How are Angiotensin-Converting Enzyme (ACE) inhibitors handled in Acute Kidney Disease (AKD)?

From the Guidelines

ACE inhibitors should not be discontinued in patients with acute kidney disease (AKD) for minor increases in serum creatinine (<30%), in the absence of volume depletion, as the benefits of these medications often outweigh the risks 1. When considering the management of ACE inhibitors in AKD, it is essential to weigh the potential benefits against the risks. The primary concern with ACE inhibitors in AKD is their potential to worsen kidney function by reducing glomerular filtration pressure. However, recent evidence suggests that small elevations in serum creatinine (up to 30% from baseline) with renin-angiotensin system (RAS) blockers, such as ACE inhibitors, should not be confused with acute kidney injury (AKI) 1.

Key considerations in the management of ACE inhibitors in AKD include:

• The patient's underlying conditions and the original indication for ACE inhibitor therapy
• The presence of volume depletion, which may necessitate temporary discontinuation of ACE inhibitors
• The need for close monitoring of kidney function, typically by checking creatinine and potassium levels 1-2 weeks after restarting or dose adjustments
• The importance of not dosing ACE inhibitors at unnecessarily low levels due to fear of serum creatinine increases, as maximally tolerated doses are often required to achieve therapeutic benefits

In general, the decision to restart ACE inhibitors after AKI or AKD should be individualized, taking into account the patient's specific clinical context and the potential risks and benefits of therapy. The most recent and highest quality evidence suggests that ACE inhibitors can be safely continued in patients with AKD, even with minor increases in serum creatinine, as long as there is no associated hyperkalemia or volume depletion 1.

From the FDA Drug Label

In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin converting enzyme inhibitors, including enalapril maleate, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine were observed in 20 percent of patients. Evaluation of patients with hypertension or heart failure should always include assessment of renal function

Handling of ACE inhibitors in AKD (Acute Kidney Disease):

• Caution is advised when using ACE inhibitors, such as enalapril, in patients with impaired renal function or those at risk of developing renal impairment.
• Monitoring of renal function is recommended, especially during the first few weeks of therapy.
• Dosage reduction or discontinuation of the ACE inhibitor and/or diuretic may be necessary in patients who develop increases in blood urea and serum creatinine.
• Hyperkalemia is a potential risk, especially in patients with renal insufficiency, diabetes mellitus, or those using potassium-sparing diuretics or potassium supplements.
• Concomitant use of other agents that affect the renin-angiotensin system, such as angiotensin receptor blockers or aliskiren, should be avoided due to increased risks of hypotension, hyperkalemia, and changes in renal function 2 3.

From the Research

Handling of ACE Inhibitors in Acute Kidney Disease (AKD)

• The use of Angiotensin-Converting Enzyme Inhibitors (ACEi) or Angiotensin II Receptor Blockers (ARB) in patients with Acute Kidney Disease (AKD) has been studied to understand its impact on clinical outcomes 4.
• A systematic review and meta-analysis found that exposure to ACEi/ARB after AKI is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident Chronic Kidney Disease (CKD) 4.
• Another study found that acute exposure to ACEi/ARB during an episode of AKI was not associated with persistent AKD at the time of first clinic visit, suggesting that the receipt of such agents does not impede kidney recovery following AKI 5.
• Experts recommend that medication reconciliation should occur at admission and discharge, at AKD diagnosis and change in AKD phase, and when the patient's condition changes, and that strategies to avoid adverse drug reactions in AKD should seek to minimize adverse events from overdosing and nephrotoxicity 6.

Considerations for ACE Inhibitor Use in AKD

• The risk of hyperkalemia is higher in ACEi/ARB users than in nonusers, and patients with reduced Glomerular Filtration Rate (GFR) are at increased risk of hyperkalemia 4, 7.
• The use of ACEi/ARB in patients with early (stage 1 to 3) non-diabetic Chronic Kidney Disease (CKD) is uncertain, and the available evidence is of very low certainty and high risk of bias 8.
• Diabetes mellitus does not affect the incidence of hyperkalemia independent of GFR, but the presence of diabetes should be considered when using ACEi/ARB in patients with CKD 7.

Monitoring and Management

• A dynamic monitoring plan including repeated serial assessment of clinical features, utilization of renal diagnostic tests, and therapeutic drug monitoring should be used to guide medication regimen assessment 6.
• Drug management during different phases of AKD requires an individualized approach and frequent re-assessment 6.