ASK DIS: 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:

ASK DIS