Should a nephrologist ever prescribe both an Angiotensin-Converting Enzyme (ACE) inhibitor and an Angiotensin Receptor Blocker (ARB) to a dialysis patient?

Dual ACE Inhibitor and ARB Therapy in Dialysis Patients

Nephrologists should not prescribe the combination of an ACE inhibitor and an ARB to dialysis patients due to increased risks of hyperkalemia and adverse events without additional clinical benefit. 1, 2, 3

Evidence Against Dual RAS Blockade

The 2019 KDOQI US Commentary on the ACC/AHA Hypertension Guideline explicitly states that "simultaneous use of an ACE inhibitor, ARB, and/or renin inhibitor is potentially harmful and is not recommended to treat adults with hypertension" (COR III: Harm, LOE A) 1. This recommendation applies to all patients, including those on dialysis.

The FDA drug labels for both ACE inhibitors and ARBs contain specific warnings against dual RAS blockade:

• Losartan (ARB) label warns that "dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy" 2
• Lisinopril (ACE inhibitor) label similarly warns against combined use of RAS inhibitors 3

Specific Risks in Dialysis Patients

Dialysis patients are at particularly high risk of complications from dual RAS blockade:

1. Hyperkalemia risk: While some studies show variable effects on potassium levels with single-agent RAS blockade in dialysis patients 4, 5, the risk significantly increases with dual therapy.

2. Hemodynamic instability: Dialysis patients already experience significant hemodynamic shifts during treatment, and dual RAS blockade can exacerbate hypotension 1, 2.

3. No proven benefit: The Canadian Society of Nephrology commentary on KDIGO guidelines states that "evidence that the combination alters clinically important outcomes is lacking, even in heavily proteinuric patients, and that adverse effects are increased" 1.

Single-Agent RAS Blockade in Dialysis

For dialysis patients requiring RAS blockade, a single agent (either ACE inhibitor OR ARB) may be appropriate in certain circumstances:

• For cardiovascular protection in patients with heart failure or coronary artery disease 1
• For blood pressure management when other agents are contraindicated or ineffective

When using a single RAS-blocking agent in dialysis patients:

1. Monitor potassium levels closely, especially after initiation and dose adjustments 1, 6
2. Be cautious in anuric patients who may have higher risk of hyperkalemia 7
3. Consider dialysate potassium concentration adjustments if needed 7

Alternatives for Hypertension Management in Dialysis

For hypertension management in dialysis patients, preferred alternatives to dual RAS blockade include:

• Calcium channel blockers (particularly dihydropyridines)
• Beta-blockers (especially in patients with heart failure or coronary disease)
• Appropriate volume management through ultrafiltration
• Careful use of diuretics in patients with residual renal function

Conclusion

The evidence strongly advises against dual ACE inhibitor and ARB therapy in dialysis patients. This combination increases risks without providing additional benefit compared to single-agent therapy. When RAS blockade is indicated, use either an ACE inhibitor OR an ARB with appropriate monitoring, but never both simultaneously.