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.