What is the approach to using Angiotensin Receptor Blockers (ARBs) in a patient with Chronic Kidney Disease (CKD) and severely impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 4?

ARB Use in CKD with eGFR of 4

Primary Recommendation

Consider reducing the dose or discontinuing the ARB in this patient with eGFR of 4 mL/min/1.73 m², particularly if there are uremic symptoms, uncontrolled hyperkalemia despite medical management, or symptomatic hypotension. 1

Clinical Context and Decision Framework

When to Continue ARB at eGFR 4

• Continue ARB therapy if the patient is tolerating it well (no symptomatic hypotension, manageable potassium levels, no severe uremic symptoms) because the guideline explicitly states to continue ACE inhibitors or ARBs even when eGFR falls below 30 mL/min/1.73 m². 1

• The cardiovascular and renal protective benefits may still outweigh risks in stable patients without contraindications, as KDIGO recommends continuation through advanced CKD stages. 1

When to Reduce Dose or Discontinue ARB at eGFR 4

Discontinue or reduce the ARB dose in the following specific situations:

• Uremic symptoms are present (nausea, vomiting, altered mental status, pruritus) that may be ameliorated by stopping the ARB, as this is explicitly mentioned as a reason to consider discontinuation when eGFR <15 mL/min/1.73 m². 1

• Uncontrolled hyperkalemia persists despite implementing potassium-lowering measures (dietary restriction, diuretics, potassium binders), as hyperkalemia management should be attempted first before stopping the ARB. 1

• Symptomatic hypotension occurs with systolic blood pressure ≤90 mm Hg or symptoms of dizziness, syncope, or presyncope. 1, 2

• Acute intercurrent illness develops that increases AKI risk (severe infection, dehydration, contrast exposure), as KDIGO recommends temporary discontinuation of renin-angiotensin-aldosterone system blockers during serious illness in patients with eGFR <60 mL/min/1.73 m². 1

Critical Monitoring Parameters

Before Making the Decision

• Check serum potassium immediately - if >5.5 mEq/L, implement potassium-lowering strategies first (stop potassium supplements, dietary restriction, add or increase loop diuretics, consider potassium binders) rather than immediately stopping the ARB. 1

• Assess blood pressure - document whether patient has symptomatic hypotension or asymptomatic low readings. 1

• Evaluate for uremic symptoms - specifically ask about nausea, vomiting, altered mental status, pruritus, anorexia, and metallic taste. 3

• Review recent creatinine trends - if creatinine rose >30% within 4 weeks of ARB initiation or dose increase, this is a specific indication to discontinue. 1

If Continuing ARB

• Monitor potassium and creatinine every 1-2 weeks initially given the extremely low eGFR, then monthly once stable. 1

• Avoid all potassium supplements and potassium-based salt substitutes, and counsel on limiting high-potassium foods. 1

• Never combine with ACE inhibitors or direct renin inhibitors - dual RAS blockade is contraindicated and increases risks of hyperkalemia, hypotension, and acute kidney injury. 1, 4

Practical Considerations at eGFR 4

Kidney Replacement Therapy Planning

• If the patient is approaching or planning for dialysis initiation, continuing the ARB may provide cardiovascular protection during the transition period, unless contraindications exist. 1

• Once dialysis is initiated, the decision to continue ARB should be reassessed based on blood pressure control needs and potassium management on dialysis. 1

Drug-Specific Considerations

• ARBs are generally safer than ACE inhibitors regarding hyperkalemia risk in advanced CKD, though both carry similar risks. 4

• Losartan specifically requires monitoring for lithium interactions if the patient is on lithium, as ARBs increase lithium levels. 4

• Avoid NSAIDs completely as coadministration with ARBs in advanced CKD significantly increases acute kidney injury risk. 1, 3, 4

Common Pitfalls to Avoid

• Do not automatically discontinue ARB based solely on eGFR of 4 - the decision must be based on clinical tolerance, not just the number. 1

• Do not stop ARB for asymptomatic mild hyperkalemia (5.0-5.5 mEq/L) without first attempting potassium-lowering measures. 1

• Do not continue ARB if creatinine rose >30% within 4 weeks of starting or increasing the dose, as this indicates hemodynamic intolerance beyond expected changes. 1

• Do not use ARB in combination with ACE inhibitors or aliskiren - the VA NEPHRON-D trial showed increased hyperkalemia and acute kidney injury without additional benefit. 4

Complementary Therapies at eGFR 4

• SGLT2 inhibitors are generally not initiated at eGFR <20 mL/min/1.73 m², but if already on one, it can be continued until dialysis initiation. 1

• Nonsteroidal MRAs (finerenone) are contraindicated at eGFR <25 mL/min/1.73 m² and should not be used at this level of kidney function. 1

• Statin therapy should be continued or initiated for cardiovascular protection in patients ≥50 years with eGFR <60 mL/min/1.73 m². 3

Evidence Quality Note

The recommendations for ARB continuation at very low eGFR levels are based on practice points and expert opinion rather than randomized controlled trial data, as most major trials excluded patients with eGFR <30 mL/min/1.73 m². 1, 5 The STOP ACEi trial is ongoing to provide definitive evidence on this question. 5 In the absence of strong trial data, the decision at eGFR 4 should prioritize patient safety - specifically avoiding hyperkalemia, hypotension, and uremic symptoms - while recognizing potential cardiovascular benefits if the drug is tolerated.