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Certain oral antibiotics tied to increased risk of kidney stones

Pearl Toh
23 Jul 2018

Exposure to certain oral antibiotics was associated with a greater risk of developing kidney stones, particularly for exposure that occurred recently and at a younger age, reveals a study.

“These findings suggest that exposure to some oral antibiotics is a novel risk factor for nephrolithiasis, one that may be modifiable for the 30 percent of patients who receive inappropriate outpatient prescriptions for antibiotics,” said lead author Dr Gregory Tasian of Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, US.

The population-based, nested case-control study was based on electronic health record data of 25,981 children and adult cases with nephrolithiasis who were matched to 259,797 controls by sex, age, and index date in the THIN* database. [J Am Soc Nephrol 2018;doi:10.1681/ASN.2017111213]   

Five classes of oral antibiotics were associated with a higher rate of nephrolithiasis diagnosis within 3–12 months of exposure. Patients exposed to sulfa antibiotics had the highest odds of developing nephrolithiasis (adjusted odds ratio [OR], 2.33, 95 percent confidence interval [CI], 2.19–2.48), followed by exposure to cephalosporins (HR, 1.88, 95 percent CI, 1.75–2.01), fluoroquinolones (HR, 1.67, 95 percent CI, 1.54–1.81), nitrofurantoin/methenamine (HR, 1.70, 95 percent CI, 1.55–1.88), and broad-spectrum penicillins (HR, 1.27, 95 percent CI, 1.18–1.36).  

The risk for nephrolithiasis was strongest for recent antibiotic exposure during 3–6 months before diagnosis (p<0.001).

“The strength of the associations decreased with greater time from the antibiotic prescription, but the odds of nephrolithiasis diagnosis remained elevated for up to 5 years from antibiotic exposure … for all classes except broad-spectrum penicillins,” said the researchers.

Also, the younger the age of antibiotic exposure, the greater the risk of nephrolithiasis (p<0.001). The shape of the association curve varied by antibiotic class, which according to the researchers, “suggests that risk at a given age may depend not only on the age at exposure, but also the particular [type of] antibiotic given.”

“If confirmed by others, these results may help inform antibiotic selection when alternative options exist,” suggested Tasian and co-authors.

Nonetheless, the researchers acknowledged that antibiotic exposure was based on prescription data, which did not necessarily entail adherence to the drug. Nonadherence to treatment would nullify the associations.  

It was believed that antibiotics may change the composition of the intestinal microbiome and select for multidrug resistant bacteria that promote stone formation in the kidney. [Cell 2014;158:705-721; PLoS One 2015;10:e0139575] A previous study has shown that multidrug resistant nonurease-producing bacteria were found in calcium-based kidney stones from patients without urinary tract infection. [Nephrol Dial Transplant 2012;27:41254130] The researchers also did not discount the possibility of direct antibiotic crystallization in the kidney, as what has been reported for ciprofloxacin and sulfamethoxazole-trimethoprim. [J Urol 2000;164:438]

“Given that children receive more antibiotics than any other age group, and 30 percent of antibiotics prescribed during ambulatory care visits are inappropriate, these findings provide another reason to reduce inappropriate outpatient antibiotic use,” they added.

“These results have implications for the pathogenesis of the disease and for the rising incidence of nephrolithiasis, particularly among children.”

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Most Read Articles
Stephen Padilla, 02 Oct 2019
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