There is a reported association of developing CKD with exposure to proton pump inhibitors in several small cohorts in the literature. This is particularly concerning given the widespread use of these drugs and the rising prevalence of CKD (defined as an eGFR < 60 mL/min) that currently affects 1 in 7 adults in the United States - the reasons for which are not clear at present. Proton pump inhibitors are commonly prescribed drugs but are frequently given to individuals who also have significant comorbidities such as diabetes and obesity (also known risk factors for the development of CKD). A large observational cohort study that is either able to detect a change in the GFR over time (calculated from serum creatinine, age, gender and race) or the development of new onset CKD, defined as an estimated GFR < 60mL/min, following the initiation of PPI use (after adjustment for major comorbidities) would result in significant change in clinical practice worldwide.
Currently small cohort studies have been plagued with inadequate adjustment, inability to create propensity matched control cohorts. As a result, there has yet to be a significant change in clinical practice. The results of a large adequately powered, propensity score matched study or a study that excludes individuals with comorbidities commonly associated with CKD would have an immediate impact on patient care.
Target Cohort – patients aged age 18 years and older with chronic exposure to proton pump inhibitors who do not have evidence of chronic kidney disease (defined as an estimated GFR of < 60mL/min) at the time of initiation of therapy
Comparator group: Patients aged 18 years and older with no exposure to proton pump inhibitors
Outcome: Incidence of chronic kidney disease
Model: Cox model for time to event analysis (development of CKD) with stratification by drug exposure duration. Regression for assessing rate of decline in GFR associated with exposure to PPI
Adjustment: propensity score using age, diabetes, hypertension, African American race and eGFR at the time of entry into the study.
Potential exclusions: patients exposed to known nephrotoxic agents - specifically chronic NSAID use.