Which is more stressful on the kidneys, Angiotensin-Converting Enzyme Inhibitors (ACE-I) or Angiotensin Receptor Blockers (ARB)?

From the Guidelines

ACE inhibitors are more stressful on the kidneys than Angiotensin Receptor Blockers (ARBs) due to their potential to increase serum creatinine levels, which may require strict monitoring, as noted in the European Heart Journal guidelines 1. When considering the impact of ACE inhibitors and ARBs on kidney stress, it's essential to weigh the benefits and risks of each medication class. Both classes have been shown to reduce microalbuminuria and progression towards end-stage renal dysfunction, but ACE inhibitors may cause an initial increase in serum creatinine levels, which typically returns to baseline in most patients 1. Key considerations for kidney stress include:

• The potential for ACE inhibitors to cause an increase in serum creatinine levels, particularly in patients with pre-existing renal dysfunction
• The need for strict monitoring of serum creatinine levels when initiating ACE inhibitors, as recommended in the guidelines 1
• The use of ARBs as an alternative to ACE inhibitors in patients with renal artery stenosis or other contraindications to ACE inhibitors
• The importance of monitoring kidney function in high-risk patients, including those with bilateral renal artery stenosis, severe dehydration, or those taking NSAIDs or diuretics concurrently. Overall, while both medication classes can affect kidney function, ACE inhibitors require closer monitoring due to their potential to increase serum creatinine levels, making them more stressful on the kidneys than ARBs 1.

From the Research

Comparison of ACE-I and ARB on Kidney Stress

• The effects of Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin Receptor Blockers (ARB) on kidney stress have been studied in various research papers 2, 3, 4, 5, 6.
• A systematic review and meta-analysis of randomized trials evaluating the combination of an ACE inhibitor and an ARB in patients with chronic proteinuric renal disease found that combination therapy resulted in a small, but significant, increase in serum potassium levels and a nonsignificant decrease in glomerular filtration rate 2.
• Another study found that the combination of ACE-inhibitor and ARB therapy in patients with chronic proteinuric renal disease is safe, without clinically meaningful changes in serum potassium levels or glomerular filtration rates, and is associated with a significant decrease in proteinuria 2.
• A network meta-analysis of randomized clinical trials found that ACEIs monotherapy significantly decreased the odds of kidney events, cardiovascular events, cardiovascular death, and all-cause death when compared to placebo, while ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than other antihypertensive drugs in all primary outcomes 4.
• A study on the pharmacokinetics and pharmacodynamics of angiotensin-receptor blockers in end-stage renal disease found that ARBs have a preferred pharmacokinetic profile with limited dialysability and minimal systemic accumulation, making them a favorable option for patients with end-stage renal disease 5.
• The STOP-ACEi trial found that discontinuing ACEi or ARB had similar effects on kidney outcomes, although discontinuation of ACEi appeared to have more unfavorable effects on kidney outcomes than stopping ARB 6.

Key Findings

• ACEIs and ARBs have different effects on kidney stress, with ACEIs having a higher risk of hyperkalaemia and cough, but also having a higher benefit for the prevention of kidney events, cardiovascular outcomes, cardiovascular death, and all-cause mortality 4.
• The combination of ACE-inhibitor and ARB therapy may be beneficial for patients with chronic proteinuric renal disease, but the safety and efficacy of this combination therapy need to be further established 2, 3.
• ARBs may be a favorable option for patients with end-stage renal disease due to their preferred pharmacokinetic profile 5.
• Discontinuing ACEi or ARB may have similar effects on kidney outcomes, but the decision to discontinue these medications should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 6.