Oral Antibiotic Exposure and Kidney Stone Disease

Abstract

Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case-control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Exposure to any of five different antibiotic classes 3-12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (<0.001) and 3-6 months before index date (<0.001), with all but broad-spectrum penicillins remaining statistically significant 3-5 years from exposure. Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.

Antibiotics and Kidney Stones: Perturbation of the Gut-Kidney Axis

“…The results of this study are consistent with 2 recent case-control studies from Tasian et al 14 and Zampini et al, 15 which found that oral antibiotic use was associated with increased odds of kidney stones among children and adults. Zampini et al 15 found that adults with an active episode of nephrolithiasis were significantly more likely to have taken oral antibiotics in the last year, but not the last 30 days, compared with individuals with no history of the disease.…”

“…In the Zampini study, both oral antibiotic use and incidence of nephrolithiasis were more associated with the urinary tract microbiome than the gut microbiome. Using incidence density sampling, Tasian et al 14 examined 25,981 patients with nephrolithiasis that were matched to 259,797 controls on age, sex, and practice at the date of diagnosis. The adjusted odds ratios for nephrolithiasis were 2.33 for sulfas, 1.88 for cephalosporins, 1.67 for fluoroquinolones, 1.70 for nitrofurantoin, and 1.27 for broad-spectrum penicillins.…”

Profiling the urinary microbiome in men with calcium-based kidney stones

“…Similar increases in prevalence exist in a variety of systemic diseases, such as diabetes, cardiovascular disease and metabolic syndrome [4][5][6]. Moreover, a recent population-based study demonstrated that multiple classes of oral antibiotics exposure is associated with increased odds of nephrolithiasis [7]. Interestingly, human microbiome could be affected by all these factors, indicating its potential role in the pathophysiology of nephrolithiasis.…”

Microbial contributions to oxalate metabolism in health and disease

“…The mammalian intestinal microbiota can partially protect against oxalate toxicity by oxalate degradation [15][16][17][18]. Two recent large-scale epidemiological studies associated antibiotic use with increased nephrolithiasis risk [19,20], presumably via a perturbed microbiota [21]. Multiple gut microbes can degrade oxalate [22], including Oxalobacter formigenes, an oxalate autotroph [23][24][25][26][27].…”