SUFU 2019: Voiding Behavior Changes in a Murine Model of Chronic UTI is Correlated to Urinary Bacterial Load and Inflammatory Cytokines/Chemokines

Miami, FL (UroToday.com) Toby Chai, MD, and colleagues presented their model for chronic UTI, they used murine model inoculating C57BL/6 female mouse, aged 10 weeks old, with uropathogenic E. coli (UPEC,10^8 CFU/50 μl) two times, 24 hours apart. Chronicity of UTI was defined by urine CFU ≥10^4 CFU at 28 days post-infection (dpi). 14 mice were used in this study. At 28 dpi, UPEC loads in urine, bladder and kidney specimens were measured by culture CFUs. Cytokines/chemokines levels in urine, bladder and kidney specimens were measured with 32-plex ELISA. Linear regression correlations between 4- hour voiding spot assay (VSA) parameters with #1. UPEC loads (in urines, bladders, kidneys) and #2. cytokines/chemokines levels (in urines, bladders, kidneys) were performed.

They found that there was increasing urine CFU was significantly correlated with increasing total spot volume (R=0.747, p=0.002), total spot volume outside (R=0.756, p=0.002), total volume/total spot (R=0.545, p=0.044), and the number of primary void spots (R=0.95, p<0.001). Increasing bladder CFU was significantly correlated with increasing total spot volume (R=0.709, p=0.005), total spot volume outside (R=0.725, p=0.003), total volume/total spot (R=0.639, p=0.014), and number of primary void spots (PVS) (R=0.766, p=0.001). Increasing kidney CFU was significantly correlated with a total number of spots outside (0.669, p=0.009), and a number of primary void spots (R=0.630, p=0.016). RANTES, MIP-Ib, IL-17, IP-10, KC, MCP-1, MIP-2, M-CSF in different specimens were significantly correlated with voiding behavior changes. Select significant correlations of urinary UPEC load (CFU) and urinary IP-10 with various VSA parameters are shown in the Figure.

UroToday SUFU2019 Voiding Behavior Changes

At the end of the presentation, they concluded that increasing bacterial load and inflammatory cytokines (RANTES, MIP-Ib, IL-17, IP-10, KC, MCP-1, MIP-2, M-CSF) in urine, bladder, and kidney are significantly correlated with bladder voiding behavior changes (towards overactive voiding behavior) in a murine chronic UTI model. They also report that these could help in understanding how objective parameters (bacterial load and cytokine/chemokines) correlate with overactive voiding behavior in chronic UTIs. Treatment of LUTS in chronic UTI status could target changes in these cytokines/chemokines.

Presented by: Toby Chai, MD, Yale School of Medicine, Department of Urology, New Haven, CT

Co-Authors: Kejia Zhu, MD,¹ Patrick Popiel, MD,² Warren Hill, PhD³
Author Affiliation:
1. Qilu Hospital of Shandong University, Jinan Shi, Shandong Sheng, China
2. Yale School of Medicine, Department of Ob/Gyn/Reproductive Sciences, New Haven, Connecticut
3. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Written by: Bilal Farhan, MD, Clinical Instructor, Female Urology and Voiding Dysfunction, Department of Urology, University of California, Irvine, @Bilalfarhan79, at the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting, SUFU 2019, February 26 - March 2, 2019, Miami, Florida

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