Letters to the Editor

Acute interstitial nephritis due to omeprazole

Widely regarded as safe and effective, PPIs are among the most commonly used medications in the world today. However, a spate of observational studies suggest an association between PPI use and adverse events, including infection, bone fracture, and dementia. This review details evidence linking the use of PPI therapy to the development of kidney disease, including early case reports of acute interstitial nephritis and subsequent large observational studies of AKI, CKD, and ESRD. The majority of studies showed higher risk of kidney outcomes among persons prescribed PPI medications, with effect sizes that were slightly higher for AKI (∼2- to 3-fold) compared with CKD and ESRD (1.2- to 1.8-fold). Although observational pharmacoepidemiology studies are limited by the possibility of residual confounding and confounding by indication, many of the described studies conducted rigorous sensitivity analyses aimed at minimizing these biases, including new-user design, comparison to similar agents (e.g., histamine₂ receptor antagonists), and evaluation for a dose response, with robust results. Given the widespread use of PPIs, even a small effect on kidney outcomes could result in large public health burden. Timely cessation of PPI therapy when there is no clear indication for use might reduce the population burden of kidney disease.

Background & Aims: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF). The aim of this study was to investigate how widespread this complication is in Australia, to identify which PPIs are implicated, and to establish whether PPI-induced AIN is a class effect. Methods: We undertook a retrospective case review of potential cases at 2 teaching hospitals and a review of registry data from the Therapeutic Goods Administration of Australia (TGA). Parameters sought included the drug implicated, concurrent medications, symptoms, signs, serum creatinine, and time of onset after prescription. Results: We identified 18 cases of biopsy-proven PPI-induced AIN causing ARF in the retrospective case review, which is the largest hospital-based case series to date. The TGA registry data identified an additional 31 cases of “biopsy proven interstitial nephritis.” An additional 10 cases of “suspected interstitial nephritis,” 20 cases of “unclassified acute renal failure,” and 26 cases of “renal impairment” were also identified. All 5 commercially available PPIs were implicated in these cases. Conclusion: With the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect. Failure to recognize this entity might have catastrophic long-term consequences including chronic kidney disease. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.

Omeprazole is a proton pump inhibitor that is used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Thus far, 17 cases of acute interstitial nephritis (AIN) secondary to omeprazole have been described. Another case of AIN is described in a 36-yr-old woman presenting with nausea, vomiting, weight loss, and a rising serum creatinine concentration. Omeprazole therapy had ceased 2 wk before admission. AIN was diagnosed by renal biopsy and corticosteroid therapy was initiated. After 4 wk of therapy the serum creatinine concentration had normalized. Among the reported cases in the literature, AIN was diagnosed after an average of 2.7 months of therapy with 20–40 mg of omeprazole daily. Recurrence was universal on rechallenge. Common symptoms included fatigue, fever, anorexia, and nausea. The classic triad of fever, rash, and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, pyuria, eosinophilia, and anemia. Management consisted of withdrawal of omeprazole and corticosteroid therapy in some patients. All but one patient recovered normal renal function. Corticosteroid therapy was well tolerated and may have been beneficial.

Omeprazole is a proton pump inhibitor widely used in the treatment of gastro-esophageal reflux disease and peptic ulcer disease. In a 73-year-old man we describe renal failure due to acute interstitial nephritis after use of omeprazol during 4 months. Unexpected renal failure without signs of hydronephrosis should always provoke awareness of drug reaction, omeprazole being one of the possible drugs.