Which class offers more renal protection, Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin Receptor Blockers (ARBs)?

ACEIs and ARBs Offer Equivalent Renal Protection

Both ACE inhibitors and ARBs provide equivalent renal protection in patients with diabetes and chronic kidney disease, and current guidelines do not distinguish between these two drug classes in terms of superiority for kidney outcomes. 1

Guideline-Based Equivalence

The most recent American Diabetes Association guidelines (2025) explicitly state that either ACEIs or ARBs should be used as first-line therapy for hypertension when albuminuria is present, without preferential recommendation of one class over the other. 1 This represents the consensus position across major guideline bodies, including the 2024 and 2022 ADA standards. 1

For patients with albuminuria (UACR ≥30 mg/g), either an ACE inhibitor or ARB at maximal tolerated doses is recommended as first-line therapy, with the choice between them based primarily on tolerability rather than efficacy differences. 1

Mechanism of Renal Protection

Both drug classes provide renal protection through similar mechanisms:

• Reduction of intraglomerular pressure by preferentially dilating efferent arterioles, which decreases glomerular capillary pressure and proteinuria independent of systemic blood pressure effects. 2, 3

• Decreased albuminuria and slowed GFR decline in patients with established CKD, particularly those with diabetes and macroalbuminuria. 2

• Reduced oxidative stress and decreased NLRP3 inflammasome activity in the kidney, contributing to their kidney-protective properties. 2

Clinical Evidence Supporting Equivalence

The landmark trials demonstrating renal protection have used both drug classes with similar outcomes:

• In the CREDENCE trial, canagliflozin was studied on background therapy where >99% of participants were already taking either an ACE inhibitor or ARB, demonstrating that both classes serve as appropriate foundation therapy. 1

• Guidelines consistently group ACEIs and ARBs together as "RAS inhibitors" when discussing renal protection strategies, reflecting their equivalent clinical utility. 1, 2

Algorithm for Drug Selection

When albuminuria is present (UACR ≥30 mg/g):

1. Initiate either an ACEI or ARB at standard starting dose. 1

2. Titrate to maximum tolerated dose indicated for blood pressure treatment, as clinical trials demonstrating efficacy used maximal dosing. 2, 4

3. If one class is not tolerated (e.g., ACE inhibitor-induced cough or angioedema), substitute with the other class. 1

4. Monitor serum creatinine/eGFR and potassium within 2-4 weeks of initiation or dose change, then at least annually. 1, 5

5. Accept up to 30% increase in serum creatinine without associated hyperkalemia, as this represents expected hemodynamic changes rather than harm. 5

When albuminuria is absent (UACR <30 mg/g):

• Neither ACEIs nor ARBs are superior to thiazide-like diuretics or dihydropyridine calcium channel blockers for cardioprotection or renal protection. 1, 5

• Do not prescribe ACEIs or ARBs solely for "renal protection" in diabetic patients without albuminuria or hypertension, as trials show no benefit and one trial demonstrated increased cardiovascular events. 5

Critical Pitfalls to Avoid

Never combine ACE inhibitors and ARBs. Multiple clinical trials have demonstrated higher adverse event rates (hyperkalemia and acute kidney injury) without additional benefits on cardiovascular or CKD outcomes compared to monotherapy. 1, 2, 5, 4

Do not underdose these medications. Concerns about rising serum creatinine often lead to suboptimal dosing, but clinical trials demonstrating efficacy used maximum tolerated doses. 2

Monitor for hyperkalemia risk, especially with:

• Coadministration with potassium-sparing diuretics, NSAIDs, or mineralocorticoid receptor antagonists. 1, 5
• Patients with reduced eGFR (<60 mL/min/1.73 m²). 1
• Check serum potassium frequently in high-risk patients. 5

Practical Considerations

ARBs may be preferred in specific clinical scenarios due to fewer side effects, particularly the absence of ACE inhibitor-induced cough, which affects 5-20% of patients. 6 However, this represents a tolerability advantage rather than superior renal protection. 6

Both drug classes can be continued even as kidney function declines to eGFR <30 mL/min/1.73 m², as they may provide cardiovascular benefit without significantly increasing the risk of end-stage kidney disease. 1, 4