albuminuria (A3) without diabetes (CKD G1-G4): ACE inhibitor or ARB (strong recommendation, 1B). 1
• Moderately increased albuminuria (A2) without diabetes (CKD G1-G4): ACE inhibitor or ARB (weak recommendation, 2C). 1
• Moderately-to-severely increased albuminuria (A2 and A3) with diabetes (CKD G1-G4): ACE inhibitor or ARB (strong recommendation, 1B). 1, 3
• No albuminuria (with or without diabetes): RAS inhibitors may be reasonable but evidence is less robust. 1

Uptitrate ACE inhibitors or ARBs to maximally tolerated doses despite modest creatinine increases. 3 A creatinine rise ≤30% within 4 weeks of initiation or dose increase is acceptable and reflects hemodynamic changes, not harm. 3 Continue the medication unless creatinine rises >30%. 3

Monitoring Requirements:

• Check serum creatinine and potassium within 2-4 weeks of initiating or increasing RAS inhibitor dose. 3, 2
• Critical contraindication: Never combine ACE inhibitor + ARB + direct renin inhibitor—this triple combination increases adverse events without benefit. 1, 4

Second-Line and Add-On Therapy

For inadequate BP control on RAS inhibitor monotherapy, add a dihydropyridine calcium channel blocker (CCB) or thiazide/thiazide-like diuretic. 3, 2

• Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD but always combined with a RAS blocker. 5
• Non-dihydropyridine CCBs consistently reduce albuminuria and slow kidney function decline. 5

Diuretic Selection by Kidney Function:

• GFR ≥30 mL/min: Thiazide or thiazide-like diuretics are effective. 3, 2
• GFR <30 mL/min or creatinine >2.0 mg/dL: Loop diuretics are required as thiazides become ineffective. 3
• Use twice-daily dosing of loop diuretics over once-daily, and increase dose until clinically significant diuresis or maximum effective dose is reached. 3

Resistant Hypertension:

For resistant hypertension, add low-dose spironolactone with close monitoring of potassium and renal function, especially if eGFR <45 mL/min. 3, 6 Chlorthalidone is an effective alternative for stage 4 CKD patients with uncontrolled hypertension and can mitigate hyperkalemia risk when used with spironolactone, though careful monitoring is essential. 6

Lifestyle Modifications

Restrict dietary sodium to <2 g sodium per day (<90 mmol/day or <5 g sodium chloride/day). 1, 2 Salt restriction is particularly important in CKD patients and enhances the effectiveness of RAS inhibitors. 3, 2

• Exception: Dietary sodium restriction is not appropriate for patients with sodium-wasting nephropathy. 1
• Caution: DASH diet or potassium-rich salt substitutes may not be appropriate for advanced CKD patients due to hyperkalemia risk. 1, 2

Advise moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance. 1 Consider cardiorespiratory fitness, physical limitations, cognitive function, and fall risk when prescribing exercise intensity. 1

Blood Pressure Measurement Technique

Use standardized office BP measurement rather than routine casual readings. 1, 2 Standardization emphasizes adequate patient preparation and proper technique, not necessarily the type of equipment. 1

• Automated office BP (AOBP), either attended or unattended, may be the preferred method. 1
• Oscillometric devices can be used even in patients with atrial fibrillation. 1
• Complement standardized office readings with out-of-office BP monitoring (ambulatory or home BP monitoring). 1

Special Populations

Kidney Transplant Recipients:

• Target BP <130/80 mmHg (not <120 mmHg). 1
• Start with dihydropyridine CCB or ARB as first-line therapy. 1, 3

Black Patients:

• Initial therapy should include diuretic or CCB, alone or combined with RAS inhibitor. 3

Patients with Diabetes:

• Evidence for <120 mmHg target is less certain; 130-139 mmHg systolic may be acceptable. 1, 2

Advanced CKD (G4-G5):

• Evidence supporting <120 mmHg target is less certain in this subgroup. 1
• Careful monitoring for acute kidney injury and electrolyte abnormalities is essential. 1

Critical Pitfalls to Avoid

• Do not discontinue ACE inhibitors/ARBs for creatinine increases up to 30%—this is expected and acceptable. 3
• Avoid NSAIDs, potassium supplements, and salt substitutes while on RAS inhibitors. 3
• Do not combine ACE inhibitor + ARB + direct renin inhibitor. 1, 4
• Avoid overly aggressive BP lowering resulting in diastolic BP <70 mmHg, which may compromise coronary perfusion. 2
• RAS inhibitors are contraindicated in pregnancy. 3