Kidney Week

Abstract: SA-OR007

Gut Microbiota Dysbiosis Is a Novel Risk Factor for Urinary Tract Infections in Kidney Transplant Recipients

Session Information

• Access, Organ Utilization, and Infectious Disease
  October 27, 2018 | Location: 24A, San Diego Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Lee, John Richard, Weill Cornell Medicine, New York, New York, United States

John Richard Lee, MD, MS, FASN



I am a transplant nephrologist at Weill Cornell Medicine and an academic physician scientist with expertise in translational microbiome research studies. I am currently funded by a K23 career development award from the NIH / NIAID (2016) and an R21 exploratory/development award from the NIH / NIAID (2017). My laboratory's current focus is establishing the relationship between the microbiome and complications in patients with kidney disease as well as kidney transplant recipients.

• Magruder, Matthew, Weill Cornell Medicine, New York, New York, United States

Matthew Magruder,

• Sholi, Adam N., Weill Cornell Medicine, New York, New York, United States

Adam N. Sholi,

• Edusei, Emmanuel Y., Weill Cornell Medicine, New York, New York, United States

Emmanuel Y. Edusei,

• Zhang, Lisa T., Weill Cornell Medicine, New York, New York, United States

Lisa T. Zhang,

• Albakry, Shady Y., Weill Cornell Medicine, New York, New York, United States

Shady Y. Albakry,

• Lubetzky, Michelle L., Weill Cornell Medicine, New York, New York, United States

Michelle L. Lubetzky,

• Dadhania, Darshana, Weill Cornell Medicine, New York, New York, United States

Darshana Dadhania,

• Taur, Ying, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Ying Taur,

• Ling, Lilan, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Lilan Ling,

• Burnham, Philip, Cornell University, Ithaca, New York, United States

Philip Burnham,

• De Vlaminck, Iwijn, Cornell University, Ithaca, New York, United States

Iwijn De Vlaminck,

• Pamer, Eric, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Eric Pamer,

• Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States

Manikkam Suthanthiran,

Background

The gut is the presumed source of urinary tract infection (UTI) but direct evidence for this supposition is lacking.

Methods

We recruited 169 kidney transplant recipients for serial collection of fecal specimens and profiled 516 fecal specimens using 16S rRNA gene deep sequencing of the V4-V5 hypervariable region. Among the cohort, 36 subjects developed Escherichia bacteriuria within the first 6 months of transplantation (Escherichia Group) and 133 subjects did not (No Escherichia Group); 36 subjects developed Enterococcus bacteriuria (Enterococcus Group) and 133 subjects did not (No Enterococcus Group).

Results

The relative gut abundance of Escherichia was significantly higher in the fecal specimens in the Escherichia Group than in those in the No Escherichia Group (P<0.001, Wilcoxon rank sum test) (Fig 1A) and the relative gut abundance of Enterococcus was significantly higher in the fecal specimens in the Enterococcus Group than in those in the No Enterococcus Group (P<0.001) (Fig 1B). Using a Cox Regression with gut abundance as a time-dependent covariate, a relative gut abundance of 1% Escherichia was a risk factor for future development of Escherichia bacteriuria (HR= 3.2, P<0.001), and a relative gut abundance of 1% Enterococcus was a risk factor for future development of Enterococcus bacteriuria (HR = 2.6, P= 0.006). Strain analysis of the Escherichia coli in paired urine-fecal specimens using shotgun metagenomic sequencing revealed that the E. coli strain in the urine specimens was most similar to the E. coli strain in the fecal specimens from the same subject, supporting the gut as the source of the urine strain (Fig 1C).

Conclusion

Our findings support the hypothesis that gut microbial composition is a contributor to UTI in kidney transplant recipients. Modulating the gut microbiota may be a novel and effective strategy for preventing this frequent complication.

Funding

• Other NIH Support