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

Tasian, Gregory E.; Miller, Aaron W.; Lange, Dirk

doi:10.1053/j.ajkd.2019.07.021

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…This is the first amplicon gene sequencing identification of fungi in these three mineralogies and is consistent with previous culturing studies that documented Candida growth from powdered CaOx stone fragments (9). It has also recently been observed that idiopathic stone forming patients have developed an imbalance in the normal healthy composition of the bacterial communities inhabiting the gut (dysbiosis) (17,19,22). These dysbiosis studies have focused on gut microbiome networks that include the oxalate-degrading anaerobic bacterium Oxalabacter formigenes, whose activity is strongly controlled by changes in patient diet (19,23).…”

Section: Phylogenetic Diversity Of the Entombed In Vivo Microbiomesupporting

confidence: 88%

In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis

et al. 2021

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Background: Human kidney stones form via repeated events of mineral precipitation, partial dissolution and reprecipitation, which are directly analogous to similar processes in other natural and man-made environments where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fidelity metagenomic (microscopy-to-omics) analyses, applicable to all forms of biomineralization, have been applied to assemble definitive evidence of in vivo microbiome entombment during urolithiasis. Methods: Stone fragments were collected from a randomly chosen cohort of 20 patients using standard percutaneous nephrolithotomy (PCNL). Fourier transform infrared (FTIR) spectroscopy indicated that 18 of these patients were calcium oxalate (CaOx) stone formers, while one patient each formed brushite and struvite stones. This apportionment is consistent with global stone mineralogy distributions. Stone fragments from 7 of these 20 patients (5 CaOx, 1 brushite and 1 struvite) were thin sectioned and analyzed using brightfield (BF), polarization (POL), confocal, superresolution autofluorescence (SRAF) and Raman techniques. DNA from remaining fragments, grouped according to each of the 20 patients, were analyzed with amplicon sequencing of 16S rRNA gene sequences (V1-V3, V3-V5) and internal transcribed spacer (ITS1, ITS2) regions. Results: Bulk entombed DNA was sequenced from stone fragments in 11 of the 18 CaOx patients, as well as the brushite and struvite patients. These analyses confirmed the presence of an entombed low-diversity community of bacteria and fungi, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Aspergillus niger. Bacterial cells ~1 µm in diameter were also optically observed to be entombed and well-preserved in amorphous hydroxyapatite spherules and fans of needle-like crystals of brushite and struvite. Conclusions: These results indicate a microbiome is entombed during in vivo CaOx stone formation. Similar processes are implied for brushite and struvite stones. This evidence lays the groundwork for future in vitro and in vivo experimentation to determine how the microbiome may actively and/or passively influence kidney stone biomineralization.

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Section: Phylogenetic Diversity Of the Entombed In Vivo Microbiomesupporting

confidence: 88%

In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis

et al. 2021

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“…In the case of incomplete resilience, it is logical to expect a reduction or even disappearance of certain functions performed by the missing bacteria, possibly the oxalotrophic bacteria, which could promote the development of calcium oxalate stones [ 59 , 60 , 61 ]. Studies in humans showed that oral antibiotic use was associated with an increased risk of kidney stones [ 62 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Gut and Urinary Microbiota in Cats with Kidney Stones

Joubran,

Roux,

Serino

et al. 2024

Microorganisms

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Upper urinary tract urolithiasis is an emerging disease in cats, with 98% of kidney stones composed of calcium oxalate. In humans, disturbances in the intestinal and urinary microbiota are suspected to contribute to the formation of calcium oxalate stones. We hypothesized that similar mechanisms may be at play in cats. This study examines the intestinal and urinary microbiota of nine cats with kidney stones compared to nine healthy cats before, during, and after treatment with the antibiotic cefovecin, a cephalosporin. Initially, cats with kidney stones displayed a less diverse intestinal microbiota. Antibiotic treatment reduced microbiota diversity in both groups. The absence of specific intestinal bacteria could lead to a loss of the functions these bacteria perform, such as oxalate degradation, which may contribute to the formation of calcium oxalate stones. This study confirms the presence of a distinct urobiome in cats with kidney stones, characterized by greater richness and diversity compared to healthy cats. These findings highlight the potential of microbiota modulation as a strategy to prevent renal lithiasis in cats.

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“…6 Therefore, it is biologically plausible that antibiotics could increase the risk of kidney stones through the gastrointestinal and urinary microbiome. 12,13 Prior studies have reported an increased risk of kidney stones after antibiotic use. A large, electronic health record-based study demonstrated that the prior use of specific oral antibiotic classes, namely sulfas, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad-spectrum penicillins, was associated with an increased risk of kidney stones, with a greater risk observed in a more recent period after antibiotic use.…”

Section: Introductionmentioning

confidence: 99%

“…6 Therefore, it is biologically plausible that antibiotics could increase the risk of kidney stones through the gastrointestinal and urinary microbiome. 12,13…”

Section: Introductionmentioning

confidence: 99%

Outpatient Antibiotic Use is Not Associated with an Increased Risk of First-Time Symptomatic Kidney Stones

Vaughan

Barreto

Mehta

et al. 2023

JASN

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Significance Statement Antibiotics modify human microbiomes and may contribute to kidney stone risk. In a population-based case-control study using 1247 chart-validated first-time symptomatic kidney stone formers and 4024 age- and sex-matched controls, the risk of kidney stones was transiently higher during the first year after antibiotic use. However, this risk was no longer evident after adjustment for comorbidities and excluding participants with prior urinary symptoms. Findings were consistent across antibiotic classes and the number of antibiotic courses received. This suggests that antibiotics are not important risk factors of kidney stones. Rather, kidney stones when they initially cause urinary symptoms are under-recognized, resulting in antibiotic use before a formal diagnosis of kidney stones (i.e., reverse causality). Background Antibiotics modify gastrointestinal and urinary microbiomes, which may contribute to kidney stone formation. This study examined whether an increased risk of a first-time symptomatic kidney stone episode follows antibiotic use. Methods A population-based case-control study surveyed 1247 chart-validated first-time symptomatic kidney stone formers with a documented obstructing or passed stone (cases) in Olmsted County, Minnesota, from 2008 to 2013 and 4024 age- and sex-matched controls. All prescriptions for outpatient oral antibiotic use within 5 years before the onset of symptomatic stone for the cases and their matched controls were identified. Conditional logistic regression estimated the odds ratio (OR) of a first-time symptomatic kidney stone across time after antibiotic use. Analyses were also performed after excluding cases and controls with prior urinary tract infection or hematuria because urinary symptoms resulting in antibiotic prescription could have been warranted because of undiagnosed kidney stones. Results The risk of a symptomatic kidney stone was only increased during the 1-year period after antibiotic use (unadjusted OR, 1.31; P = 0.001), and this risk was attenuated after adjustment for comorbidities (OR, 1.16; P = 0.08). After excluding cases and controls with prior urinary symptoms, there was no increased risk of a symptomatic kidney stone during the 1-year period after antibiotic use (unadjusted OR, 1.04; P = 0.70). Findings were consistent across antibiotic classes and the number of antibiotic courses received. Conclusions The increased risk of a first-time symptomatic kidney stone with antibiotic use seems largely due to both comorbidities and prescription of antibiotics for urinary symptoms. Under-recognition of kidney stones that initially cause urinary symptoms resulting in antibiotic use may explain much of the perceived stone risk with antibiotics (i.e., reverse causality).

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

Cited by 7 publications

References 25 publications

In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis

In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis

Gut and Urinary Microbiota in Cats with Kidney Stones

Outpatient Antibiotic Use is Not Associated with an Increased Risk of First-Time Symptomatic Kidney Stones

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