Is ibuprofen (Nonsteroidal Anti-Inflammatory Drug, NSAID) suitable for patients with Impaired Renal Function?

From the Guidelines

Ibuprofen is not suitable for patients with impaired renal function, as it can worsen kidney function and potentially cause acute kidney injury. Patients with renal impairment should avoid ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) because these medications reduce blood flow to the kidneys by inhibiting prostaglandins that help maintain kidney perfusion 1. The 2020 VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis recommends avoiding NSAIDs in patients with eGFR <30 ml/min per 1.73 m2 1.

Key Considerations

• NSAIDs, including ibuprofen, should be avoided in patients with chronic kidney disease (CKD) or those at risk for cardiovascular disease (CVD) and serious upper gastrointestinal (UGI) toxicity 1.
• Assessment of renal function should occur before initiating NSAID therapy, and alternative pain management options should be considered for patients with impaired renal function 1.
• Acetaminophen (Tylenol) is typically a safer alternative for pain relief in patients with kidney disease, at recommended doses (up to 3000 mg daily in divided doses for adults with normal liver function) 1.

Alternative Pain Management Options

• Consultation with a nephrologist or healthcare provider is essential to determine appropriate medication options for patients with complex pain management needs 1.
• Patients with kidney disease should always inform all healthcare providers about their condition before taking any over-the-counter pain medications, as even short-term use of ibuprofen can potentially cause significant kidney damage in vulnerable individuals 1.

Supporting Evidence

The evidence from the 2020 VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip & Knee Osteoarthritis 1 and other studies 2, 3 supports the recommendation to avoid NSAIDs, including ibuprofen, in patients with impaired renal function. However, the most recent and highest quality study, 1, is prioritized in making this recommendation.

From the FDA Drug Label

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly Advanced Renal Disease No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Therefore, treatment with ibuprofen tablets is not recommended in these patients with advanced renal disease If ibuprofen tablets therapy must be initiated, close monitoring of the patients renal function is advisable.

Ibuprofen is not suitable for patients with impaired renal function due to the risk of renal toxicity and renal decompensation. The use of ibuprofen tablets is not recommended in patients with advanced renal disease. If ibuprofen therapy must be initiated, close monitoring of the patient's renal function is advisable 4.

From the Research

Ibuprofen and Impaired Renal Function

• Ibuprofen, a Nonsteroidal Anti-Inflammatory Drug (NSAID), can induce serious renal adverse effects in patients with risk factors, including impaired renal function 5.
• The adverse effects of NSAIDs on renal function are dose and duration-dependent, and can include sodium and water retention, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, and chronic kidney disease 5.
• Patients with impaired renal function should have preventative strategies in place when taking NSAIDs, including the use of the "lowest effective dose" for the "shortest possible time" and monitoring renal function, fluid retention, and electrolyte abnormalities 5.

Risk of Renal Injury with Ibuprofen

• Ibuprofen can cause renal damage, including functional acute renal failure, water and electrolyte disorders, and interstitial nephritis, although the risk is generally low at recommended dosages 6.
• Renal side-effects of ibuprofen are almost exclusively encountered in patients with low intravascular volume and low cardiac output, particularly in older adults 6.
• Alternative analgesic and antipyretic agents may display similar risks for renal injury as ibuprofen 6.

Pain Management in Patients with Impaired Renal Function

• NSAIDs, including ibuprofen, may be used in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) for short durations with careful monitoring 7.
• Nonopioid analgesics, such as acetaminophen and topical analgesics, are recommended as first-line treatments for pain management in patients with CKD and ESKD 7.
• Opioid use should be minimized and reserved for patients who have failed other therapies, due to the increased risk of adverse events in this population 7.

Incidence of Ibuprofen-Associated Renal Impairment

• The incidence of ibuprofen-associated renal impairment has been reported to be around 18% in a large general internal medicine practice 8.
• Independent predictors of renal impairment include age, prior renal insufficiency, coronary artery disease, male gender, elevated systolic blood pressure, and diuretic use 8.
• Elderly patients and patients with coronary artery disease are at increased risk for ibuprofen-associated renal impairment and should have their renal function monitored when taking ibuprofen 8.

Non-Steroidal Anti-Inflammatory Drugs and Renal Function

• The use of NSAIDs is associated with a range of renal effects, including interference with fluid and electrolyte homoeostasis, and can cause reversible renal insufficiency, interstitial nephritis, and papillary necrosis 9.
• NSAID-induced haemodynamic renal failure is virtually always reversible with appropriate management, while the relatively rare complications of interstitial nephritis and papillary necrosis are more often irreversible 9.
• The use of a prostaglandin E1 (PGE1) analogue has been suggested to prevent some of the adverse renal effects of NSAIDs in patients at high risk 9.