What is the effect of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Chronic Kidney Disease (CKD)?

From the Guidelines

NSAIDs should be avoided in patients with chronic kidney disease (CKD) due to their potential to worsen kidney function, as evidenced by the most recent study 1. The use of NSAIDs in CKD patients can lead to acute kidney injury through various mechanisms, including reduced prostaglandin production, interstitial nephritis, and sodium and water retention, which can exacerbate hypertension and edema 1. Key considerations for CKD patients who must take NSAIDs include:

• Using the lowest effective dose for the shortest possible duration
• Close monitoring of kidney function
• Maintaining adequate hydration
• Avoiding combination of multiple NSAIDs
• Stopping the medication if symptoms such as decreased urine output, increased swelling, or unexplained weight gain occur Regular monitoring of serum creatinine and estimated glomerular filtration rate (eGFR) is crucial when NSAIDs are used in CKD patients, with checks recommended within 1-2 weeks of starting therapy 1. Alternatively, acetaminophen (Tylenol) can be used as a first-line analgesic instead of NSAIDs like ibuprofen (Advil, Motrin), naproxen (Aleve), or celecoxib (Celebrex) to minimize the risk of kidney damage in CKD patients. It is essential to note that the revised Beers criteria for potentially inappropriate medication use in older adults indicate moderate evidence to support NSAID avoidance in elderly patients with creatinine clearance <30 ml/min 1. In clinical practice, it is crucial to prioritize the safety and well-being of CKD patients by avoiding or minimizing the use of NSAIDs, as supported by the consensus report of the acute disease quality initiative (ADQI) 16 workgroup 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 prostoglandin 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 Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. 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.

The use of NSAIDs can have a negative effect on Chronic Kidney Disease (CKD) by:

• Causing renal papillary necrosis and other renal injury
• Reducing renal blood flow, which may precipitate overt renal decompensation
• Increasing the risk of renal decompensation in patients with impaired renal function, heart failure, liver dysfunction, and those taking diuretics and ACE inhibitors
• Requiring close monitoring of renal function in patients with advanced renal disease It is recommended to avoid the use of NSAIDs in patients with advanced renal disease unless the benefits outweigh the risks, and to monitor renal function closely if therapy is initiated 2.

From the Research

Effects of NSAIDs on Chronic Kidney Disease (CKD)

• The use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in patients with Chronic Kidney Disease (CKD) is associated with an increased risk of acute kidney injury, progressive loss of glomerular filtration rate, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension 3, 4.
• The risk of nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate 3.
• Regular NSAID use could be associated with an increased incidence of CKD, but the relation between NSAID use and CKD progression is less clear 5.
• Topical NSAIDs have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but are still associated with an increased risk of acute adverse kidney outcomes in CKD 6.
• Both systemic and topical NSAIDs are independently associated with acute adverse kidney outcomes, including incident acute kidney injury (AKI) and need for nephrology specialist consult 6.

Considerations for NSAID Use in CKD

• The management of pain in patients with CKD is challenging, and NSAIDs have long been regarded as dangerous for use in this population due to their risk for nephrotoxicity 3.
• Alternative classes of analgesics, including opioids, have become more commonly used for pain control in CKD patients, but these alternatives also pose significant risks 3, 4.
• The use of NSAIDs in CKD patients should be cautious and individualized, taking into account the patient's risk factors and characteristics of use 3, 4.
• Further study is needed to quantify the risk of NSAID use in CKD patients, particularly in dialysis-dependent patients 7.