What are the recommendations for using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in patients with pre-existing kidney disease?

From the Guidelines

NSAIDs should be avoided in patients with pre-existing kidney disease due to their potential to worsen renal function, as evidenced by the American Family Physician study 1. If absolutely necessary, they should be used at the lowest effective dose for the shortest possible duration, with close monitoring of kidney function. The American College of Rheumatology 2012 recommendations suggest that oral NSAIDs should not be used in patients with chronic kidney disease stage IV or V, and the decision to use an oral NSAID in patients with chronic kidney disease stage III should be made on an individual basis after consideration of the benefits and risks 1. Common NSAIDs to avoid include ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac, and celecoxib (Celebrex). For pain management in these patients, acetaminophen (Tylenol) is typically the preferred first-line analgesic as it has minimal effects on kidney function. Key considerations for NSAID use in patients with kidney disease include:

• Close monitoring of serum creatinine, blood pressure, and assessment for fluid retention
• Avoidance of NSAIDs in patients with chronic kidney disease, heart failure, cirrhosis, or those taking diuretics or ACE inhibitors/ARBs
• Use of the lowest effective dose for the shortest possible duration
• Consultation with a nephrologist for stronger pain control or complex cases. The reason NSAIDs pose a risk is that they inhibit prostaglandin synthesis, which normally helps maintain renal blood flow and glomerular filtration rate, and in compromised kidneys, this inhibition can lead to acute kidney injury, fluid retention, electrolyte disturbances, and worsening of hypertension 1.

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.

Recommendations for using NSAIDs in patients with pre-existing kidney disease:

• NSAIDs should be used with caution in patients with impaired renal function.
• Patients with advanced renal disease should not be treated with NSAIDs, including ibuprofen and naproxen, unless close monitoring of renal function is advisable.
• The use of NSAIDs may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation in patients with pre-existing kidney disease.
• Patients at greatest risk of renal toxicity are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.
• If NSAID therapy must be initiated, the lowest effective dose should be used for the shortest possible duration, and patients should be monitored for signs of worsening renal function 2, 3.

From the Research

Recommendations for NSAID Use in Patients with Pre-Existing Kidney Disease

• Patients with pre-existing kidney disease should use NSAIDs with caution, as they can induce serious renal adverse effects, including sodium and water retention, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, and chronic kidney disease 4.
• The use of NSAIDs in patients with chronic kidney disease (CKD) is challenging due to the risk of nephrotoxicity, and alternative classes of analgesics, such as opioids, have become more commonly used for pain control in this population 5.
• However, opioids and other non-NSAID alternatives also come with significant risks, and the use of NSAIDs in patients with CKD should be considered on an individualized basis, taking into account the risk factors and comorbid conditions 6.

Preventative Strategies

• Patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention, and electrolyte abnormalities 4.
• Dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies, and use of calcium channel blockers for treating hypertension are also recommended as preventive measures 4.
• Before starting NSAID treatment, blood pressure should be measured, and unrecognised CKD should be screened in high-risk cases 7.

Monitoring and Contraindications

• Blood pressure and renal function should be monitored in most cases, especially in patients with pre-existing hypertension or CKD 7.
• The combination of NSAIDs and angiotensin inhibitors should be avoided, and empirical addition (or increase in the dose) of an antihypertensive agent of a different class should be considered in patients with pre-existing hypertension receiving renin-angiotensin system blockers 7.
• NSAIDs should be avoided in patients with treatment-resistant hypertension, high risk of cardiovascular disease, and severe CKD 7.