The Use of Antibiotics and Risk of Kidney Stones

Shivam Joshi; David S. Goldfarb

Disclosures

Curr Opin Nephrol Hypertens. 2019;28(4):311-315. 

In This Article

Antibiotics and Nephrolithiasis

Despite the aforementioned associations with absence of O. formigenes and nephrolithiasis, not all studies have shown such association. For example, in a recent study, three bacterial taxa (Faecalibacterium, Enterobacter, Dorea), but not Oxalobacter were significantly less represented in the fecal samples of calcium stone formers.[26] One possible explanation has been the resistance of O. formigenes to antibiotics. O. formigenes is generally sensitive to a variety of antibiotics commonly used to treat infections, but resistance has been documented with cephalosporins, nitrofurantoin, and broad-spectrum penicillins.[27,28] However, all antibiotics have effects on the abundance of other bacteria in the microbiome, which then may mediate the pathogenesis of nephrolithiasis. Given the complexity of the gut microbiota, it is likely that other taxa and species and not Oxalobacter alone, have a role in determining stool degradation of oxalate and the resulting urinary excretion.[4,29,30]

Many of these issues were recently highlighted in a recent nested case–control study.[31] Using The Health Improvement Network (THIN) database of children and adults in the UK, exposure to antibiotics was shown to prospectively increase the odds of nephrolithiasis. The study included 25 981 patients with nephrolithiasis and 259 797 controls matched for age, sex, and practice. Twelve classes of oral antibiotics were evaluated for an association with stones. Exposure to any of five different antibiotic classes (sulfas, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad-spectrum penicillins) 3–12 months before being diagnosed with nephrolithiasis was associated with kidney stones. The magnitude of the association was the greatest for those exposed at younger ages and 3–6 months before being diagnosed with nephrolithiasis. Importantly, although the strengths of the associations decreased with time since the antibiotic exposure, an association for the development of nephrolithiasis persisted for up to 5 years after receiving antibiotics from all classes except for broad-spectrum antibiotics.

This study was remarkable in its size, longitudinal nature, and ability to evaluate exposure to specific antibiotics. Other strengths of this study included its use of the UK data set, which because of regional factors, allowed for patient matching within practices, adjusting for prior urinary tract infections, and reducing differential ascertainment of antibiotic exposure. However, the study had important limitations, including missing intravenous antibiotic use, lack of stone composition information, microbiome data, and urine chemistries. It potentially did not account for individuals with asymptomatic stones prior to antibiotic prescription. Nonetheless, the study remains one of the more important pieces of evidence in the link between antibiotic use and stone formation.

Similarly, a recent abstract prospectively examined the Nurses' Health Study I and Nurses' Health Study II (NHS II), analyzing 141 518 women over 14 years of follow-up.[32] The result documented 1318 incident kidney stones, of which greater than 77% were composed of calcium. Those women in NHS II who used antibiotics for greater than or equal to 2 months between ages 40 and 59 had an increased relative risk of developing kidney stones (RR 1.62, 95% CI 1.01– 2.60).

There are other possible antibiotic-related factors influencing the development of nephrolithiasis. For example, 70% of bacteria isolated from calcium oxalate stones were resistant to multiple antibiotics, suggesting that surviving bacteria may have a role in stone formation. Although urine in healthy people is generally assumed to be sterile, studies to determine if a urinary microbiome actually exists and has a role in stone formation are ongoing. Another possible variable in some cases could be the direct crystallization of antibiotics, which has occurred with ciprofloxacin and sulfamethoxazole-trimethoprim, and could serve as the basis for heterogeneous nucleation of calcium oxalate or even form stones themselves.[33] Finally, the circumstances of antibiotic usage for infections, which could result in transient periods of increased insensible fluid losses and reduced hydration, may further encourage stone formation.

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