PPIs Could Raise Chronic Kidney Disease Risk
Chronic kidney disease incidence has grown faster than many of its common comorbidities such as diabetes and hypertension, and medications may be an underappreciated driver of this growth.
Chronic kidney disease (CKD) incidence has grown faster than many of its common comorbidities such as diabetes and hypertension, and medications may be an underappreciated driver of this growth.
More than 15 million Americans used prescription proton pump inhibitors (PPIs) in 2013. PPIs are often used inappropriately (estimates of users without an appropriate indication range from 25% to 70%) and frequently taken for indefinite durations.
PPIs have been associated with hip fracture, community-acquired pneumonia, Clostridium difficile infection, acute interstitial nephritis, and acute kidney injury. Previous research has also suggested that PPIs may induce CKD through repeated acute interstitial nephritis episodes or hypomagnesemia states.
A recent study published in JAMA Internal Medicine bolstered the evidence that PPI use is associated with an increased risk of developing CKD.
The data for this prospective community-based cohort study that enrolled more than 10,000 adults were drawn from the Atherosclerosis Risk in Communities study conducted between February 1, 1996, and December 31, 2011.
The study authors excluded participants missing estimated glomerular filtration rate, ratio of urinary albumin to creatinine data, or the use of antihypertensive or anticoagulant medication. Also excluded were patients with prevalent hypertension, diabetes, or cardiovascular disease, as well as those with known end-stage renal disease or an estimated glomerular filtration rate of <15 mL/min/1.73m2.
The researchers found that PPI use was associated with a 20% to 50% increased risk of developing CKD. This association prevailed after adjusting for confounding variables such as demographics, socioeconomic status, clinical measurements, prevalent comorbidities, and concomitant use of medications.
Histamine-2 receptor antagonists, on the other hand, were not associated with an increased risk of acute kidney injury or CKD.
The researchers also found that patients receiving PPIs were more likely to have hypertension, be obese, and receive multiple medications.
One limitation of this research was that documented PPI prescriptions declined in the last few years of the study period, as some PPIs became OTC. Thus, the researchers may not have captured the full scope of PPI use.
Further research should explore whether PPI use itself is a direct cause of CKD and, if so, what mechanisms may be at play.