Proton pump inhibitors identified as most common iatrogenic cause of acute interstitial nephritis

August 10, 2005

Aug 10, 2005

Singapore - Proton pump inhibitors (PPIs) have been identified as the most common iatrogenic cause of acute interstitial nephritis (AIN) seen in patients today, a new study suggests. Moreover, all five of the currently available PPIs have been implicated as potential causative agents of iatrogenic AIN in these findings, Australian researchers report.

"We had recognized that there was an association between omeprazole [Prilosec, Procter & Gamble] and this form of acute kidney failure, as we had a series of patients come in with the same pattern of acute kidney failure," Dr Simon Roger (University of Newcastle, Gosford, Australia) told renal wire in a later interview. "But we are now confident that this is a class effect rather than related to a specific PPI. And because PPIs are predominantly prescribed by family physicians, gastroenterologists, and surgeons, unless they are aware of a small but certain risk of acute renal failure, patients may end up with kidney failure and on dialysis."

PPIs are widely prescribed for the treatment of gastric disorders such as gastroesophageal reflux disease (GERD) and ulcers.

The results were presented at the International Society of Nephrology Third World Congress of Nephrology [ 1 ].

Three-pronged approach

Under lead author Dr Nimeshan Geevasinga (University of Sydney), the Australian group took a three-pronged approach to obtain prevalence data for potential PPI-induced AIN and renal failure. First, they retrospectively audited potential cases of PPI-associated AIN treated at two teaching hospitals, Westmead Hospital and Gosford Hospital, both in Australia. They also reviewed registry data from the Therapeutic Goods Administration (TGA) in Australia, the equivalent of the FDA in the US.

Finally, they reviewed the English literature for published accounts of PPI-associated AIN. From the hospital audit, the group identified 18 cases of PPI-induced AIN, "the largest-ever hospital-based case series," the authors note in their abstract. Their review of the TGA registry yielded another 31 cases of "biopsy-proven AIN," along with 10 cases of "suspected interstitial nephritis," 20 cases of "unclassified acute renal failure," and 26 cases of "renal impairment."

"From our hospital, registry data, and literature review, we have identified all five of the available PPIs as causative agents in AIN," investigators observe.

This is in contrast with other reports, in which omeprazole and lansoprazole [Prevacid, TAP Pharmaceutical Products] were singled out as the drugs most commonly associated with interstitial nephritis [ 2 ].

Proton pump receptors

As Roger noted, it is not fully understood how PPIs damage the kidney, but it is known that there are proton pump receptors within the kidney itself. Thus, "it could be that there is an allergic-type reaction in the kidney to a component of these drugs, and that may trigger an inflammatory response, which in turn may lead to kidney failure," he speculated. Certainly, with ever more widespread use of PPIs, "this adverse reaction is likely to become more prevalent," they note.

"Increased awareness will facilitate more rapid diagnosis and management of this potentially catastrophic event, which, if detected early, is eminently reversible," they add.

Roger also suggested that if patients become unwell "in any vague sort of way" following introduction of a PPI—often within twoto four months after starting therapy—physicians should maintain a high index of suspicion and ensure patients have their kidney function evaluated to detect potential PPI-induced AIN at the earliest possible stage.


  1. Geevasinga N, Coleman P, Roger S. Proton pump inhibitors: the most common iatrogenic cause of acute interstitial nephritis? Third World Congress of Nephrology; June 26-30, 2005; Singapore. Abstract FC-60015.

  2. Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol Dial Transplant 2004; 19:1441-1446.



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