A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use

Abstract

The magnitude of the suspected increase in risk of acute interstitial nephritis among proton pump inhibitor users is uncertain. Here, we conducted a nested case-control study using routinely collected national health and drug dispensing data in New Zealand to estimate the relative and absolute risks of acute interstitial nephritis resulting in hospitalization or death in users of proton pump inhibitors. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of proton pump inhibitor use between 2005 and 2009. Cases had a first diagnosis after cohort entry of acute interstitial nephritis confirmed by hospital discharge letter or death record, and renal histology (definite, 46 patients), or discharge letter or death record only (probable, 26 patients). Ten controls, matched by birth year and sex, were randomly selected for each case. In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (95% confidence interval) for current versus past use of proton pump inhibitors was 5.16 (2.21-12.05). The estimate was similar when all cases (definite and probable) and their corresponding controls were analyzed, and when potential confounders were added to the models. The crude incidence rates and confidence intervals per 100,000 person-years were 11.98 (9.11-15.47) and 1.68 (0.91-2.86) for current and past use, respectively. Thus, current use of a proton pump inhibitor was associated with a significantly increased risk of acute interstitial nephritis, relative to past use.

Figure 1

Study flow diagram. *The dashed line indicates that this part of the figure only describes the case identification process. ^†Determined after reviewing patients' hospital discharge information. ^‡Chronic interstitial nephritis with early amyloid disease (n=1); focal segmental glomerulosclerosis (n=1); glomerulonephritis (n=1); light chain cast nephropathy (n=3); minimal change disease with nephrotic syndrome (n=1); multiple myeloma (n=2); systemic lupus erythematosus (n=1); vasculitis (n=1); acute tubular necrosis (n=2); nonsteroidal anti-inflammatory drug nephropathy in context of dehydration (n=1); ‘interstitial nephritis on USS (ultrasound)' (n=1). ^§Determined after consultation with a renal physician.

Figure 2

Determination of current, recent, and past person-years. (a) Patients who only contributed current person-years. (b) Patients who contributed current and recent person-years. (c) Patients who contributed current, recent, and past person-years.