Medical Professional Publications

Bacteria Are Present in Kidney Stones and May Contribute to Their Formation

Columbus, OH - March 2016

A study led by researchers at Nationwide Children’s Hospital has made a series of findings about the interaction between calcium oxalate (CaOx) kidney stones and uropathogenic bacteria – and may point toward an explanation of why kidney stones form.

Experiments performed in vitro and in vivo in murine models ultimately showed:

  • Bacteria can be identified in CaOx kidney stones by use of DNA sequencing;
  • In a mouse model, CaOx deposits increase the number of bacteria that remain in the kidney after an experimental kidney infection is induced;
  • In turn, uropathogenic E. coli (UPEC) inoculation increases CaOx deposits;
  • CaOx deposits and bacteria conglomerations induce a renal innate immune response not triggered by either substance alone;
  • The immune proteins produced from this response may form a matrix allowing a crystal to expand into a kidney stone.

“We cannot say yet if bacteria are crucial for the formation of CaOx kidney stones,” says Andrew L. Schwaderer, MD, senior author of the study and research director for the Section of Nephrology at Nationwide Children’s. “However, using new technology, we have demonstrated that bacteria are in kidney stones. Their interaction may help explain why kidney stones form, and why patients with kidney stones are at increased risk for urinary tract infections."

The study, published in the journal PLoS One, determined as a first step whether bacteria were present in human CaOx kidney stones. Five pediatric patients with kidney stones were enrolled at Nationwide Children’s. Gene sequencing found bacterial DNA in the stones of all five patients; four had bacteria from the Enterobacteriaceae family. E. coli is a member of that family, which led researchers to focus on that bacteria’s interaction with CaOx deposits in mice.  Previously, bacteria in kidney stones could only be identified if grown in culture. 

UPEC selectively aggregated on and around CaOx monohydrate crystals in significant numbers in vitro. Subsequent analysis after CaOx induction and UPEC inoculation in mice indicated that one tended to amplify the other.

Kidney CaOx deposits alone upregulated 12 of 83 innate immune genes involved with inflammation, toll-like receptor signaling and inflammasome formation. When mice were inoculated with both CaOx and UPEC, certain inflammatory genes and stone matrix protein genes were elevated, along with one toll-like receptor gene.

According to Dr. Schwaderer, it is possible that kidney stones or CaOx crystalluria are a risk factor for pyelonephritis, and may be screened for in patients with recurrent infections. But this research points to many other possible avenues of study, including the characterization of the kidney stone microbiome and the mechanisms responsible for the interaction between bacteria and CaOx deposits.

Reference:
Barr-Beare E, Saxena V, Hilt EE, Thomas-White K, Schober M, Li B, Becknell B, Hains DS, Wolfe AJ, Schwaderer AL. The interaction between enterobacteriaceae and calcium oxalate deposits. PloS One. 2015 Oct 8;10(10): e0139575.

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