What is the management of acute interstitial nephritis (AIN) caused by Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen and antibiotics?

From the Guidelines

The management of acute interstitial nephritis (AIN) caused by NSAIDs or antibiotics primarily involves immediate discontinuation of the offending drug, supportive care, and consideration of corticosteroid therapy. The first and most crucial step is to identify and stop the causative medication, whether it's ibuprofen, naproxen, penicillins, cephalosporins, or other culprits, as emphasized by the consensus report of the acute disease quality initiative (ADQI) 16 workgroup 1. Supportive care includes maintaining fluid and electrolyte balance, avoiding further nephrotoxic agents, and monitoring kidney function through regular serum creatinine measurements.

Key Considerations

• Discontinuation of the offending drug is essential to prevent further kidney damage, as drugs account for 20% of community-acquired AKI episodes that result in hospitalization 1.
• Selection of a less nephrotoxic drug and/or avoidance of a nephrotoxin should be the goal in all phases of acute kidney disease (AKD) 1.
• Combining nephrotoxins can result in pharmacodynamic drug interactions, such as the ‘triple whammy’ of NSAIDs, diuretics, and ACE inhibitors or ARBs, which can increase the risk of developing AKI 1.

Treatment Approach

• For patients with severe AIN or those who don't improve after drug discontinuation, corticosteroid therapy may be considered, typically prednisone at 0.5-1 mg/kg/day (usually 40-60 mg daily) for 1-2 weeks, followed by a gradual taper over 4-6 weeks.
• In cases of significant kidney dysfunction, temporary dialysis may be required.
• Close monitoring of renal function is essential during recovery, with follow-up creatinine measurements at 1,3, and 6 months after the acute episode.

Prevention of Future Episodes

• 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.
• 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.

From the Research

Management of Acute Interstitial Nephritis (AIN) Caused by Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antibiotics

• The mainstay of treatment for drug-induced AIN is discontinuation of the offending drug 2, 3, 4, 5, 6.
• Early withdrawal of the culprit drug is crucial, as it can improve prognosis and reduce the risk of chronic kidney disease 2, 5, 6.
• Corticosteroid therapy may be beneficial in patients with drug-induced AIN, especially when treatment is initiated early in the course of the disease 3, 4, 5, 6.
• The use of steroids can lead to faster recovery of kidney function, more complete recovery with less chronic kidney disease, and reduced need for chronic dialysis 3.
• However, the benefits of corticosteroid therapy remain unproven, and recent studies have shown that prolonged treatment beyond 8 weeks does not further improve kidney function recovery 5.
• Kidney biopsy is required to make a firm diagnosis of AIN, as the symptoms are variable and often not specific 2, 4, 6.
• Identification and removal of the offending drug, along with early steroid administration, can improve the recovery of renal function and decrease the risk of chronic renal impairment 6.

Causes of Acute Interstitial Nephritis (AIN)

• Drug-induced AIN is the most common cause of AIN, accounting for 60-70% of cases 4.
• Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent offending agents 2, 6.
• Other drugs that can cause AIN include proton pump inhibitors, 5-aminosalicylates, diuretics, allopurinol, phenytoin, and H2 receptor antagonists 2.
• Chemotherapeutic agents are an under-recognized cause of AIN 2.

Pathogenesis of Acute Interstitial Nephritis (AIN)

• AIN is characterized by interstitial inflammation, tubulitis, edema, and in some cases, eventual interstitial fibrosis 4, 6.
• The pathogenesis of AIN is based on an immunologic reaction against endogenous nephritogenic antigens or exogenous antigens processed by tubular cells, with cell-mediated immunity having a major pathogenic role 6.
• The characteristic interstitial infiltrates are mostly composed of lymphocytes, macrophages, eosinophils, and plasma cells, and experience a rapid transformation into areas of interstitial fibrosis 6.