How should hypertension be managed in a patient with stage 5 chronic kidney disease (estimated glomerular filtration rate < 15 mL/min/1.73 m²)?

Management of Hypertension in Stage 5 Chronic Kidney Disease

In stage 5 CKD (eGFR <15 mL/min/1.73 m²), target blood pressure to <130/80 mmHg using ACE inhibitors or ARBs as first-line therapy, continuing these agents even at very low eGFR levels unless dialysis is initiated or intolerable side effects develop. 1, 2

Blood Pressure Target

• The blood pressure goal is <130/80 mmHg for all patients with stage 5 CKD. 1, 2
• This target applies regardless of whether the patient has diabetes or proteinuria 2
• Some evidence suggests even lower targets (mean arterial pressure <92 mmHg, equivalent to approximately 120/80 mmHg) may provide additional long-term kidney protection, though this is based on post-hoc analyses 2

First-Line Pharmacologic Therapy

ACE inhibitors or ARBs remain the cornerstone of hypertension management in stage 5 CKD. 3, 1, 2

Initiation and Dosing Strategy

• Start with an ACE inhibitor (e.g., lisinopril 2.5 mg daily in stage 5 CKD) or ARB as first-line therapy 4
• For patients with creatinine clearance <10 mL/min or on hemodialysis, the recommended initial lisinopril dose is 2.5 mg once daily 4
• Continue ACE inhibitors or ARBs even when eGFR falls below 15 mL/min/1.73 m² unless dialysis is initiated or side effects are intolerable 3, 1

Monitoring After Initiation or Dose Adjustment

• Check serum creatinine and potassium within 5-7 days after starting or adjusting ACE inhibitor/ARB doses 1
• Recheck these parameters within 2-4 weeks depending on current GFR and potassium levels 3

When to Continue vs. Discontinue

• Continue therapy if creatinine rises <30% within 4 weeks of initiation or dose increase 3, 1
• Discontinue or reduce dose if:
  • Creatinine rises >30% from baseline within 4 weeks 3, 1
  • Potassium exceeds 5.5 mEq/L (or mmol/L) despite medical management 3, 1
  • Symptomatic hypotension occurs 3
  • Uncontrolled hyperkalemia persists despite treatment 3

Managing Hyperkalemia Without Stopping ACE Inhibitors/ARBs

• Hyperkalemia can often be managed with potassium-lowering measures rather than discontinuing the ACE inhibitor/ARB 3
• Dietary potassium restriction to 2-3 g per day 1
• Consider potassium binders or other medical management before abandoning renin-angiotensin system blockade 3

Additional Antihypertensive Agents

Most patients with stage 5 CKD require multiple agents to achieve blood pressure targets. 2

Diuretics

• Add a loop diuretic (not thiazides) as the second agent after ACE inhibitor/ARB 2
• Thiazide diuretics are ineffective when GFR <30 mL/min and should not be used 1
• Loop diuretics remain effective even at very low GFR levels 2

Subsequent Agents (in order of addition)

1. Beta-blockers (third-line) 2
2. Calcium channel blockers (fourth-line) 2
3. Alpha-blockers (fifth-line) 2
4. Alpha-2 agonists (e.g., clonidine) (sixth-line) 2
5. Vasodilators (e.g., minoxidil) (final option) 2

Non-Pharmacologic Management

Dietary sodium restriction to <2 g sodium per day (<5 g sodium chloride) is essential and often underutilized. 1, 2

Additional lifestyle modifications include: 2

• Moderate alcohol intake
• Regular exercise
• Weight loss if BMI >25 kg/m²
• Reduced saturated fat intake

Monitoring Schedule in Stage 5 CKD

• Serum creatinine and eGFR: every 3 months 1
• Serum potassium: every 3 months, more frequently when on ACE inhibitors/ARBs 1
• Blood pressure: monitor closely with both clinic and home measurements 2

Critical Pitfalls to Avoid

Do NOT Discontinue ACE Inhibitors/ARBs Prematurely

• A creatinine rise <30% is expected hemodynamic effect, not kidney injury 3, 1
• Many clinicians inappropriately stop these agents at the first sign of creatinine elevation, depriving patients of cardiovascular and residual kidney protection 3

Do NOT Use Thiazide Diuretics

• Thiazides are completely ineffective when GFR <30 mL/min 1
• Use loop diuretics instead 2

Do NOT Avoid NSAIDs Entirely

• NSAIDs worsen renal function and increase hyperkalemia risk in stage 5 CKD and should be avoided 1

Do NOT Base Treatment Decisions on Serum Creatinine Alone

• Always calculate eGFR using validated equations (MDRD or CKD-EPI) that account for age, sex, race, and body size 1, 5
• Creatinine-based estimates are particularly inaccurate at very low GFR levels 6

Special Considerations for Dialysis Timing

Blood pressure management should not dictate dialysis initiation timing. 1, 7, 6

• Dialysis should be initiated based on clinical symptoms (uremic symptoms, refractory fluid overload, uncontrolled hypertension despite maximal therapy, progressive malnutrition, severe electrolyte abnormalities), not GFR threshold alone 1, 7, 6
• Early dialysis initiation (eGFR >10 mL/min/1.73 m²) provides no mortality benefit and may accelerate loss of residual kidney function 7, 6
• Consider reducing or discontinuing ACE inhibitors/ARBs to reduce uremic symptoms when eGFR <15 mL/min/1.73 m² if dialysis is being delayed for clinical reasons 3

Evidence Strength and Nuances

The recommendation to continue ACE inhibitors/ARBs in stage 5 CKD represents a shift from older practice patterns. The 2024 KDIGO guidelines explicitly state to continue these agents even below eGFR 15 mL/min/1.73 m² 3, supported by the 2022 ADA/KDIGO diabetes consensus 3. This contrasts with earlier conservative approaches that recommended stopping at stage 4-5 CKD. The evidence shows antihypertensive therapy can actually improve eGFR in some CKD patients 8, and the cardiovascular benefits outweigh concerns about modest creatinine elevations 3.