Why are Angiotensin-Converting Enzyme (ACE) inhibitors protective for the kidneys?

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Last updated: March 12, 2025View editorial policy

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From the Guidelines

ACE inhibitors are protective for the kidneys because they reduce intraglomerular pressure and protein leakage while decreasing inflammation and fibrosis, as supported by the most recent and highest quality study 1. These medications work by blocking the conversion of angiotensin I to angiotensin II, which prevents vasoconstriction of the efferent arteriole in the kidney. This action lowers pressure within the glomerulus, reducing hyperfiltration that can damage kidney structures over time. Some key points to consider when using ACE inhibitors for kidney protection include:

  • They are particularly beneficial for patients with diabetes, hypertension, or existing kidney disease with proteinuria, as noted in 1 and 1.
  • Common ACE inhibitors used for kidney protection include lisinopril (10-40 mg daily), enalapril (5-40 mg daily), and ramipril (2.5-20 mg daily).
  • When starting ACE inhibitors, kidney function and potassium levels should be monitored, especially within 1-2 weeks of initiation, as recommended in 1.
  • These medications may cause a temporary decrease in glomerular filtration rate and increase in creatinine (up to 30%), which is generally acceptable if it stabilizes, as stated in 1.
  • Side effects can include dry cough, angioedema, hyperkalemia, and hypotension.
  • ACE inhibitors are often considered first-line therapy for hypertensive patients with chronic kidney disease due to their proven ability to slow disease progression beyond their blood pressure-lowering effects, as supported by 1 and 1. It's also important to note that the combined use of ACE inhibitors and ARBs should be avoided, as it has been found to have no benefits on CVD or CKD and has higher adverse event rates, as reported in 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Mechanisms of Renal Protection

  • ACE inhibitors reduce systemic vascular resistance, which accounts for their long-term renoprotective effects in patients with diabetic and non-diabetic renal disease 2
  • The fall in filtration pressure due to ACE inhibitors contributes to their antiproteinuric effect and long-term renoprotection 2
  • ACE inhibitors also have an antiproliferative effect, reduce proteinuria, and have a lipid-lowering effect in proteinuric patients 3, 4

Effects on Blood Pressure and Proteinuria

  • ACE inhibitors lower systemic blood pressure, reduce glomerular capillary pressure, and reduce proteinuria, which slows the progression of chronic renal failure 4, 5
  • Combining an ACE inhibitor with an angiotensin II receptor blocker reduces plasma and kidney tissue angiotensin II levels, which may provide additional renoprotection 6
  • Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d are associated with the lowest risk for kidney disease progression 5

Patient-Specific Considerations

  • Patients with heart failure, diabetes mellitus, and/or chronic renal failure are at the greatest risk for renal adverse effects, but also may expect the greatest benefit from ACE inhibitors 2, 3
  • Elderly patients with diabetes mellitus, coronary heart disease, or peripheral vascular occlusion are at risk for deterioration of kidney function due to renal artery stenosis 3
  • Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[ACE inhibitors and the kidney].

Wiener medizinische Wochenschrift (1946), 1996

Research

[ACE inhibitors and the kidney].

Wiener medizinische Wochenschrift (1946), 1996

Research

Effect of combining an ACE inhibitor and an angiotensin II receptor blocker on plasma and kidney tissue angiotensin II levels.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2002

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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