INTRODUCTION
Proton pump inhibitors (PPIs) are primarily indicated for both the treatment and prevention of acid-related disorders, such as gastroesophageal reflux disease[GERD], peptic ulcers and non-steroidal anti-inflammatory drugs [NSAIDs] bleeding prophylaxis.1 Given the combination of high efficacy with low toxicity and safety of short-term use, PPIs widely prescribed and are among the top 10 most frequently used classes of drugs worldwide.2,3 However, the overutilization of PPIs became health concern, and 40% to 60% were taking a PPI with no appropriate indication.4 Overutilization of PPIs not only increased heathcare cost expenditure but have also been linked to various adverse effects.4 Observational studies have shown that long-term use of PPIs was associated with Clostridium difficile infection, community-acquired pneumonia, hypomagnesemia, bone fractures, rheumatoid arthritis and type 2 diabetes5-9. Concerns have been raised about increased risk of kidney disease in PPIs users.
Chronic Kidney Disease (CKD) is a condition where kidneys fail to function optimally. It is characterized by progressive loss of kidney function that can eventually result in end-stage renal disease (ESRD).10 CKD is an important contributor to morbidity and mortality worldwide with a global prevalence of CKD 9.1% in 2017, resulting in 35.8 million disability-adjusted life years and 1.2 million deaths.11Risk factors influencing CKD are complex, including the unhealthy lifestyles, obesity, cardiovascular disease, diabetes mellitus (DM), hypertension and inappropriate drugs use.11-13 The growing drugs use, like NSAIDs, may also be a contributor to the higher prevalence of CKD.13,14 There is a growing evidence that PPI use might affect kidney function and thus result in CKD.15-18 A meta-analysis of three observational studies found that PPI use was associated with increased risk of CKD (risk ratios [RR] 1.29, 95% Confidence Interval [CI], 1.22–1.36).16 These observational studies are thought-provoking but have important limitations to the evidence base, such as either inadequate assessment of exposures through retrospective recall or administrative claims data, or insufficient adjustment of important confounders such as lifestyle habits.1,16A recent randomized controlled trial including over 17 000 participants found that Pantoprazole seemed to have a modest, although not statistically significant, greater risk of CKD compared with placebo (OR 1.17; 95% CI 0.94 to 1.15).19 However, this trial was questioned with a short follow-up time and insufficient statistical power.20,21
Given the high prevalence of both PPIs use and CKD incident, understanding their association may have important influence on the clinical practice. We therefore performed this prospective cohort study to examine the association between PPI use and incident CKD in the general population using the UK biobank dataset.