Does Angiotensin Receptor Blocker (ARB) worsen Acute Kidney Injury (AKI)?

From the Guidelines

Angiotensin receptor blockers (ARBs) should not be discontinued for minor increases in serum creatinine (<30%) in the absence of volume depletion, as they can provide benefits in slowing kidney disease progression and reducing mortality, according to the most recent evidence 1. When considering the use of ARBs in patients with or at risk of acute kidney injury (AKI), it is essential to weigh the potential benefits against the risks. The latest guidelines suggest that elevations in serum creatinine up to 30% from baseline with renin-angiotensin system (RAS) blockers, such as ARBs, should not be confused with AKI 1. Key points to consider:

• ARBs can potentially worsen AKI in certain clinical situations, such as volume depletion, hypotension, or sepsis 1.
• Patients with bilateral renal artery stenosis, severe heart failure, or those taking other medications that affect kidney function are at higher risk 1.
• Kidney function should be monitored with serum creatinine and potassium measurements when starting ARBs and during acute illness 1.
• Once the patient is hemodynamically stable and kidney function is recovering, ARBs can often be safely reintroduced, usually starting at lower doses with careful monitoring 1. The most recent and highest quality study 1 supports the continued use of ARBs in patients with minor increases in serum creatinine, emphasizing the importance of careful monitoring and individualized treatment decisions.

From the FDA Drug Label

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2. 2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group In patients with heart failure, candesartan cilexetil and hydrochlorothiazide tablets may cause excessive hypotension, which may lead to oliguria, azotemia, and (rarely) with acute renal failure and death Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics.

Angiotensin II Receptor Blockers (ARBs), such as losartan, valsartan, and candesartan, may worsen acute kidney injury (AKI) in certain patients, particularly those with:

• Pre-existing renal impairment
• Volume depletion
• Heart failure
• Diabetes
• Those taking NSAIDs or other agents that affect the renin-angiotensin system It is essential to closely monitor renal function and electrolytes in patients taking ARBs, especially when used in combination with other medications that may increase the risk of AKI 2, 3, 4.

From the Research

Angiotensin Receptor Blockers (ARBs) and Acute Kidney Injury (AKI)

• The impact of ARBs on AKI is a topic of ongoing research, with studies yielding mixed results 5, 6, 7, 8.
• A systematic review and meta-analysis found that exposure to ACEi/ARB after AKI onset is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD 5.
• Another study found that ACEI or ARB use after AKI is associated with lower mortality, but a higher risk of hospitalization for a renal cause 6.
• A single-center observational study found that the risk of AKI in emergency medical admissions is higher among users of ACEIs/ARBs at target or above target dosages 7.
• A study analyzing the impact of different ACEI or ARB resumption timing on post-AKI outcomes found that earlier resumption is associated with lower mortality, MACCE, and new dialysis initiation or ESRD, without increased risks of severe hyperkalemia and re-AKI admissions 8.

Key Findings

• The use of ARBs after AKI may be associated with lower mortality and reduced risk of recurrent AKI, but may also increase the risk of hospitalization for a renal cause 5, 6.
• The risk of AKI is higher among users of ACEIs/ARBs at target or above target dosages, suggesting the need for careful dosing and monitoring 7.
• Early resumption of ACEI/ARB after AKI may be beneficial, with lower risks of mortality, cardiovascular events, and ESRD, without heightened risks of severe hyperkalemia or rehospitalization for AKI 8.

Considerations for Clinical Practice

• Clinicians should carefully consider the potential benefits and risks of ARB use in patients with AKI, taking into account individual patient factors and comorbidities 5, 6, 7, 8.
• Close monitoring of renal function and electrolyte levels is essential in patients with AKI who are using ARBs, particularly at high dosages 7.
• Further research is needed to fully understand the impact of ARBs on AKI and to inform evidence-based clinical practice guidelines 5, 6, 7, 8, 9.