What are the risks of Acute Interstitial Nephritis (AIN) in patients taking Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen (Advil) or naproxen (Aleve) for an extended period?

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Last updated: June 2, 2025View editorial policy

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From the Guidelines

Patients taking Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen (Advil) or naproxen (Aleve) for an extended period, such as a year, are at a significant risk of developing Acute Interstitial Nephritis (AIN), with the risk increasing with higher doses and longer duration of use. The risk of AIN is higher in elderly patients, those with existing kidney problems, and individuals taking multiple medications 1. According to the 2014 study published in the American Journal of Kidney Diseases, prolonged therapy with NSAIDs is not recommended in people with a Glomerular Filtration Rate (GFR) < 60 ml/min/1.73 m2, and they should be avoided in people with GFR < 30 ml/min/1.73 m2 1.

Key Points to Consider

  • NSAIDs can cause AIN by triggering immune-mediated hypersensitivity reactions in the kidneys
  • The risk of AIN increases with higher doses and longer duration of NSAID use
  • Patients with pre-existing kidney disease, congestive heart failure, or cirrhosis are at higher risk of developing renal complications from NSAID use 1
  • Alternative pain management strategies should be considered for patients at high risk of AIN
  • Patients taking NSAIDs long-term should have their kidney function monitored regularly and stay well-hydrated to minimize the risk of AIN

Recommendations

  • Use the lowest effective dose of NSAIDs for the shortest possible time
  • Monitor kidney function regularly in patients taking NSAIDs long-term
  • Consider alternative pain management strategies for patients at high risk of AIN
  • Avoid NSAIDs in patients with GFR < 30 ml/min/1.73 m2 or those taking RAAS blocking agents 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Risks of Acute Interstitial Nephritis (AIN) with NSAIDs

The risks of developing Acute Interstitial Nephritis (AIN) in patients taking Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen or naproxen for an extended period are as follows:

  • Drug-induced acute interstitial nephritis (DI-AIN) occurs in 0.5%-3% of all kidney biopsies and in 5%-27% of biopsies performed for acute kidney injury 2.
  • NSAIDs are one of the most common causes of DI-AIN, with antibiotics being the most implicated class of medication, followed by proton pump inhibitors, nonsteroidal anti-inflammatory agents, and 5-aminosalicylates 2.
  • The incidence of DI-AIN appears to be increasing, particularly in the elderly, and identification of the offending agent may be complicated by polypharmacy 2.
  • Acute interstitial nephritis can follow the use of nearly all NSAIDs, but the number of reported cases is low, with most patients being elderly and developing a nephrotic syndrome with acute renal failure while taking NSAID for months 3.

Factors Influencing the Development of AIN

Several factors can influence the development of AIN in patients taking NSAIDs, including:

  • Duration of NSAID use: Patients taking NSAIDs for months or years may develop papillary necrosis, chronic interstitial nephritis, or even end-stage renal disease (ESRD) 3.
  • Age: Elderly patients are more susceptible to DI-AIN, and kidney biopsy is underused in this population 2.
  • Polypharmacy: The use of multiple medications can increase the risk of DI-AIN and make it more difficult to identify the offending agent 2.

Importance of Monitoring and Adherence

Regular monitoring and adherence to medication regimens are crucial in preventing and managing AIN:

  • Medication adherence is essential to ensure the full benefit of treatment and prevent non-adherence, which can be costly for the health service 4.
  • Healthcare professionals play a vital role in promoting adherence and understanding the reasons for non-adherence 4.

References

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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