From the Guidelines
ACE inhibitors can accumulate in patients with Chronic Kidney Disease (CKD), potentially leading to increased bradykinin levels, and dosage adjustments are necessary to prevent excessive accumulation while maintaining therapeutic benefits. In patients with CKD, decreased kidney function can result in reduced clearance of ACE inhibitors, causing them to accumulate in the body 1. This accumulation can lead to enhanced inhibition of bradykinin degradation, resulting in higher bradykinin levels. Elevated bradykinin can contribute to side effects such as persistent dry cough, angioedema, and hypotension. Key considerations for the use of ACE inhibitors in CKD patients include:
- Regular monitoring of kidney function
- Dosage adjustments for patients with moderate to severe kidney impairment (eGFR < 30 ml/min)
- Balancing the benefits of ACE inhibitors for blood pressure control and kidney protection with the potential risks of accumulation and side effects, as recommended by guidelines such as the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. Healthcare providers should carefully weigh these factors to optimize the use of ACE inhibitors in patients with CKD.
From the FDA Drug Label
ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of lisinopril remains to be elucidated The answer to whether Angiotensin-Converting Enzyme (ACE) inhibitors can accumulate in Chronic Kidney Disease (CKD) to inhibit the breakdown of bradykinins is not directly addressed in the provided drug label. However, it is mentioned that ACE is identical to kininase, an enzyme that degrades bradykinin.
- The label does not provide information on the accumulation of ACE inhibitors in CKD.
- It does not explicitly state the effect of ACE inhibitors on bradykinin levels in CKD patients. Therefore, based on the provided information, no conclusion can be drawn about the accumulation of ACE inhibitors in CKD and their effect on bradykinin breakdown 2.
From the Research
Angiotensin-Converting Enzyme (ACE) Inhibitors and Chronic Kidney Disease (CKD)
- ACE inhibitors are commonly used in the treatment of patients with CKD, as they have been shown to slow the progression of kidney disease and reduce the risk of cardiovascular events 3, 4, 5, 6.
- The use of ACE inhibitors in patients with CKD has been associated with a reduced risk of kidney events, cardiovascular events, and all-cause mortality 4, 5, 6.
- However, the use of ACE inhibitors can also increase the risk of hyperkalemia, cough, and hypotension 5, 6, 7.
Mechanism of Action
- ACE inhibitors work by blocking the conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor and stimulator of aldosterone secretion 3.
- This blockade leads to a decrease in blood pressure and a reduction in proteinuria, which can help to slow the progression of kidney disease 3, 5, 6.
- ACE inhibitors also have a role in inhibiting the breakdown of bradykinins, which are potent vasodilators and can help to reduce blood pressure 3.
Clinical Outcomes
- The use of ACE inhibitors in patients with CKD has been associated with improved clinical outcomes, including a reduced risk of kidney events, cardiovascular events, and all-cause mortality 4, 5, 6.
- A systematic review and meta-analysis found that the use of ACE inhibitors or angiotensin II receptor blockers (ARBs) in patients with acute kidney injury (AKI) was associated with a lower risk of all-cause mortality, recurrent AKI, and progression to incident CKD 7.
- However, the use of ACE inhibitors can also increase the risk of hyperkalemia, which requires close clinical monitoring 5, 6, 7.