What is the best management approach for a patient with chronic kidney disease (CKD) and hypertension?

Management of CKD Stage 4 with Hypertension

For this patient with CKD Stage 4 (eGFR 28) and hypertension, target a systolic blood pressure <120 mmHg using standardized office measurement, initiate an ACE inhibitor or ARB as first-line therapy (particularly if albuminuria is present), and aggressively implement lifestyle modifications including sodium restriction to <2g/day. 1

Blood Pressure Target

• Target systolic BP <120 mmHg when tolerated, using standardized office BP measurement to reduce cardiovascular events and slow CKD progression 1
• The 2024 ESC guidelines recommend targeting systolic BP to 120-129 mmHg in adults with moderate-to-severe CKD (eGFR >30 mL/min/1.73 m²) who are receiving BP-lowering drugs, if tolerated 1
• For patients with eGFR 28 mL/min/1.73 m², individualized BP targets are appropriate given proximity to advanced CKD, though the <120 mmHg target remains the guideline recommendation when tolerated 1

Critical caveat: It is potentially hazardous to apply the <120 mmHg target to BP measurements obtained in a non-standardized manner—proper technique with automated office BP (AOBP) or standardized manual measurement is essential 1

Pharmacologic Management Algorithm

Step 1: Determine Albuminuria Status and Initiate RAS Blockade

• If severely increased albuminuria is present (ACR >300 mg/g or >30 mg/mmol), start an ACE inhibitor or ARB immediately as this is a Level 1B strong recommendation 1
• If moderately increased albuminuria is present (ACR 30-300 mg/g or 3-30 mg/mmol), start an ACE inhibitor or ARB (Level 2C suggestion) 1
• Even without albuminuria, it may be reasonable to treat with RAS inhibition given the cardiovascular and renal protective benefits 1

RAS inhibitor dosing principles:

• Use the highest approved dose that is tolerated, as proven benefits were achieved in trials using maximal doses 1
• Check BP, serum creatinine, and potassium within 2-4 weeks of initiation or dose increase 1
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation 1
• Never combine ACE inhibitor + ARB + direct renin inhibitor—this triple combination is contraindicated 1

Step 2: Add Additional Agents to Reach Target

• Add a diuretic as the second agent since volume management is critical in CKD-related hypertension 2, 3
• At eGFR 28, thiazide diuretics become less effective—use loop diuretics (furosemide) for adequate diuresis 4
• If BP remains above target, add a long-acting dihydropyridine calcium channel blocker (amlodipine) which has demonstrated cardiovascular mortality benefit in CKD patients 5, 6
• Dihydropyridine CCBs should always be combined with RAS blockade in proteinuric patients, never used as monotherapy 2

Step 3: Consider Additional Agents for Resistant Hypertension

• If BP remains >140/90 mmHg despite triple therapy at appropriate doses, add spironolactone 25 mg daily as the most effective fourth-line agent 4, 5
• Monitor potassium closely with mineralocorticoid receptor antagonists, particularly at this level of kidney function 1
• Beta-blockers (carvedilol, labetalol) should be added if coronary artery disease or heart failure is present 5, 2

Lifestyle Modifications (Essential Foundation)

Dietary Sodium Restriction

• Target sodium intake <2g/day (or <90 mmol/day, equivalent to <5g sodium chloride/day) 1
• This is the single most important dietary intervention for BP control in CKD 7, 8
• Provide intensive dietary counseling emphasizing fresh foods over processed foods 9, 3

Physical Activity

• Recommend moderate-intensity physical activity for cumulative duration of at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance 1
• Walking and aerobic exercise have been shown to slow CKD progression 7, 8
• Consider cardiorespiratory fitness status, physical limitations, and fall risk when prescribing exercise intensity 1

Weight Management and Other Factors

• Weight loss in patients with BMI >25 kg/m² helps reduce BP 3
• Smoking cessation is mandatory—tobacco use accelerates CKD progression 7, 8
• Limit alcohol consumption to moderate intake 1, 3

Important caveat: DASH-type diet or potassium-rich salt substitutes may not be appropriate at eGFR 28 due to hyperkalemia risk 1

Monitoring Strategy

• Use out-of-office BP monitoring (home BP or 24-hour ambulatory BP monitoring) to complement office readings and avoid white coat hypertension or masked hypertension 1
• Monitor serum creatinine and potassium within 2-4 weeks after any medication change 1
• Hyperkalemia associated with RAS inhibition can often be managed with potassium-lowering measures rather than stopping the RAS inhibitor, given its critical renal and cardiovascular protective effects 1
• Assess for orthostatic hypotension, particularly if symptomatic hypotension develops 1

Common Pitfalls to Avoid

• Do not use routine (non-standardized) office BP measurements to guide intensive BP lowering to <120 mmHg—this can lead to overtreatment and adverse events 1
• Do not combine ACE inhibitor + ARB—dual RAS blockade increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 1
• Do not rely on thiazide diuretics alone at this level of kidney function (eGFR 28)—loop diuretics are required for effective volume management 4, 10
• Do not discontinue RAS inhibition for creatinine increases <30% within 4 weeks, as modest increases are expected and acceptable 1
• Clinicians can reasonably offer less intensive BP-lowering therapy in patients with very limited life expectancy or symptomatic postural hypotension 1