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Published:10 June 2015

Keeping it Renal: Drug-Induced Acute Interstitial Nephritis

Prescriber Update 36(2): 26-27
June 2015

Key Messages

  • Acute interstitial nephritis is an important cause of acute kidney injury.
  • Over two-thirds of acute interstitial nephritis cases are drug-induced.
  • Antibiotics, non-steroidal anti-inflammatory drugs and proton pump inhibitors are most frequently associated with drug-induced acute interstitial nephritis.
  • Rapid identification and withdrawal of the suspect medicine is the mainstay of treatment.

Background

Acute interstitial nephritis (AIN) is the third most common cause of acute kidney injury (AKI) after prerenal AKI and acute tubular necrosis1. Over two-thirds of AIN cases are drug-induced and infection-related AIN accounts for 5% to 10% of cases2.

Medicines that can cause AIN

Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are most frequently associated with drug-induced AIN2. The role of proton pump inhibitors (PPIs) has also been highlighted more recently3. Medicines most commonly associated with AIN are shown in Table 1.

Table 1: Medicines associated with acute interstitial nephritis1

Medicine class Examples
Antibiotics β-lactam antibiotics*, fluoroquinolones*, rifampicin*, sulphur-based medicines*, vancomycin, minocycline, ethambutol, erythromycin, chloramphenicol
Analgesics non-steroidal anti-inflammatory drugs* (eg, diclofenac), selective COX-2 inhibitors (eg, celecoxib)
Gastrointestinal medicines proton pump inhibitors* (eg, omeprazole), h2-receptor antagonists (eg, ranitidine)
Antiviral medicines aciclovir, abacavir, indinavir, atazanavir
Antiepileptic medicines phenytoin*, phenobarbital, carbamazepine
Other medicines allopurinol*, 5-aminosalicylates* (eg, mesalazine, sulfasalazine), captopril, interferon, ciclosporin, anti-angiogenesis medicines (tyrosine kinase inhibitors [eg, sunitinib]), diuretics (eg, furosemide)


*most common causative medicines

The average time period between starting the medicine and the appearance of renal manifestations is 10 days4. However, this time period can be as short as one day after some antibiotics or as long as several months with NSAIDs4.

For PPIs, the interval is most commonly 10 to11 weeks but this can vary between one week and nine months2.

Clinical Features

Clinical suspicion of AIN in patients with AKI usually relies on:2

Sterile pyuria and leucocyte casts are important clues for the diagnosis of AIN in patients with AKI2. An important number of cases have an oligosymptomatic presentation; the classical triad of rash, fever and eosinophilia are less commonly observed than was initially reported2.

The absence of hypersensitivity reactions and normal urinary sediment are important features to distinguish acute tubular necrosis from AIN2. AIN is difficult to diagnose. Ultimately, kidney biopsy is needed to confirm the diagnosis2.

Treatment

Rapid identification and withdrawal of the suspect medicine is the mainstay of treatment2.

Early treatment with corticosteroids (within the first five days) can reduce the amount of tubulointerstitial fibrosis that develops and avoid incomplete recovery of renal function1,2. However, the use of corticosteroids is still controversial and further studies are required to confirm their place in the treatment of drug-induced AIN2.

New Zealand Cases

The Centre for Adverse Reactions Monitoring (CARM) has received 189 case reports of AIN. However, some cases involve more than one suspect medicine.

The most common medicines reported were omeprazole, diclofenac, flucloxacillin and amoxicillin-containing medicines.

Average onset time of AIN following medicine initiation varied from within a few days to more than one year. This is consistent with onset times reported in the literature.

The suspect medicine was withdrawn in 170 of the 189 cases. Of these 170 cases, there was definite improvement in 108 and the result not known in 50. It is not known if treatment with corticosteroids occurred in any of the reported cases.

Healthcare professionals are encouraged to report any adverse events to medicines, including drug-induced AIN, to CARM. Reports may be submitted on paper or electronically (https://nzphvc.otago.ac.nz/report/).

References
  1. Perazella M. 2014. Diagnosing drug-induced AIN in the hospitalized patient: a challenge for the clinician. Clinical Nephrology 81(6): 381–388.
  2. Praga M, Sevillano A, Auñon P, et al. 2014. Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury. Nephrology, Dialysis, Transplantation doi: 10.1093/ndt/gfu326 (accessed 1 April 2015).
  3. Medsafe. 2011. Proton pump inhibitors and interstitial nephritis. Prescriber Update 32(3): 25. URL: www.medsafe.govt.nz/profs/PUArticles/ProtonPumpSept2011.htm (accessed 19 May 2015).
  4. Praga M, González E. 2010. Acute interstitial nephritis. Kidney International 77(11): 956–961.
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