Proton Pump Inhibitors and Increased Risk of Interstitial Nephritis: A Nationwide Nested Case-Control Study using Routinely Collected Data from New Zealand
METHODS: We conducted a nested case-control study using routinely collected national health and drug dispensing data from New Zealand. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of PPI use between 2005 and 2009. Cases had a first diagnosis after cohort entry of interstitial nephritis confirmed by hospital discharge letter or death record and renal histology (definite, n=46), or discharge letter or death record only (probable, n=26). Ten controls, matched by birth year and sex, were randomly selected for each case. PPI exposure was ascertained through pharmacist dispensing records. Odds ratios and 95% confidence intervals were estimated with conditional logistic regression. Incidence rates with 95% confidence intervals were estimated using the Poisson distribution.
RESULTS: In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (OR) comparing current use of PPIs to past use was 5.16 (95% CI 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 per 100,000 person-years were 11.98 (95% CI 9.11 – 15.47) and 1.68 (95% CI 0.91 – 2.86) for current and past use respectively.
CONCLUSIONS: Current use of a PPI was associated with significantly increased risk of interstitial nephritis, relative to past use. The absolute risks were very low, but substantially higher in older users.