What can cause Angiotensin-Converting Enzyme (ACE) inhibitor-induced nephropathy?

From the Guidelines

ACE inhibitor-induced nephropathy is primarily caused by hemodynamic changes in the kidney, particularly in patients with conditions that lead to renal hypoperfusion, such as systemic hypotension, high-grade bilateral renal artery stenosis, or severe volume depletion, as noted in the study by 1. The mechanism involves the blockade of angiotensin II formation, which normally helps maintain glomerular filtration pressure by constricting the efferent arteriole. When ACE inhibitors block this effect, there is dilation of the efferent arteriole, reducing intraglomerular pressure and potentially causing a significant drop in glomerular filtration rate. Some of the key causes of ACE inhibitor-induced nephropathy include:

• Systemic hypotension, which can lead to inadequate renal perfusion, as seen in patients with a mean arterial pressure (MAP) that falls below levels necessary for adequate renal perfusion 1
• High-grade bilateral renal artery stenosis or stenosis of a dominant or single kidney, which can lead to a dependence on angiotensin II to maintain glomerular filtration pressure 1
• Severe volume depletion, often due to diuretic use, which can exacerbate the effects of ACE inhibitors on renal hemodynamics 1
• Concurrent use of other medications like NSAIDs or cyclosporine, which can have vasoconstrictor effects and worsen renal function in the presence of ACE inhibitors 1
• Pre-existing chronic kidney disease, where the kidneys may be more susceptible to the hemodynamic effects of ACE inhibitors, as noted in the guidelines by 1. Patients typically present with elevated creatinine levels, hyperkalemia, and sometimes metabolic acidosis. The nephropathy is usually reversible upon discontinuation of the ACE inhibitor, though recovery may take days to weeks depending on the severity and duration of the insult. It is essential to monitor patients closely for signs of renal dysfunction when initiating ACE inhibitor therapy, especially in those with pre-existing kidney disease or other risk factors, as recommended by 1.

From the FDA Drug Label

Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan tablets.

ACE inhibitor-induced nephropathy can be caused by:

• Drugs that inhibit the renin-angiotensin system
• Diuretics It may occur in patients with:
• Renal artery stenosis
• Chronic kidney disease
• Severe congestive heart failure
• Volume depletion 2

From the Research

Causes of ACE Inhibitor-Induced Nephropathy

• Preexisting chronic renal insufficiency: Patients with preexisting chronic renal insufficiency are more likely to experience an early rise in serum creatinine levels after initiation of ACE inhibitor therapy 3.
• Heart failure: Patients with heart failure are at a higher risk of developing renal adverse effects, including acute renal failure, when treated with ACE inhibitors 4.
• Diabetes mellitus: ACE inhibitors can slow the progression of diabetic nephropathy, but patients with diabetes are also at a higher risk of developing renal adverse effects 5.
• Volume depletion: Patients with volume depletion, such as those with heart failure or dehydration, are at a higher risk of developing acute renal failure when treated with ACE inhibitors 4.
• Bilateral renal artery stenosis: Patients with bilateral renal artery stenosis are at a higher risk of developing acute renal failure when treated with ACE inhibitors 4.
• Concomitant use of diuretics: The concomitant use of diuretics can increase the risk of hyperkalemia in patients treated with ACE inhibitors 3.
• Concomitant use of NSAIDs: The concomitant use of NSAIDs can increase the risk of renal dysfunction in patients treated with ACE inhibitors, particularly in elderly patients 6.
• Sodium depletion: Sodium depletion can potentiate the systemic and renal hemodynamic effects of ACE inhibition, both beneficial and adverse 4.

Risk Factors for ACE Inhibitor-Induced Nephropathy

• Advanced age: Elderly patients are at a higher risk of developing renal adverse effects, including acute renal failure, when treated with ACE inhibitors 3, 6.
• Severity of renal impairment: Patients with more severe renal impairment are at a higher risk of developing renal adverse effects, including acute renal failure, when treated with ACE inhibitors 3.
• Presence of heart failure: Patients with heart failure are at a higher risk of developing renal adverse effects, including acute renal failure, when treated with ACE inhibitors 4.
• Presence of diabetes mellitus: Patients with diabetes mellitus are at a higher risk of developing renal adverse effects, including acute renal failure, when treated with ACE inhibitors 5.