Sunday, June 5, 2016

PPI and Interstitial Nephritis

Symptoms
  • Patients with acute interstitial nephritis can present with the non-specific symptoms consistent with acute renal failure.
  • Presenting symptoms include fever, rash, eosinophilia, malaise, myalgia, arthlargia, weight loss, altered urine output, blood or pus cells in the urine and/or high blood pressure.
  • In some cases symptoms may also mimic those of vasculitis.
  • A definitive diagnosis of interstitial nephritis can only be confirmed with renal biopsy.
  • If interstitial nephritis is suspected, urine microscopy and renal function should be assessed.
Drug Induced Nephritis
  • Over 100 drugs are known to trigger IN
  • Antibiotics (beta-lactams [cephalosporins and penicillins], quinolones [including ciprofloxacin and norfloxacin], sulphonamides [including co-trimoxazole], macrolides, isoniazid, rifampicin and vancomycin)
  • Non-steroidal anti-inflammatory drugs (almost all have been implicated)
  • Diuretics (particularly those with a sulphonamide moiety, such as furosemide and thiazides)
  • Allopurinol, calcium channel blockers, angiotensin-converting enzyme inhibitors (particularly captopril), carbamazepine, H2-antagonists, phenytoin, proton pump inhibitors, propylthiouracil and quinine
  • involvement of PPIs should be considered among a number of other risk factors. 
  • Other risk factors include: the presence of infection; and immune and neoplastic disorders.
Evidence for Causative Relationship
  • Interstitial nephritis may occur with all of the proton pump inhibitors, although most reports to the Australian Adverse Drug Reactions Advisory Committee (ADRAC) have been with omeprazole.
  • To date (14 May 2007) ADRAC have 82 reports associated with proton pump inhibitors.
  • Of these cases, 50 were associated with omeprazole, 12 with esomeprazole, 6 with pantoprazole and 14 with rabeprazole.
  • The duration of proton pump inhibitor treatment before presentation is usually between two weeks and nine months
Evidence Against Causative Relationship
  • findings partially reflect unmeasured confounders or intergroup differences in the baseline risk of acute renal outcomes
  • nonprescription medications that may have influenced the risk of acute renal outcomes, including over-the-counter NSAIDs
  • association between PPIs and acute kidney injury may be overstated given the low risk of recurrence following rechallenge
Management
  • Clinicians should maintain a high index of suspicion for acute interstitial nephritis among patients taking PPIs who present with a decline in renal function, particularly at the outset of treatment.
  • should prompt the physician to stop the drug
  • patient referred to a renal physician for further assessment or perform a renal biopsy if needed
  • Can start steroid therapy for halting a progressive renal disease
References:
  1. http://www.medsafe.govt.nz/profs/puarticles/protonpumpsept2011.htm
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741979/
  3. http://cmajopen.ca/content/3/2/E166.full
  4. http://www.australianprescriber.com/magazine/30/3/artid/884

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