Duration and dosing of Proton Pump Inhibitors associated with high incidence of chronic kidney disease in population-based cohort

Abstract

BackgroundProton Pump Inhibitors (PPIs) have been associated with chronic kidney disease (CKD). Our objective was to quantify the association between PPI use and incident CKD in a population-based cohort.Methods and findingsWe used a population-based retrospective cohort, including people aged 15 years or over, between January 1, 2005 and December 31, 2012. PPI use was measured in a follow-up session by recording prescriptions. Incident CKD was defined as an estimated glomerular filtration rate < 60 ml/ min/1.73 m2 and/or urinary albumin level to creatinine level ≥ 30 mg/g, in two or more determinations over a period of at least 3 months of the follow-up. Proton Pump Inhibitor use was associated with incident CKD in analysis adjusted for different clinical variables (Hazard Ratio (HR) 1.18; 95% CI 1.04–1.51) in individuals who used PPI in the basal visit (HR 1.37; 95% CI 1.25–1.50) and in those who started to use PPI during the follow-up. High doses of PPI increased the risk of incident CKD (HR 1.92; 95%CI 1.00–6.19) for any type of exposure to PPIs (HR 2.40; 95%CI 1.65–3.46) and for individuals who used high doses throughout the follow-up. This risk of incident CKD increased after three months’ exposure to PPIs, (HR1.78; 95% CI 1.39–2.25) between the third and sixth months and (HR 1.30; 95%CI 1.07–1.72) after the sixth month.ConclusionsPPI use is associated with a higher risk of incident CKD. This association is greater for high doses and becomes apparent after three months’ exposure.

Comment on “Polypharmacy and Kidney Function in Community-Dwelling Adults Age 60 Years and Older: A Prospective Observational Study”

“…In summary, although other studies have found an association between PPI use and a decline in kidney function, 2,3 we cannot confirm such an association in our study. In our study, NSAID use, independent of PPI use, contributed to a worsening of kidney function over 24 months among the relatively healthy older adults aged 60 years and older enrolled in our study.…”

“…According to the Beers criteria, long-term use of NSAIDs due to gastrointestinal complications, including gastroduodenal ulcer, gastrointestinal bleeding, and perforation, should be avoided; however, it is emphasized that NSAIDs should be used in combination with proton-pump inhibitors (PPIs) if pain cannot be controlled by other alternative analgesics. 3 This means that in Ernst et al's study, the patients who used NSAIDs for more than 24 months had been probably or should have been receiving PPI at the same time. 1 PPIs are one of the most commonly prescribed drugs in older people, and it is estimated that between 25% and 70% of the prescriptions have no appropriate indication.…”

Safety and Complications of Long-Term Proton Pump Inhibitor Therapy: Getting Closer to the Truth

“…For example, a recent observational study of 5254 proton pump inhibitor users versus a smaller number of never users found an increased risk of kidney disease after only 3 month's medication exposure. 16 This finding means that the current study's multiyear duration, in a larger population, would have been expected to detect comparable causal exposure-disease associations.…”

Investigating the association of proton pump inhibitors with chronic kidney disease and its impact on clinical practice and future research: a review

“…At the 5 year follow up, participants using PPIs were found to have a greater incidence of developing long-term renal outcomes as opposed to H2 receptor blockers [ 10 ]. Higher doses of PPIs together with their longer duration of use were reported to be associated with a greater risk of CKD [ 15 ]. A population-based retrospective cohort study conducted in Spain that involved 46,541 participants suggested that high doses of PPIs augmented the risk of incident CKD (HR 1.92; 95% CI 1.00–6.19).…”