Can perindopril (Angiotensin-Converting Enzyme Inhibitor) and losartan (Angiotensin II Receptor Blocker) be given to a patient with Chronic Kidney Disease (CKD)?

Use of Perindopril and Losartan in Chronic Kidney Disease

Combination therapy with perindopril and losartan is not recommended for CKD patients due to increased risk of adverse effects including hyperkalemia, acute kidney injury, and hypotension without additional benefit compared to monotherapy.

Renin-Angiotensin System (RAS) Blockade in CKD

Single Agent Therapy

• ACE inhibitors (like perindopril) or ARBs (like losartan) are recommended as first-line therapy for CKD patients with hypertension and proteinuria 1
• Both medication classes have demonstrated renoprotective effects in CKD, particularly in patients with albuminuria 1
• Losartan has been shown to be effective in reducing blood pressure in patients with various stages of renal impairment, including those on hemodialysis 2
• Perindopril has demonstrated efficacy in CKD patients, with the PROGRESS study showing reduced risk of cardiovascular events in CKD patients 3

Dual RAS Blockade

• Dual blockade of the renin-angiotensin system with ACEi and ARB combination (such as perindopril and losartan together) is associated with increased risks of:

  • Hyperkalemia
  • Hypotension
  • Acute kidney injury
  • Changes in renal function
  • No additional benefit for cardiovascular or renal outcomes 4, 1

• The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial specifically showed that dual therapy with lisinopril and losartan provided no additional benefit compared to losartan monotherapy, but increased adverse events 4, 1

• The ONTARGET study similarly demonstrated no improvement in cardiovascular events with combination RAS blockade compared to monotherapy, while increasing risk of adverse effects 1

Dosing and Monitoring Considerations

For Perindopril

• Perindopril requires dose adjustment in CKD based on creatinine clearance 5
• In patients with renal insufficiency, perindoprilat (active metabolite) AUC increases with decreasing renal function:
  • At creatinine clearances of 30-80 mL/min, AUC is about double that of 100 mL/min
  • When creatinine clearance drops below 30 mL/min, AUC increases more markedly 5

For Losartan

• Losartan has been studied specifically in CKD patients and can be used across different stages of renal impairment 2
• Monitor for hyperkalemia, especially in advanced CKD 4

Monitoring Requirements

• Check serum potassium and creatinine within 2-4 weeks after initiating therapy with either agent 1, 6
• Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%) 1
• Stop ACEi or ARB if kidney function continues to worsen or refractory hyperkalemia develops 1

Alternative Approaches for CKD Patients

Recommended Alternatives

• If RAS blockade is needed, use either an ACEi OR an ARB, not both 1
• Many CKD patients require combination therapy to achieve target blood pressure of <120 mmHg systolic 6, 1
• Consider calcium channel blockers as add-on therapy rather than dual RAS blockade 6, 7
• Diuretics are often necessary in CKD management and can be combined with a single RAS blocker 1, 7

Special Considerations

• Loop diuretics are preferred over thiazides in patients with moderate-to-severe CKD (GFR <30 mL/min) 1
• Restrict dietary sodium to <2.0 g/d (<90 mmol/d) in CKD patients 1, 8
• Counsel patients to temporarily hold ACEi or ARB during illness with risk of volume depletion, prior to procedures with contrast, or before major surgery 1, 3

Conclusion

When managing hypertension and proteinuria in CKD patients, either perindopril or losartan can be used as monotherapy, but they should not be used in combination due to increased risk of adverse effects without additional benefit.