PPIs, H2 blockers may be linked to kidney disease

Proton pump inhibitors and histamine receptor-2 blockers are associated with a slightly increased risk for kidney stones, according to research presented at ASN Kidney Week.

In addition, a related study found that PPI use was associated with a higher risk for chronic kidney disease and kidney failure compared with H2 blockers in the absence of acute kidney injury.

As PPI and H2 blockers may impact urinary excretions of lithogenic factors like calcium and magnesium, Pietro Manuel Ferraro, MD, MS, PhD, of the Catholic University of the Sacred Heart in Rome, Italy, and colleagues aimed to determine if these drugs may increase the risk for developing kidney stones.

They evaluated data on chronic PPI use by 187,330 participants in the Health Professionals Follow-up Study, and the Nurses’ Health Studies I and II. They also performed a subgroup analysis in 6,520 individuals to evaluate cross-sectional associations between PPIs and H2 blockers, and levels of kidney stone components in 24-hour urinary excretions.

There were 12 years of follow-up for PPIs, 26 years for H2 blockers, and a cumulative follow-up of 1,903,725 person-years.

Overall, 3,245 incident symptomatic kidney stone events occurred.

Multivariable analysis, adjusting for age, race, BMI, physical activity, smoking, comorbidities, medication use and nutrient intake, showed PPI use was associated with a 12% higher risk for incident kidney stones (HR = 1.12; 95% CI 1.02-1.24). Results were similar irrespective of duration of use and after restricting the analysis to incident PPI users, but this risk was slightly reduced in a 2-year time-lag analysis.

Similarly, H2 blockers were associated with a 13% increased risk for incident kidney stones (HR = 1.13; 95% CI 1.02-1.24).

In the subgroup analysis, use of PPIs was associated with lower urinary excretion of calcium (P < .001), oxalate (P = .02), citrate (P < .001) and magnesium (P < .001).

“Use of PPIs and H2 blockers is associated with a small increase in risk of incident kidney stones,” Ferraro said in a press release. “Further studies are needed to confirm our findings and to investigate whether the excess risk is related to a particular type of kidney stones such as those made of calcium oxalate.”

In the related study, Yan Xie, MPH, of the VA Saint Louis Health Care System, and colleagues aimed to evaluate current assumptions that PPI-associated chronic kidney disease is secondary to incomplete recovery from acute kidney injury.

“Whether long term adverse renal outcomes are mediated solely by occurrence of [acute kidney injury] is not known,” they wrote.

Using the Department of Veterans Affairs national database, they identified more than 150,000 PPI or H2 blocker users with no history of acute kidney injury, and evaluated for associations between use of these drugs and incidence and progression of chronic kidney disease, and end-stage renal disease in patients with and without acute kidney injury during 5 years follow-up.

Compared with H2 blocker use in the absence of acute kidney injury, PPI use was associated with more than a 30% higher risk for developing chronic kidney disease, a combined endpoint of kidney failure, or greater than a 50% decline in estimated glomerular filtration rate.

“Reliance on [acute kidney injury] as a marker of potential adverse renal events in those treated with PPI is not sufficient,” Xie said in the press release. “Exercising vigilance in PPI use — even in the absence of [acute kidney injury] — and careful attention to kidney function in PPI users may be a reasonable approach.” – by Adam Leitenberger

Reference:

Curhan GC, et al. Abstract #931. Presented at: ASN Kidney Week; Nov. 15-20, 2016; Chicago, IL.

Xie Y, et al. Abstract #3495. Presented at: ASN Kidney Week; Nov. 15-20, 2016; Chicago, IL.

Disclosures: Healio Gastroenterology was unable to confirm relevant financial disclosures at the time of publication.