From the Guidelines
Angiotensin-converting enzyme inhibitors (ACE-Is) are the preferred first-line agents for blood pressure treatment among people with diabetes, hypertension, and chronic kidney disease (CKD), as they have proven benefits for prevention of CKD progression, particularly in those with albuminuria ≥300 mg/g creatinine 1.
Mechanism of Action
ACE-Is help with CKD by reducing intraglomerular pressure and proteinuria, which slows disease progression. They block the conversion of angiotensin I to angiotensin II, causing efferent arteriole dilation in the kidney. This reduces glomerular hypertension and decreases protein leakage through the glomerular membrane.
Benefits and Recommendations
The benefits of ACE-Is in CKD patients include:
- Slowing disease progression
- Reducing proteinuria
- Providing kidney protection and blood pressure control
- Being particularly beneficial for CKD patients with proteinuria and/or diabetes The recommended dose of ACE-Is should be titrated to the highest tolerated dose within the recommended range, and patients should be monitored for potential side effects including hyperkalemia, acute kidney injury, and cough. Kidney function and potassium levels should be checked 1-2 weeks after initiation or dose changes.
Key Considerations
- ACE-Is are considered to have similar benefits and risks as ARBs, and either can be used as first-line therapy for CKD patients with diabetes and hypertension 1.
- In the setting of lower levels of albuminuria (30–299 mg/g creatinine), ACE inhibitor or ARB therapy at maximum tolerated doses has reduced progression to more advanced albuminuria and slowed CKD progression, but has not reduced progression to end-stage kidney disease (ESKD) 1.
- A blood pressure level <130/80 mmHg is recommended to reduce cardiovascular disease (CVD) mortality and slow CKD progression among all people with diabetes, with lower blood pressure goals considered based on individual anticipated benefits and risks 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Mechanism of ACE-I in CKD
- ACE inhibitors (ACE-I) are first-line therapy in patients with chronic kidney disease (CKD) because they can slow disease progression 2, 3.
- The main adverse effects of ACE inhibitors are hypotension, renal function impairment, and hyperkalemia, which follow from their interaction with renin-angiotensin-aldosterone system (RAAS)-activity and volume depletion 2.
- This interaction can be turned into clinical benefit and increase efficacy of ACE inhibitors by reduction in dietary sodium or adding diuretics 2.
Benefits of ACE-I in CKD
- ACE-I and angiotensin receptor blockers (ARB) have beneficial effects on kidney outcomes and survival in people with a wide range of severity of kidney impairment 3, 4.
- ACE-I may make little or no difference to death, total cardiovascular events, cardiovascular-related death, stroke, myocardial infarction, and adverse events in patients with early CKD (stage 1 to 3) without diabetes mellitus (DM) 3.
- It is uncertain whether ACE-I reduces congestive heart failure, transient ischaemic attack, or proteinuria in patients with early CKD (stage 1 to 3) without DM due to the low certainty of the evidence 3.
Clinical Use of ACE-I in CKD
- Japanese guidelines recommend ACE-I and ARB as first-line therapy in hypertensive patients with CKD and proteinuria, but calcium channel blockers in patients with stage G4-5 CKD aged ≥75 years 5.
- Despite guideline recommendations, ACE-I and ARB are insufficiently prescribed for patients with hypertension associated with CKD with proteinuria 5.
- The prescription rate of ACE-I and ARB was lower in patients aged <75 years with CKD stage G1-G5 compared with patients aged ≥75 years old with CKD stage G1-G3 5.