What is Analgesic-Associated Nephropathy (AAN), also known as Analgesic Nephropathy?

From the Guidelines

The primary recommendation for managing analgesic nephropathy is immediate discontinuation of the offending medications, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), and switching to safer pain management alternatives such as acetaminophen (limited to less than 3g daily) 1.

Key Considerations

• Analgesic nephropathy is a form of chronic kidney disease caused by the prolonged and excessive use of pain medications, particularly those containing phenacetin, aspirin, and other NSAIDs.
• The condition develops gradually over years of regular analgesic use, typically requiring daily intake for at least 3-5 years.
• Patients should be educated to avoid taking NSAIDs (or any new medications) without consulting their nephrologist, and to use ACE inhibitors, decongestants, antivirals, antibiotics, and herbal products with caution 1.

Management and Prevention

• Kidney function should be monitored regularly through blood tests measuring creatinine and BUN levels, along with urinalysis to check for protein and blood.
• The disease process involves papillary necrosis and interstitial nephritis, where these medications damage the renal papillae and surrounding tissue, reducing blood flow to the kidneys and causing progressive scarring.
• Once established, the kidney damage is often irreversible, though stopping the medications can prevent further deterioration.
• Patients with analgesic nephropathy are also at increased risk for transitional cell carcinoma of the urinary tract, necessitating periodic screening.

Additional Recommendations

• Management focuses on controlling hypertension, treating urinary tract infections promptly, and implementing general kidney-protective measures including proper hydration and dietary modifications to slow progression to end-stage renal disease.
• Conventional analgesia, such as acetaminophen, should be used in dialysis patients with noninflammatory pain, and other drugs to consider are low-dose opiates and short courses of oral or intra-articular corticosteroids for acute inflammatory noninfectious arthritis 1.

From the Research

Definition and Causes of Analgesic Nephropathy

• Analgesic nephropathy is a clinical syndrome associated with the abuse of analgesic compounds, particularly those containing phenacetin and aspirin 2, 3, 4.
• The primary lesion in analgesic nephropathy is renal papillary necrosis (RPN), which is a nephrotoxic effect common to all nonsteroid antiinflammatory agents 3.
• Aspirin appears to be the major nephrotoxic agent, while phenacetin plays a secondary and synergistic role in the nephrotoxicity 2, 3, 4.

Clinical Symptoms and Diagnosis

• Analgesic nephropathy is characterized by poor clinical symptoms, with abnormal urinary findings being rare 4.
• The disease is usually discovered when advanced renal damage has occurred, with elevated serum creatinine, papillary necrosis, microhematuria, and renal colics 4.
• Diagnosis can be made precisely by the radiological demonstration of renal papillary necrosis 2.

Management and Prevention

• The most important aspect of management is the cessation of analgesic abuse, which leads to improvement and stabilization of renal function 2, 3, 4.
• Total avoidance of all non-steroid antiinflammatory agents is commonly associated with stabilization or improvement in renal function 2.
• Prevention can be achieved by high fluid intake and avoidance of more than 150 g phenacetin per year, or 0.5 g per day 4.
• Measures such as subjecting preparations containing phenacetin to prescription, restricting advertising, and providing detailed information about the kidney-damaging effects of phenacetin can help reduce phenacetin abuse 4.

Socio-Economic Importance and Current Understanding

• Analgesic nephropathy is a significant public health hazard, accounting for 10-20% of patients requiring recurrent dialysis in some countries 3, 4.
• The association between non-opioid analgesic agents and chronic kidney disease has long been suspected, with many clinicians accepting analgesic nephropathy as a real entity despite the paucity of scientific evidence 5.
• Recent reviews suggest that long-term ingestion of paracetamol and combination mixtures of aspirin and paracetamol may contribute to chronic renal impairment, but there is no convincing data to implicate non-steroidal anti-inflammatory drugs or aspirin monotherapy in the development of analgesic nephropathy 5.