CHOP study links antibiotic use with risk of kidney stones

Overuse of antibiotics can promote the growth of drug-resistant "superbugs." It also can disrupt the community of useful bacteria that populate our insides, in ways that may be tied to a variety of health conditions, such as obesity.

A new Children's Hospital of Philadelphia study finds yet another reason to be wary of the drugs: Some appear to raise a person's risk of developing kidney stones — those hard deposits that can become stuck in the urinary tract, with painful consequences.

In a review of nearly 300,000 patient records from the United Kingdom, the researchers found elevated rates of kidney stones in those who took five categories of oral antibiotics, among them broad-spectrum penicillins and the class that includes Cipro.

The study, published Thursday in the Journal of the American Society of Nephrology, does not prove those antibiotics cause kidney stones, but evidence from previous studies suggests that it is at least plausible to draw that conclusion. The new findings were clear enough that one of the study leaders, pediatric urologist Gregory E. Tasian, said that when appropriate, he would consider looking for alternatives to the antibiotics that were associated with a higher risk of kidney stones.

"These findings just add weight to the large body of evidence that antibiotics should be prescribed for appropriate reasons and used judiciously," he said.

Antibiotics are life-saving drugs. But in as many as one-third of cases, they are prescribed to patients who do not really need them — for example, those who are likely to get better on their own, or those who are infected with viruses, which do not respond to the drugs.

The team of authors, which also included researchers from Merck & Co., the University of Pennsylvania, and New York University Langone Medical Center, reviewed the records of patients who developed kidney stones at least three months after taking antibiotics. That's because the stones take weeks or months to develop, and the authors wanted to exclude any patients who might develop kidney stones for unrelated reasons.

The strongest connection between antibiotics and kidney stones was found in the category called sulfa drugs, which includes Bactrim. Patients who had taken sulfa drugs were more than twice as likely to develop kidney stones three to 12 months afterward than people who had not taken the medicines, the researchers found.

A lesser, but still significant, connection with kidney stones was found for four other kinds of antibiotics: cephalosporins, fluoroquinolones (the class that includes Cipro), nitrofurantoin (sold as Macrobid), and broad-spectrum penicillins.

For example, patients who had taken broad-spectrum penicillins — penicillins coupled with an additional active ingredient — were about 30 percent more likely to develop kidney stones during that period than people who had not taken the drugs. Regular penicillin did not appear to have an impact on kidney stones.

Kidney stones affect 9 percent of the U.S. population, occurring more often in older people. While the rate has gone up in recent years, there is an easy way to reduce it: drink adequate amounts of water. Kidney stones are formed by chemicals in the urine, and the concentration of these chemicals is generally higher in people who fail to drink enough.

Joshua M. Stern, a New York urologist who was not part of the study, said the connection between antibiotics and kidney stones is likely complex, brought about by a broad disruption in the microbiome that fosters an ideal environment for stone formation, he said. While more research is needed to explore how that works, the new study is an important warning sign, he said.

"This study really shows at a large scale that antibiotics are associated with increased kidney stone risk," said Stern, also director of endourology at the Montefiore Health System.

The findings held true regardless of whether the patients were taking additional drugs or suffered from other ailments that might predispose them to developing kidney stones, said Tasian, who led the study with Michelle Denburg, a pediatric nephrologist at CHOP.

And the results may relate to other conditions as well, Tasian said. Kidney stones are associated with a risk of high blood pressure, decreased bone density, and heart disease, so it would be worth further research to see if those disorders, too, are associated with antibiotic use, he said.

One encouraging sign: While the risk of kidney stones remained higher than normal beyond the three- to 12-month period for those who took these antibiotics, it declined somewhat — suggesting that the patients' internal bacteria had started to recover, Stern said.

"That suggests your core microbiome really does want to protect itself," he said.