What are the recommended drugs and doses for managing hypertension in Chronic Kidney Disease (CKD) Stage 5?

Management of Hypertension in CKD Stage 5: Recommended Drugs and Doses

In CKD Stage 5 (eGFR <15 mL/min/1.73 m²), consider reducing the dose or discontinuing ACE inhibitors or ARBs to manage symptomatic hypotension, uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure. 1

Blood Pressure Target

• Target systolic BP <120 mmHg when tolerated using standardized office BP measurement 1
• Alternatively, a systolic BP range of 130-139 mmHg is acceptable 1
• Critical caveat: These BP targets apply only to standardized office measurements; applying the <120 mmHg target to non-standardized measurements is potentially hazardous 1
• Less intensive BP-lowering therapy is reasonable in patients with very limited life expectancy or symptomatic postural hypotension 1

First-Line Antihypertensive Agents

ACE Inhibitors or ARBs

ACE inhibitors or ARBs should be administered at the highest approved dose that is tolerated, as proven benefits were achieved in trials using these doses. 1

Lisinopril Dosing in CKD Stage 5:

• For hemodialysis patients or creatinine clearance <10 mL/min: Initial dose 2.5 mg once daily 2
• Maximum dose: Up-titrate as tolerated to 40 mg daily 2

Losartan Dosing:

• Standard starting dose: 50 mg once daily 3
• Can increase to maximum 100 mg once daily as needed 3
• Note: No specific renal dose adjustment listed in FDA labeling for Stage 5 CKD, but clinical judgment and monitoring are essential 3

Monitoring Parameters for RAS Inhibitors

• Check serum creatinine and potassium within 2-4 weeks of initiation or dose increase 1, 4
• Continue therapy if creatinine rises ≤30% within 4 weeks, as this reflects hemodynamic changes and does not indicate harm 1, 4
• Discontinue if creatinine rises >30% within 4 weeks of initiation or dose increase 1

When to Reduce or Discontinue RAS Inhibitors in Stage 5:

• Symptomatic hypotension despite management 1
• Uncontrolled hyperkalemia despite medical treatment 1
• To reduce uremic symptoms while treating kidney failure (eGFR <15 mL/min/1.73 m²) 1

Second-Line and Additional Agents

Loop Diuretics (Essential in Stage 5)

• Loop diuretics are required when GFR <30 mL/min or serum creatinine >2.0 mg/dL, as thiazides become ineffective 4
• Use twice-daily dosing over once-daily 4
• Increase dose until clinically significant diuresis or maximum effective dose is reached 4

Calcium Channel Blockers

• Dihydropyridine CCBs (e.g., amlodipine, nifedipine) can be added as second-line therapy 4
• For kidney transplant recipients specifically, dihydropyridine CCB or ARB is recommended as first-line 1

Mineralocorticoid Receptor Antagonists

• Spironolactone is effective for refractory hypertension but carries significant risk of hyperkalemia and reversible decline in kidney function, particularly in patients with low eGFR 1
• Use low-dose spironolactone with close monitoring of potassium and renal function 4
• This option requires extreme caution in Stage 5 CKD due to high hyperkalemia risk 1

Management of Hyperkalemia

• Hyperkalemia associated with RAS inhibitors can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the RAS inhibitor 1
• Avoid NSAIDs, potassium supplements, and salt substitutes while on RAS inhibitors 4

Contraindicated Combinations

Never combine ACE inhibitor + ARB + direct renin inhibitor, as this triple combination increases adverse events without benefit 1

Non-Pharmacological Management

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to enhance diuretic efficacy and BP control 4
• Reducing dietary sodium to 2.3 g/day is critical to optimize medication effectiveness 1

Typical Multi-Drug Regimen

Most CKD Stage 5 patients require 3 or more antihypertensive agents to achieve BP control 1:

1. ACE inhibitor or ARB (at maximally tolerated dose, with consideration for dose reduction or discontinuation in Stage 5 based on clinical status) 1, 4
2. Loop diuretic (mandatory in Stage 5) 4
3. Dihydropyridine CCB 4
4. Consider spironolactone for resistant hypertension with intensive monitoring 4

Common Pitfalls to Avoid

• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30% 1, 4
• Do not use thiazide diuretics as monotherapy in Stage 5 CKD; they are ineffective 4
• Do not apply intensive BP targets (<120 mmHg) to non-standardized BP measurements 1
• RAS inhibitors are contraindicated in pregnancy 4