What is the approach to using Angiotensin-Converting Enzyme (ACE) inhibitors in a patient with Chronic Kidney Disease (CKD) and an estimated Glomerular Filtration Rate (eGFR) of 4?

ACE Inhibitor Management in CKD with eGFR of 4

Primary Recommendation

Consider reducing the dose or discontinuing the ACE inhibitor in a patient with eGFR of 4 mL/min/1.73 m², particularly if uremic symptoms, uncontrolled hyperkalemia, or symptomatic hypotension are present. 1, 2

Clinical Decision Algorithm

Step 1: Assess Clinical Tolerance

Immediately evaluate the following parameters:

• Serum potassium level - Check for hyperkalemia (>5.5 mEq/L) 1
• Blood pressure - Document symptomatic hypotension (systolic BP ≤90 mmHg) or asymptomatic low readings 2
• Uremic symptoms - Assess for nausea, vomiting, altered mental status, pruritus 2
• Recent creatinine trends - Review for hemodynamic intolerance patterns 2

Step 2: Decision Points for Continuation vs. Discontinuation

Continue ACE inhibitor if ALL of the following are true:

• Patient tolerating medication well without symptomatic hypotension 2
• Potassium levels are manageable (can be controlled with dietary restriction, potassium binders, or diuretic adjustment) 1
• No severe uremic symptoms present 2
• Cardiovascular and renal protective benefits still outweigh risks 2

Reduce dose or discontinue if ANY of the following are present:

• Uncontrolled hyperkalemia despite medical management (potassium binders, dietary restriction, diuretic optimization) 1
• Symptomatic hypotension 1
• Uremic symptoms that may be reduced by discontinuation 1
• Serum creatinine rise >30% within 4 weeks of initiation or dose increase 1

Critical Monitoring Requirements

Within 2-4 weeks of any dose adjustment or continuation decision, check: 1

• Serum creatinine
• Serum potassium
• Blood pressure measurements

Hyperkalemia Management Strategy

Before discontinuing ACE inhibitor for hyperkalemia, attempt these interventions: 1

• Eliminate all potassium supplements and potassium-based salt substitutes 2
• Counsel on limiting high-potassium foods 2
• Consider potassium binders (patiromer, sodium zirconium cyclosilicate)
• Optimize diuretic therapy if volume overloaded
• Only discontinue if hyperkalemia remains uncontrolled despite these measures 1

Important Caveats and Pitfalls

The 2024 KDIGO guidelines explicitly state to continue ACE inhibitors even when eGFR falls below 30 mL/min/1.73 m² 1, 3, but Practice Point 3.6.5 provides the specific exception for eGFR <15 mL/min/1.73 m² when uremic symptoms, uncontrolled hyperkalemia, or symptomatic hypotension are present 1.

At eGFR of 4, the patient is in CKD G5 (kidney failure) and likely approaching dialysis initiation. The pharmacokinetics of ACE inhibitors are significantly altered at this level of renal function, with prolonged half-life and increased drug accumulation 4, 5. Lisinopril elimination becomes clinically impaired when GFR is below 30 mL/min 4.

Research evidence shows conflicting outcomes: One observational study found that discontinuing ACE inhibitors in advanced CKD (stages 4-5) led to improved eGFR and delayed dialysis initiation 6. However, the higher-quality 2022 STOP ACEi randomized controlled trial (411 patients with eGFR <30) found no significant difference in long-term eGFR between discontinuation and continuation groups, and there was a trend toward more ESKD events in the discontinuation group (62% vs 56%, HR 1.28) 7.

Never combine ACE inhibitors with ARBs or direct renin inhibitors - dual RAS blockade is contraindicated and increases risks of hyperkalemia, hypotension, and acute kidney injury 1, 2.

Complementary Medication Considerations at eGFR 4

• SGLT2 inhibitors: Generally not initiated at eGFR <20 mL/min/1.73 m², but if already prescribed, can be continued until dialysis 2, 3
• Nonsteroidal MRAs (finerenone): Contraindicated at eGFR <25 mL/min/1.73 m² 2, 3
• Statin therapy: Should be continued or initiated for cardiovascular protection 3

Practical Approach

Given the 2024 KDIGO guideline recommendations and the neutral findings from the STOP ACEi trial, the most evidence-based approach is:

1. Default to continuation if the patient is clinically stable without the three key contraindications (uremic symptoms, uncontrolled hyperkalemia, symptomatic hypotension) 1, 2, 7
2. Reduce dose or discontinue if any of these three conditions are present and cannot be managed with supportive measures 1
3. Prepare for dialysis initiation as eGFR of 4 indicates imminent need for renal replacement therapy 1