Clinical Edge

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PPIs and Risk of Incident CKD or ESRD

J Am Soc Nephrol; ePub 2016 Apr 14; Xie, Bowe, et al

Publish date:

Proton pump inhibitor (PPI) use is associated with increased risk of chronic kidney disease (CKD), CKD progression, and end state renal disease (ESRD), according to a cohort study of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (n=20,270) and followed over 5 years to ascertain renal outcomes. Researchers found:

• The PPI group had an increased risk of incident eGFR <60 ml/min per 1.73 m2 and of incident CKD (HR=1.22) vs with the H2 blockers group.

• Patients treated with PPI also had a significant elevated risk of doubling of serum creatinine level (HR=1.53), of eGFR decline >30% (HR=1.32), and of ESRD (HR=1.96).

• There was also a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31 to 90 days, 91 to 180 days, 181 to 360 days, and 361 to 720 days compared with those exposed for ≤30 days.

Citation: Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. [Published online ahead of print April 14, 2016]. J Am Soc Nephrol. doi:10.1681/ASN.2015121377.

Commentary: We need to be careful when analyzing information from observational studies. In this cohort study, 2 groups, 1 prescribed PPI and 1 prescribed H2-receptor blockers, were followed and compared over 5 years. Patients who were on PPIs developed CKD at a higher rate than those on H2 blockers. The problem, however, with observational studies is the possibility that a relationship that is observed between 2 variables may not be causally related. For instance, it may be that individuals who have a greater burden of medical illness, which might in itself lead to a higher incidence of CKD, may also have a higher incidence of more severe upper GI symptoms, leading to prescriptions for PPIs over H2-blockers. This study is interesting, but far from definitive. Other studies have shown long-term effects of PPI include an increase in osteoporosis, pneumonia, and Clostridium difficile infection.1,2,3 The present study supports the conclusion that patients who need PPIs should be prescribed them and patients should not stay on PPIs indefinitely if they don’t need them. —Neil Skolnik, MD

1. Fraser LA, Leslie WD, Targownik LE, et al. The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study. Osteoporosis Int. 2013;24(4):1161-1168. doi:10.1007/s00198-012-2112-9.

2. Gulmez SE, Holm A, Frederiksen H, Jensen TG, Pedersen C, Hallas J. Use of proton pump inhibitors and the risk of community-acquired pneumonia. Arch Intern Med. 2007;167(9):950-955. doi:10.1001/archinte.167.9.950.

3. Dial S, Delaney JAC, Barkun AN, Suissa S. Use of gastric acid–suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA. 2005;294(23):2989-2995.

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