ACE Inhibitor Use at eGFR 38: Recommended with Appropriate Monitoring
Yes, ACE inhibitors can and should be added in a patient with eGFR 38 mL/min/1.73 m², particularly if the patient has heart failure, hypertension, diabetes with albuminuria, or proteinuric kidney disease. This eGFR level does not represent a contraindication to ACE inhibitor therapy, and the renoprotective and cardiovascular benefits typically outweigh the risks when properly monitored 1, 2.
Clinical Context Determines Strength of Indication
The appropriateness of ACE inhibitor therapy at eGFR 38 depends on the underlying condition:
Heart failure with reduced ejection fraction (HFrEF): ACE inhibitors are Class I recommended therapy regardless of renal function, as they reduce mortality and hospitalization 3. The 2013 ACC/AHA guidelines explicitly state that ACE inhibitors should be prescribed to all patients with HFrEF unless contraindicated 3.
Diabetes with albuminuria: ACE inhibitors should be initiated and titrated to maximum tolerated doses, as clinical trials demonstrating efficacy used maximal dosing, not low doses 3. The renoprotective benefit is dose-dependent and amplified by both diabetes and CKD 3.
Proteinuric CKD: Maximum-tolerated doses of ACE inhibitors provide renoprotection and should be continued even as eGFR declines 3, 1.
Hypertension alone: ACE inhibitors remain appropriate first-line agents at this eGFR level 2.
Dosing Strategy at eGFR 38
No dose adjustment is required for most ACE inhibitors when eGFR is above 30 mL/min/1.73 m² 4. The FDA label for lisinopril specifies that dose adjustment is only needed when creatinine clearance falls below 30 mL/min/1.73 m² 4.
- Start with standard initial doses (e.g., lisinopril 2.5-5 mg daily, enalapril 2.5 mg twice daily) 3
- Titrate gradually to target doses proven effective in clinical trials 3
- Target doses include lisinopril 20-40 mg daily or enalapril 10-20 mg twice daily 3
Essential Monitoring Protocol
Check serum creatinine and potassium within 1-2 weeks of initiation or dose adjustment, then periodically thereafter 3, 2:
- Accept creatinine rises up to 30% within the first 4 weeks—this hemodynamic adjustment predicts better long-term renal outcomes and does not require discontinuation 3, 1, 5
- Monitor potassium levels closely, as hyperkalemia risk increases with declining eGFR 3
- Assess blood pressure to avoid symptomatic hypotension 3
Managing Hyperkalemia Without Stopping Therapy
Hyperkalemia should be managed medically rather than by discontinuing the ACE inhibitor 1:
- Implement dietary potassium restriction 3
- Discontinue potassium supplements and avoid potassium-based salt substitutes 3
- Adjust or add diuretics if appropriate 1
- Consider potassium binders (e.g., patiromer, sodium zirconium cyclosilicate) to facilitate continuation of evidence-based therapy 3
- Reserve ACE inhibitor discontinuation only for uncontrolled hyperkalemia (>5.5-6.0 mEq/L) despite these interventions 3, 1
Critical Pitfalls to Avoid
Do not discontinue ACE inhibitors prematurely for modest creatinine elevations—the initial GFR decrease represents beneficial hemodynamic changes (reduced intraglomerular pressure through efferent arteriolar vasodilation) that provide long-term renoprotection 1, 5.
Ensure euvolemia before initiation—volume depletion significantly increases the risk of acute kidney injury with ACE inhibitors, particularly at lower eGFR levels 1, 5. The renal adverse effects and therapeutic benefits are both potentiated by sodium depletion 5.
Screen for bilateral renal artery stenosis if clinical suspicion exists (flash pulmonary edema, refractory hypertension, abdominal bruit)—this represents a true contraindication where ACE inhibitors can precipitate acute renal failure 1, 6.
Avoid combination therapy with ARBs or direct renin inhibitors—dual RAAS blockade increases hyperkalemia and adverse events without additional cardiovascular or renal benefit 3, 2.
When to Reduce Dose or Discontinue
Consider dose reduction or discontinuation only in specific scenarios 1:
- Serum creatinine rises >30% within 4 weeks of initiation or dose increase
- Symptomatic hypotension despite volume optimization
- Persistent hyperkalemia (>5.5 mEq/L) despite medical management
- Development of angioedema (absolute contraindication) 3
Complementary Therapy Considerations
Add an SGLT2 inhibitor if not already prescribed—these agents provide additive renoprotection and cardiovascular benefit at eGFR ≥20 mL/min/1.73 m², particularly in patients with diabetes or heart failure 3, 1. All major SGLT2 inhibitor trials demonstrating kidney benefit were conducted in patients already receiving maximum-tolerated ACE inhibitor or ARB therapy 3.
Consider adding a nonsteroidal MRA (finerenone) in patients with diabetes and albuminuria for additional renoprotection, though close potassium monitoring becomes even more critical 3.
Evidence Quality and Strength
The recommendation to continue ACE inhibitors at eGFR 38 is supported by the highest-quality guideline evidence. The 2024 Diabetes Care standards 3 and 2024 DCRM multispecialty recommendations 3 represent the most recent authoritative guidance, both explicitly supporting ACE inhibitor use at this eGFR level. The 2022 KDIGO-endorsed guidance 1, 2 provides specific thresholds indicating continuation is appropriate well below eGFR 38, with consideration for discontinuation only below eGFR 15 mL/min/1.73 m².
The cardiovascular mortality benefit at this eGFR level may actually exceed the benefit in patients with preserved renal function, as demonstrated in the PEACE trial where trandolapril reduced mortality specifically in patients with reduced eGFR (adjusted HR 0.73) but not in those with preserved renal function 7.