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Diversity of the midstream urine microbiome in adults with chronic kidney disease
Authors:Holly Kramer  Gina Kuffel  Krystal Thomas-White  Alan J. Wolfe  Kavitha Vellanki  David J. Leehey  Vinod K. Bansal  Linda Brubaker  Robert Flanigan  Julia Koval  Anuradha Wadhwa  Michael J. Zilliox
Affiliation:1.Department of Public Health Sciences,Loyola University Chicago,Maywood,USA;2.Medicine, Division of Nephrology and Hypertension,Loyola University Chicago,Maywood,USA;3.Departments of Microbiology and Immunology,Loyola University Chicago,Maywood,USA;4.Obstetrics and Gynecology,Loyola University Chicago,Maywood,USA;5.Urology, Stritch School of Medicine,Loyola University Chicago,Maywood,USA;6.Hines VA Medical Center,Hines,USA;7.Evy Health,Menlo Park,USA;8.Department of Reproductive Medicine, Division of Female Pelvic Medicine and Reconstructive Surgery,University of California San Diego,La Jolla,USA
Abstract:

Purpose

To examine the characteristics of the midstream urine microbiome in adults with stage 3–5 non-dialysis-dependent chronic kidney disease (CKD).

Methods

Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR]?2) and diuretic use were recruited from outpatient nephrology clinics. Midstream voided urine specimens were collected using the clean-catch method. The bacterial composition was determined by sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene. Extraction negative controls (no urine) were included to assess the contribution of extraneous DNA from possible sources of contamination. Midstream urine microbiome diversity was assessed with the inverse Simpson, Chao and Shannon indices. The diversity measures were further examined by demographic characteristics and by comorbidities.

Results

The cohort of 41 women and 36 men with detectable bacterial DNA in their urine samples had a mean age of 71.5 years (standard deviation [SD] 7.9) years (range 60–91 years). The majority were white (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR was 27.2 (SD 13.6) ml/min/1.73 m2. Most men (72.2%) were circumcised and 16.6% reported a remote history of prostate cancer. Many midstream voided urine specimens were dominated (>?50% reads) by the genera Corynebacterium (n?=?11), Staphylococcus (n?=?9), Streptococcus (n?=?7), Lactobacillus (n?=?7), Gardnerella (n?=?7), Prevotella (n?=?4), Escherichia_Shigella (n?=?3), and Enterobacteriaceae (n?=?2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P?

Conclusions

The midstream voided urine microbiome of older adults with stage 3–5 non-dialysis-dependent CKD is diverse. Greater microbiome diversity is associated with higher eGFR.
Keywords:
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