Asymptomatic bacteriuria (ASB) is the isolation of a specified quantity of bacteria from a person without symptoms or signs referableto urinary infection. ASB is common in women and increases with advancing age. There is some evidence that treatment of ASB does not prevent symptomatic urinary tract infection (UTI) and may actually lead to an increased incidence of uropathogen antibiotic resistance with a higher likelihood of complications. Questions remain as to incidence of ASB in the renal transplant recipient and whether certain virulence factors expressed on uropathic bacteria facilitate symptomatic UTI or acute renal allograft injury. In preliminary retrospective studies, we found that the majority of renal transplant patients with E. coli UTI are asymptomatic. Despite the lack of UTI symptoms, some renal transplant patients with ASB develop cystitis, pyelonephritis or acute kidney injury. The majority of the bacterial isolates from ASB patients with renal allograft injury express uropathic P fimbriae, an adhesin molecule that facilitates bacterial attachment to the uro-epithelium and may contribute to an injurious inflammatory immune response. In addition, the urinary isolates from renal transplant patients with E. coli ASB are frequently resistant to common antimicrobial agents used to treat UTI. We propose to determine the prevalence of ASB in renal transplant patients and to identify the host characteristics and bacterial virulence factors expressed on ASB isolates that facilitate the develop of symptomatic UTI. Identifying isolates from patients with ASB that express uropathogenic factors will limit inappropriate antibiotic use and decrease the deleterious effects of UTI on renal allograft function. The ultimate goal of this line of research is to determine if screening and treatment of ASB prevents symptomatic UTI and prevents renal allograft injury. Data from this R21 pilot grant will be the background for the design of a multi-center clinical trial of ASB in the renal transplant patient. Information from this trial would lead to a much needed screening and treatment guidelines for ASB in the renal transplant population.

Public Health Relevance

Urinary tract infections (UTIs) are the most common infection in the kidney transplant patient and are associated with a poor kidney graft and patient survival. It is unclear if asymptomatic UTI, or asymptomatic bacteriuria (ASB), is associated with the development of symptomatic UTI or graft dysfunction in the renal transplant patient. Recent guidelines from the Infectious Disease Society of American (IDSA) acknowledge that """"""""no recommendations can be made for or against screening or treatment of ASB in renal transplant patients"""""""". Studies are needed to determine the prevalence of ASB and the host characteristics, bacterial virulence factors and consequences associated with ABU in the renal transplant patient.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DK077960-02
Application #
8055156
Study Section
Special Emphasis Panel (ZRG1-RUS-F (51))
Program Officer
Flessner, Michael Francis
Project Start
2009-09-21
Project End
2011-08-31
Budget Start
2009-11-01
Budget End
2010-08-31
Support Year
2
Fiscal Year
2009
Total Cost
$277,658
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037