Published: November 2000

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Omeprazole-induced interstitial nephritis

Information on this subject has been updated. Read the most recent information.

Prescriber Update 20: 11-13
November 2000

Dr Ruth Savage, Medical Assessor
Centre for Adverse Reactions Monitoring
P O Box 913, Dunedin

Acute renal impairment due to interstitial nephritis is a rare, difficult to diagnose, complication of omeprazole, a medicine which is now widely used in New Zealand. The presenting symptoms, which are associated with elevation of plasma creatinine, commonly include rash, arthralgia, malaise, fever, nausea, lethargy and weight loss. Patients presenting with these symptoms, with no other apparent cause, should be investigated by dipstick examination and microscopy of urine and assessment of renal function. If either urinary or renal findings or both are abnormal, omeprazole should be withdrawn pending nephrology assessment. Patients usually respond rapidly to discontinuation of omeprazole, but full recovery of renal function may take 2-3 months, or, occasionally, even longer.

Interstitial nephritis is rare with omeprazole

Acute renal impairment caused by interstitial nephritis is a rare complication of treatment with omeprazole, a medicine which is now widely used in New Zealand. The first publication of a report of omeprazole-related interstitial nephritis was in 1992.¹ The New Zealand Centre for Adverse Reaction Monitoring (CARM) has received 7 reports of acute renal failure due to interstitial nephritis associated with omeprazole. While omeprazole was being monitored on the Intensive Medicines Monitoring Programme (IMMP), 2 reports of interstitial nephritis were received from a total cohort of 22,050 patients. There were several other reports of renal failure.

Symptoms of interstitial nephritis are non-specific

Recognition of interstitial nephritis may be difficult because the symptoms of renal impairment are non-specific. The identification of disturbance in renal function can only be made by carrying out biochemical tests.

In general the presenting features described for this disorder are fever, rash and eosinophilia but these features are not always seen. An analysis of 13 published reports² demonstrated that patients with interstitial nephritis involving omeprazole commonly presented with malaise, fever, nausea, lethargy and weight loss. The cases reported to CARM displayed similar symptoms. In one of the CARM cases, the woman was non-specifically unwell for several months before the diagnosis was made and omeprazole discontinued. Polyuria and, in one instance, polydipsia were other presenting features.

Urine microscopy may show white cells including eosinophils, white cell casts and few red cells, but may be unremarkable.³ Urinary eosinophils are only rarely found and require special stains for their identification. Plasma creatinine and urea concentrations will usually be elevated. The diagnosis can be confirmed by renal biopsy.

Interstitial nephritis may be caused by a medicine, an infection, or autoimmunity

Interstitial nephritis may be caused by infection, autoimmunity and glomerular disease as well as hypersensitivity to medicines.³ A large number of medicines are reported to have caused various forms of acute interstitial nephritis. The two therapeutic groups most commonly implicated are antibacterials, and nonsteroidal anti-inflammatory agents. The medicines most commonly implicated are methicillin, penicillin, sulphonamides, co-trimoxazole, cephalosporins, rifampicin, fenoprofen, mefenamic acid, allopurinol, phenytoin and thiazides.⁴ It is therefore difficult to assess the cause of interstitial nephritis in any given case. The identification of cause may be further confounded by corticosteroid therapy being initiated at the same time as the suspect medicine is withdrawn.

Interstitial nephritis with omeprazole responds to treatment withdrawal

In 13 published case reports, symptoms occurred between 2 weeks and 6 months after omeprazole was commenced.² In 2 possible cases reported to CARM, the duration of therapy was around 18 months. Doses have been within the recommended range of 20mg or 40mg daily. In 4 of the published cases, the patients responded to withdrawal of omeprazole alone, but 6 other patients also received corticosteroid therapy. Some, including one of the cases reported to CARM, responded to corticosteroid therapy but did not fully recover until omeprazole was withdrawn. Initial recovery after omeprazole was withdrawn was usually rapid over a few days although full recovery of renal function took up to 2 to 3 months, and even longer in rare cases. There are no known reports of death as a result of this adverse reaction. In 4 of the published cases, renal function deteriorated again when omeprazole was reintroduced.

Investigate patients for renal function and by urine microscopy

Patients taking omeprazole, or any of the medicines listed above, who present with symptoms and signs of hypersensitivity, for example, rash, fever, eosinophilia, arthralgia, or who are non-specifically unwell should have urine microscopy and an assessment of renal function. If either or both are abnormal, omeprazole, or other possible causative agents, should be withdrawn pending nephrology assessment.

References

1. Ruffenach S, Siskind MS, Lien Y-H H. Acute interstitial nephritis due to omeprazole. Am J Med 1992;93:472-473.
2. Yip D, Jardine M, Findlay M. Omeprazole-induced interstitial nephritis. J Clin Gastroenterology 1997;25(2):450-452.
3. Geetha D. Omeprazole-induced acute interstitial nephritis. Am J Gastro-enterology 1999;94:3375-3376
4. Swanepoel CR, Cassidy MJD. Renal Disorders. In Davies DM, Ferner, RE, de Glanville H. Textbook of Adverse Drug Reactions pp349-350. Chapman & Hall Medical, 1998.