In the Journals

PPIs linked to increased risk for chronic kidney disease

Proton pump inhibitor use was associated with increased risk for incident chronic kidney disease, progression of chronic kidney disease and end-stage renal disease, according to data from a recent study.

“The results emphasize the importance of limiting PPI use only when it is medically necessary, and also limiting the duration of use to the shortest duration possible,” Ziyad Al-Aly, MD, FASN, of the Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in Saint Louis, said in a press release. “A lot of patients start taking PPIs for a medical condition, and they continue much longer than necessary.”

Al-Aly and colleagues used national VA databases to identify 20,270 new users of H2-receptor antagonists and 173,321 new users of PPIs without kidney disease at baseline, and followed them for more than 5 years to evaluate associations between PPI use and risk for incident chronic kidney disease, progression of chronic kidney disease and end-stage renal disease.

Adjusted Cox survival models showed the PPI group had an increased risk for incidence of estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2 (HR = 1.22; 95% CI, 1.18-1.26) and an increased risk for incident chronic kidney disease (HR = 1.28; 95% CI, 1.23-1.34) compared with the H2-receptor antagonist group. The PPI group also had an increased risk for doubled serum creatinine levels (HR = 1.53; 95% CI, 1.42-1.65), of eGFR reductions greater than 30% (HR = 1.32; 95% CI, 1.28-1.37), and of end-stage renal disease (HR = 1.96; 95% CI, 1.21-3.18).

Compared with patients who received PPIs for 30 days or less, there was a graded association between length of PPI use and risk for renal outcomes among patients who took PPIs for 31-90, 91-180, 181-360 and 361-720 days. Sensitivity analyses of one-to-one propensity score-matched cohorts of patients receiving H2-receptor antagonists vs. PPIs and patients taking PPIs vs. controls showed similar results.

These results expand on those from a recent observational cohort study performed by Lazarus and colleagues, which found PPI users had a significantly higher risk for incident chronic kidney disease compared with nonusers.

“Taken together, these studies shed light on an important adverse event with long-term PPI use,” Dennis G. Moledina, MD, and Mark A. Perazella, MD, both from the section of nephrology, department of internal medicine at Yale School of Medicine, wrote in a related editorial. “The results of these studies associating PPI use with [chronic kidney disease] in the community lead one to conclude that, although observational studies cannot prove causation, there is an extremely strong association. These epidemiologic observational data provide preliminary support for an increased risk of [chronic kidney disease] in patients using PPIs ... In the end, the message for physicians and patients is that PPI use should be discouraged when a clear cut indication does not exist, despite the apparent short-term safety.”

The study results also provide insights for future drug safety research, according to the press release. “The study serves as a model to leverage the availability of Big Data — with VA data being a prime example — and advanced analytics to determine long term safety profiles of commonly used medications and promote pharmacovigilance,” Yan Xie, MPH, also from the Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in Saint Louis, said in the press release. – by Adam Leitenberger

Disclosure: The researchers and editorial authors report no relevant financial disclosures.

Proton pump inhibitor use was associated with increased risk for incident chronic kidney disease, progression of chronic kidney disease and end-stage renal disease, according to data from a recent study.

“The results emphasize the importance of limiting PPI use only when it is medically necessary, and also limiting the duration of use to the shortest duration possible,” Ziyad Al-Aly, MD, FASN, of the Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in Saint Louis, said in a press release. “A lot of patients start taking PPIs for a medical condition, and they continue much longer than necessary.”

Al-Aly and colleagues used national VA databases to identify 20,270 new users of H2-receptor antagonists and 173,321 new users of PPIs without kidney disease at baseline, and followed them for more than 5 years to evaluate associations between PPI use and risk for incident chronic kidney disease, progression of chronic kidney disease and end-stage renal disease.

Adjusted Cox survival models showed the PPI group had an increased risk for incidence of estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2 (HR = 1.22; 95% CI, 1.18-1.26) and an increased risk for incident chronic kidney disease (HR = 1.28; 95% CI, 1.23-1.34) compared with the H2-receptor antagonist group. The PPI group also had an increased risk for doubled serum creatinine levels (HR = 1.53; 95% CI, 1.42-1.65), of eGFR reductions greater than 30% (HR = 1.32; 95% CI, 1.28-1.37), and of end-stage renal disease (HR = 1.96; 95% CI, 1.21-3.18).

Compared with patients who received PPIs for 30 days or less, there was a graded association between length of PPI use and risk for renal outcomes among patients who took PPIs for 31-90, 91-180, 181-360 and 361-720 days. Sensitivity analyses of one-to-one propensity score-matched cohorts of patients receiving H2-receptor antagonists vs. PPIs and patients taking PPIs vs. controls showed similar results.

These results expand on those from a recent observational cohort study performed by Lazarus and colleagues, which found PPI users had a significantly higher risk for incident chronic kidney disease compared with nonusers.

“Taken together, these studies shed light on an important adverse event with long-term PPI use,” Dennis G. Moledina, MD, and Mark A. Perazella, MD, both from the section of nephrology, department of internal medicine at Yale School of Medicine, wrote in a related editorial. “The results of these studies associating PPI use with [chronic kidney disease] in the community lead one to conclude that, although observational studies cannot prove causation, there is an extremely strong association. These epidemiologic observational data provide preliminary support for an increased risk of [chronic kidney disease] in patients using PPIs ... In the end, the message for physicians and patients is that PPI use should be discouraged when a clear cut indication does not exist, despite the apparent short-term safety.”

The study results also provide insights for future drug safety research, according to the press release. “The study serves as a model to leverage the availability of Big Data — with VA data being a prime example — and advanced analytics to determine long term safety profiles of commonly used medications and promote pharmacovigilance,” Yan Xie, MPH, also from the Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in Saint Louis, said in the press release. – by Adam Leitenberger

Disclosure: The researchers and editorial authors report no relevant financial disclosures.