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Oral antibiotics up risk of kidney stones

Tristan Manalac
19 May 2018

Taking oral antibiotics appears to increase the risk of nephrolithiasis, according to a recent study. Moreover, the risk seems to be compounded for  with recent antibiotic exposure and those who were exposed at a younger age.

Exposure to sulfas (odds ratio [OR], 2.33; 95 percent CI, 2.19–2.48; p<0.001), cephalosporins (OR, 1.88; 1.75–2.01; p<0.001) and fluoroquinolones (OR, 1.67; 1.54–1.81; p<0.001) increased the risk of being diagnosed with nephrolithiasis 3–12 months after prescription. [J Am Soc Nephrol 2018;doi:10.1681/ASN.2017111213]

The same was true for nitrofurantoins (OR, 1.7; 1.55–1.88; p<0.001) and broad-spectrum penicillins (OR, 1.27; 1.18–1.36; p<0.001). Receiving treatment for Helicobacter pylori 3–12 months prior also increased the risk of nephrolithiasis diagnosis (OR, 1.79; 1.21–2.65; p=0.003).

Age significantly affected the relationship between oral antibiotic use and nephrolithiasis development (p<0.001).  Those who were exposed at younger ages had much higher odds of developing nephrolithiasis than those who took the antibiotics at an older age.

Recent exposure was likewise a significant interaction factor for all oral antibiotic classes examined. Those who were exposed to sulfas (OR, 2.63; 2.42–2.85; p<0.001), cephalosporins (OR, 2.26; 2.06–2.48; p<0.001), fluoroquinolones (OR, 1.98; 1.77–2.22; p<0.001), nitrofurantoins (OR, 2.16; 1.9–2.46; p<0.001) and broad-spectrum penicillins (OR, 1.44; 1.26–1.61; p<0.001) within 3–6 months of the index date showed the highest risk.

Risk from exposure 6–12 months prior to diagnosis was lower, but remained significant: sulfas (OR, 2.16; 1.92–2.22; p<0.001), cephalosporins (OR, 1.7; 1.57–1.84; p<0.001), fluoroquinolones (OR, 1.59; 1.44–1.75; p<0.001), nitrofurantoins (OR, 1.69; 1.51–1.9; p<0.001) and broad-spectrum penicillins (OR, 1.21; 1.11–1.32; p<0.001).

The effect of all five oral antibiotic classes on the risk of nephrolithiasis development remained significant even when exposure was 3–5 years prior to diagnosis.

The present findings indicate that oral antibiotics likely contribute to the increased formation of calcium-based calculi, as most of the nephrolithiasis cases in industrialized countries involve stones of such composition, said researchers.

“One potential mechanism is that antibiotics change composition of the intestinal microbiome and consequently alter macronutrient metabolism,” they explained, adding that antibiotics may also promote the domination of multidrug resistant bacteria in the urinary microbiome, leading to stone formation. [Nephrol Dial Transplant 2012;27:4125-4130; Cell 2014;158:705-721]

“Future studies should examine the underlying microbial biomolecular mechanisms and change in intestinal metabolic products caused by different antibiotics,” they said.

Researchers performed a population-based, nested case-control study including 25,981 nephrolithiasis patients and 259,797 controls (34.9 percent female for both groups). Information on oral antibiotic prescriptions during the 3–12-month primary exposure period was retrieved from The Health Improvement Network database.

In the context of the recent rise in the prescription and administration of antibiotics, “[o]ur findings support the hypothesis that antibiotics may be contributing to the increasing prevalence and earlier age at onset of nephrolithiasis,” said researchers.

“Given that children receive more antibiotics than any other age group, and 3 percent of antibiotics prescribed during ambulatory care visits are inappropriate, these findings provide another reason to reduce inappropriate outpatient antibiotic use,” they added. [JAMA 2002;287:3133-3135; N Engl J Med 2013;368:1461-1462; JAMA 2016;315:1864-1873]

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Most Read Articles
Prof. Cheuk-Chun Szeto, Dr. Winston W. S. Fung, 25 Jan 2018
A 65-year-old lady with a background of type 2 diabetes, hyperlipidaemia and chronic immune thrombocytopenia presented to us with a 2-week history of generalized malaise and myalgia. Shortly after the onset of myalgia, she was noted to have reduced urine output and the urine was described as dark in colour. Her regular medications included prednisolone, danazol, simvastatin, metformin, and human insulin. Upon further questioning, the patient admitted that her compliance to simvastatin and danazol used to be poor. However, she recently started to take both medications regularly after repeated education.
Pearl Toh, 30 Jan 2018
Use of statins may not be neuroprotective, in contrast to findings from previous observational studies. On the contrary, fungus-derived or lipophilic statins appeared to be associated with a slightly increased risk of Alzheimer's disease (AD) compared with synthetic and hydrophilic statins, suggests a new study based on real-world clinical practice data.
26 Dec 2017
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Rachel Soon, 21 Feb 2018

MIMS Pharmacist sits down with pharmacist researcher Dr Mai Chun Wai to find out more about his work in drug discovery, including his investigations of Antarctic soil microorganisms.