Antibiotic Use and Risk of Incident Kidney Stones in Female Nurses

Abstract

Rationale & objective: The intestinal microbiome may affect urinary stone disease by modulating the amount of oxalate absorbed from the intestine and subsequently excreted in urine. This study sought to explore the association between antibiotics, which alter the intestinal microbiota, and risk for urinary stone disease.

Study design: Prospective cohort study.

Setting & participants: 5,010 women in the Nurses' Health Study (NHS) I and II who had collected 24-hour urine samples.

Exposures: Use of antibiotics during the age range of 40 to 49 (NHS II), 40 to 59 (NHS I), and 20 to 39 years (both cohorts).

Outcomes: Incident symptomatic urinary stone disease; urine composition.

Analytical approach: Cause-specific hazards regression adjusted for age, body mass index, comorbid conditions, thiazide use, and dietary factors. Follow-up was censored at the time of asymptomatic kidney stones, cancer, or death.

Results: Cumulative use of antibiotics for a total of 2 or more months during the age range of 40 to 49 years (NHS II) and 40 to 59 years (NHS II) was associated with significantly higher risk for developing incident stones compared with no use (pooled HR, 1.48; 95% CI, 1.12-1.96). Similar results were found for the period of 20 to 39 years (pooled HR, 1.36; 95% CI, 1.00-1.84). Results were unchanged after excluding participants who reported urinary tract infection with their stone event or as the most common reason for antibiotic use. Urine composition was generally similar across antibiotic groups except for marginally lower urine pH and citrate values among those taking antibiotics for 2 or more months.

Limitations: Observational design; lack of information for type of antibiotic used; relatively large span of time between antibiotic use and urine collection.

Conclusions: Use of antibiotics for more than 2 months in early adulthood and middle age is associated with higher risk for urinary stone disease in later life.

Keywords: Antibiotics; antibacterial agents; bacterial infection; cohort studies; cumulative antibiotic use; drug effects; intestinal microbiome; kidney stone; lithogenesis; stone formation; urine chemistry; urine composition; urolithiasis; women.