At what level of Glomerular Filtration Rate (GFR) should Angiotensin-Converting Enzyme inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs) be stopped in patients with Chronic Kidney Disease (CKD)?

ACE Inhibitor/ARB Discontinuation Based on GFR

There is no specific GFR threshold at which ACE inhibitors or ARBs should be routinely stopped; instead, continue these medications even when eGFR falls below 30 mL/min/1.73 m² and only consider dose reduction or discontinuation at eGFR <15 mL/min/1.73 m² if specific complications develop: symptomatic hypotension, uncontrolled hyperkalemia despite medical management, or uremic symptoms. 1

Continue ACE/ARB Through Advanced CKD

• The 2024 KDIGO guidelines explicitly state to continue ACE inhibitors or ARBs even when eGFR falls below 30 mL/min/1.73 m². 1
• The highest quality randomized trial (STOP-ACEi, 2022) demonstrated that discontinuing RAS inhibitors in patients with eGFR <30 mL/min/1.73 m² provided no benefit—the eGFR at 3 years was similar whether patients stopped or continued therapy (12.6 vs 13.3 mL/min/1.73 m²). 2
• Patients who discontinued ACE inhibitors had higher rates of kidney failure or need for kidney replacement therapy (65% vs 54%, hazard ratio 1.52). 3

Specific Threshold for Consideration of Discontinuation

• Consider reducing dose or discontinuing only when eGFR <15 mL/min/1.73 m² AND one of these three conditions is present: 1, 4
  • Symptomatic hypotension (not just low blood pressure readings, but symptoms like dizziness, syncope, or falls)
  • Uncontrolled hyperkalemia despite medical treatment (potassium-lowering measures including dietary restriction, diuretics, sodium bicarbonate, or potassium binders)
  • Uremic symptoms requiring palliation (nausea, vomiting, altered mental status, pruritus)

Acceptable Creatinine Rise After Initiation

• Continue ACE/ARB therapy unless serum creatinine rises by MORE than 30% within 4 weeks of starting or increasing the dose. 1
• A creatinine rise up to 30% reflects the desired hemodynamic effect of reducing intraglomerular pressure and is not acute kidney injury. 1
• The ACCORD-BP trial demonstrated that patients with up to 30% creatinine increase had no increased mortality or progressive kidney disease. 1

Managing Hyperkalemia Without Stopping ACE/ARB

• Hyperkalemia should be managed with potassium-lowering measures rather than immediately stopping the ACE/ARB. 1
• Specific interventions include: 1
  • Moderate dietary potassium intake
  • Add or increase diuretics
  • Sodium bicarbonate supplementation
  • Gastrointestinal cation exchangers (patiromer or sodium zirconium cyclosilicate)
• Only reduce dose or stop ACE/ARB as a last resort when hyperkalemia remains uncontrolled despite these measures. 1

Monitoring Protocol

• Check serum creatinine and potassium within 2-4 weeks after initiation or any dose increase. 1
• The timing depends on baseline eGFR and potassium level—check sooner (within 1 week) if eGFR is already <30 mL/min/1.73 m² or baseline potassium is >4.5 mEq/L. 1

Common Pitfall to Avoid

• The most common error is prematurely discontinuing ACE/ARB in advanced CKD (eGFR 15-29 mL/min/1.73 m²) out of fear of worsening kidney function. 5
• A multicenter Italian study found that patients with eGFR ≤29 mL/min/1.73 m² had 54% lower probability of continuing ACE/ARB compared to those with eGFR 30-59 mL/min/1.73 m², despite guideline recommendations to continue therapy. 5
• This practice removes cardiovascular and renal protection without evidence of benefit. 2, 5

Dosing Strategy in Advanced CKD

• Use the highest approved dose that is tolerated, even in advanced CKD, because proven benefits in clinical trials were achieved at target doses. 1
• There is no serum creatinine level per se that contraindicates ACE/ARB use. 1