What is the approach to using Angiotensin-Converting Enzyme (ACE) inhibitors in a patient with impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 20?

ACE Inhibitor Use in Advanced CKD (eGFR 20)

Continue ACE inhibitor therapy in patients with eGFR 20 mL/min/1.73 m², particularly if albuminuria is present, as the renoprotective and cardiovascular benefits outweigh risks when properly monitored. 1

Primary Recommendation

• ACE inhibitors should be continued even when eGFR falls below 30 mL/min/1.73 m², including at eGFR 20, unless specific contraindications develop 1
• The 2025 KDIGO guidelines explicitly state to continue ACE inhibitor or ARB therapy in CKD patients even as eGFR declines to this level 1
• This recommendation applies regardless of whether the patient has diabetes, as long as moderately-to-severely increased albuminuria (A2 or A3) is present 1

Monitoring Requirements at eGFR 20

Check serum creatinine, potassium, and blood pressure within 2-4 weeks of any dose initiation or adjustment, with more frequent monitoring given the low eGFR 1

Key monitoring parameters:

• Accept up to 30% rise in serum creatinine within 4 weeks - this is expected and does not require discontinuation 1
• Monitor potassium closely - hyperkalemia is more likely at eGFR 20 but should be managed medically rather than stopping the ACE inhibitor 1
• Assess for symptomatic hypotension - volume status becomes critical at this eGFR level 1

When to Reduce Dose or Discontinue

Consider reducing dose or stopping ACE inhibitor only in these specific scenarios: 1

• Serum creatinine rises >30% within 4 weeks of initiation or dose increase 1
• Symptomatic hypotension that cannot be managed with volume adjustment 1
• Uncontrolled hyperkalemia despite medical treatment (potassium-lowering measures should be attempted first) 1
• eGFR falls below 15 mL/min/1.73 m² with uremic symptoms requiring management 1

Dosing Considerations

Reduce initial doses and titrate slowly in patients with eGFR 20 2, 3:

• Captopril: Start at lower doses (6.25-12.5 mg TID) rather than standard 25 mg TID, with slow titration over 1-2 week intervals 2
• Lisinopril: Dosing should be adjusted for impaired renal function, as elimination half-life increases when GFR <30 mL/min 3
• Use loop diuretics (furosemide) rather than thiazides if concurrent diuretic therapy is needed at this eGFR level 2

Managing Hyperkalemia Without Stopping ACE Inhibitor

Hyperkalemia should be managed with potassium-lowering strategies rather than discontinuing the ACE inhibitor: 1

• Dietary potassium restriction
• Diuretic adjustment (loop diuretics preferred)
• Potassium binders if needed
• Discontinuation should be reserved only for uncontrolled hyperkalemia despite these measures 1

Combination Therapy at eGFR 20

Add SGLT2 inhibitor if eGFR ≥20 mL/min/1.73 m² for additional renoprotection and cardiovascular benefit, particularly in diabetic patients 1:

• SGLT2 inhibitors are recommended at eGFR ≥20 with albuminuria ≥200 mg/g or heart failure 1
• Can be continued even if eGFR subsequently falls below 20 unless dialysis is initiated 1
• Never combine ACE inhibitor with ARB or direct renin inhibitor - this is explicitly contraindicated 1

Critical Pitfalls to Avoid

Do not discontinue ACE inhibitor for modest creatinine rises - the initial decrease in GFR (up to 30%) represents hemodynamic adjustment and predicts better long-term renal outcomes 1, 4

Avoid volume depletion - at eGFR 20, patients are particularly susceptible to ACE inhibitor-induced acute kidney injury when volume depleted 4, 5:

• Assess volume status before initiating or increasing doses
• Adjust diuretics appropriately
• Monitor for dehydration during intercurrent illness

Screen for bilateral renal artery stenosis - though rare, this represents a true contraindication where ACE inhibitors can cause acute renal failure 1, 6, 5:

• Consider if resistant hypertension or unexplained acute kidney injury occurs
• Angiotensin II maintains GFR in post-stenotic kidneys by efferent arteriolar constriction 6

Rationale for Continuation

The renoprotective mechanism of ACE inhibitors - reducing intraglomerular pressure through efferent arteriolar vasodilation - is precisely what causes the initial GFR decline but provides long-term benefit 4, 7:

• The fall in filtration pressure reduces proteinuria 4
• Long-term studies show correlation between initial GFR reduction and better renal outcomes 4
• Benefits in slowing CKD progression persist even at advanced stages 1

Cardiovascular protection remains critical at eGFR 20, as cardiovascular mortality exceeds risk of progression to dialysis in this population 1