Proton pump inhibitors and kidney disease: a self-controlled case series and cohort study

Date of Approval: 
2016-08-15 00:00:00
Lay Summary: 
Proton-pump inhibitor (PPI) drugs, such as lansoprazole and omeprazole, are commonly prescribed for the treatment and prevention of stomach ulcers, and gastric reflux (indigestion or heartburn). Research suggests that PPIs are linked with a kidney condition called acute interstitial nephritis (AIN) that can impair kidney function. Taking a PPI might therefore be associated with a measurable decline in kidney function. This decline can either be sudden, which is termed acute kidney injury (AKI), or gradual, which is termed chronic kidney disease (CKD). Indeed recent research points to a link between PPIs and CKD. However, it is likely that patients prescribed PPIs have other characteristics that might make them more likely to have kidney problems and the existing studies have a number of limitations; our study therefore aims to investigate the association between PPIs and kidney disease, and to investigate whether different PPIs have different effects on kidney disease.
Technical Summary: 
We aim to assess the link between PPIs and renal disease. We will use: i) a self-controlled case series study (SCCS) to compare AKI, within individuals, during periods of exposure to PPIs compared to baseline unexposed time; and ii) a cohort study to investigate the effect of omeprazole on kidney disease compared to other PPIs. In the SCCS, we will identify new PPI users who have at least one AKI event. We will use conditional Poisson regression to investigate the relative rate of AKI during periods exposed to PPIs compared to that during unexposed periods. We will repeat the analysis using cataract surgery as a negative control outcome. We do not expect cataract surgery to be associated with PPIs, a negative association in this analysis will therefore increase our confidence in any positive association observed between PPIs and AKI. In the cohort study, we will identify new users of omeprazole, lansoprazole, and pantoprazole. Existing research has focussed on the renal effects of PPIs as a class, there is little information regarding whether different PPIs have different effects on renal outcomes. We will therefore use Poisson regression to compare rates of AKI and incident CKD during omeprazole use (first generic introduced and most commonly prescribed PPI) compared to other PPIs.
Health Outcomes to be Measured: 
Hospitalisation for acute kidney injury
Application Number: 
16_149
Collaborators: 

Ian Douglas - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Adrian Root - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kaiti Tseng - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kathryn Mansfield - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Laurie Tomlinson - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )

Linkages: 
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation