ACE Inhibitor and ARB Contraindications in CKD
The only absolute contraindication to ACE inhibitors and ARBs in CKD is bilateral renal artery stenosis (or stenosis in a solitary kidney). 1 Beyond this, these medications are not contraindicated but require careful monitoring and dose management based on specific clinical scenarios.
Absolute Contraindications
- Bilateral renal artery stenosis is the sole true contraindication, as ACE inhibitors and ARBs can precipitate acute kidney injury by preventing compensatory efferent arteriolar vasoconstriction in this setting 1
Dual RAAS Blockade: Explicitly Contraindicated
The combination of ACE inhibitors with ARBs must be avoided in all CKD patients. 1, 2, 3
- This combination increases risks of hyperkalemia and acute kidney injury without providing additional cardiovascular or renal benefits 1
- The VA NEPHRON-D trial definitively showed that combining lisinopril with losartan in diabetic CKD patients resulted in increased hyperkalemia and acute kidney injury without benefit on GFR decline, ESRD, or death 2
- FDA labeling explicitly states to avoid dual RAS blockade and contraindicate aliskiren co-administration in diabetic patients 2, 3
High-Risk Situations Requiring Intensive Monitoring (Not Absolute Contraindications)
Advanced CKD (eGFR <30 mL/min/1.73 m²)
- ACE inhibitors and ARBs remain beneficial even in advanced CKD but require closer monitoring 1
- Consider nephrology referral when eGFR falls below 30 mL/min/1.73 m² 1
- Do not discontinue based solely on eGFR decline—an initial creatinine rise of up to 30% is acceptable and typically returns to baseline 1
Hyperkalemia Risk
- Potassium-sparing diuretics (spironolactone, amiloride, triamterene) significantly increase hyperkalemia risk when combined with ACE inhibitors or ARBs 2, 3
- Monitor serum potassium closely when combining with mineralocorticoid receptor antagonists like finerenone, though this combination is recommended in diabetic CKD despite 10.8% hyperkalemia incidence (vs 5.3% placebo) 1, 4
- NSAIDs co-administration increases both hyperkalemia and acute kidney injury risk, particularly in elderly or volume-depleted patients 2, 3
Volume Depletion
- Initiation during aggressive diuretic therapy may cause excessive hypotension 3
- Consider reducing or temporarily holding diuretics, or increasing salt intake before starting ACE inhibitors/ARBs 3
Monitoring Requirements
Mandatory monitoring parameters include: 5, 6
- Serum creatinine: Check within 1-2 weeks of initiation and after dose changes; accept up to 30% increase 1
- Serum potassium: Monitor within 1 month of initiation, after dose adjustments, and periodically during therapy 4, 3
- Blood pressure: Assess for hypotension, especially in volume-depleted states 3
Common Pitfalls to Avoid
- Premature discontinuation: Past acute kidney injury, hyperkalemia episodes, or advanced CKD lead to inappropriate discontinuation in many patients who would benefit from continued therapy 7
- Inadequate potassium monitoring: Only 38% of CKD patients on ACE inhibitors/ARBs receive appropriate potassium monitoring despite 91.6% receiving creatinine monitoring 6
- Combining ACE inhibitors with ARBs: This remains a persistent error despite clear guideline recommendations against it 1, 8
Clinical Algorithm for Use
- Screen for bilateral renal artery stenosis if clinical suspicion exists (refractory hypertension, flash pulmonary edema, asymmetric kidney sizes) 1
- Choose either ACE inhibitor OR ARB, never both 1, 2, 3
- Start at standard or reduced doses depending on eGFR and volume status 3
- Monitor creatinine and potassium within 1-2 weeks 4, 5
- Accept creatinine increases up to 30% and continue therapy 1
- Optimize single-agent dosing rather than adding a second RAS blocker 8
- Consider adding calcium channel blocker or thiazide diuretic if additional blood pressure control needed 8