Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

PPIs and the Risk of Chronic Kidney Disease

What is the association?

Protein pump inhibitor (PPI) use was associated with a higher risk of incident chronic kidney disease (CKD) in a study of 10,482 participants who took part in the Atherosclerosis Risk in Communities (ARIC) study. The mean age of participants was 63 years, and 43.9% were male. Researchers found:

• Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication.

• PPI use was associated with incident CKD in unadjusted analysis (HR, 1.45), in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50), and in analysis with PPI ever use modeled as a time-varying variable (HR, 1.35).

• The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (aHR, 1.39) and with propensity score-matched nonusers (HR, 1.76).

• In a replication cohort, PPI use was associated with CKD in all analyses.

• Twice-daily PPI dosing was associated with a higher risk than once-daily dosing (aHR, 1.46 vs 1.15).

Citation: Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. [Published online ahead of print January 11, 2016]. JAMA Intern Med. doi: 10.1001/jamainternmed.2015.7193.

Commentary: PPI are one of the most frequently prescribed medications in the US. For years they were used for all acid-peptic disorders and commonly patients stayed on these medicines long-term once they were started. Over the last 10 years studies have shown a relation between use of PPI and an increase in community acquired pneumonia, C. difficile infections and osteoporosis.1,2,3. Now this study raises the possibility of an association between PPI use and chronic renal insufficiency. It is clear that PPI are very useful and effective agents in the treatment of acid-peptic disorders, and it has become equally clear that they should be used when needed and not continued indefinitely when there is no clear indication. —Neil Skolnik, MD

1. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-2953.

2. Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0128004. doi:10.1371/journal.pone.0128004.

3. Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171(1):33-38.