Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women

Ebrahimzadeh, Tahmineh; Kuprasertkul, Amy; Neugent, Michael L.; Lutz, Kevin C.; Fuentes, Jorge L.; Gadhvi, Jashkaran; Khan, Fatima; Zhang, Cong; Sharon, Belle M.; Orth, Kim; Li, Qiwei; Nisco, Nicole J. De

doi:10.26508/lsa.202000948

Cited by 11 publications

(32 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on these findings, Ebrahimzadeh and colleagues ( 72 ) assessed urinary prostaglandin E2 (PGE2), which is a product of arachidonic acid conversion by the COX-2 enzyme, as a biomarker for rUTI in a cohort of 92 postmenopausal women (31 women with acute UTI and a rUTI history, 35 women with rUTI but without an active infection and 26 healthy controls). They found a positive association between urinary PGE2 concentration and urothelial COX-2 expression.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

Hosman

Roić²,

Lamot³

2022

Front. Med.

View full text Add to dashboard Cite

Recurrent urinary tract infections (rUTI) represent a major healthcare and economic burden along with a significant impact on patient’s morbidity and quality of life, even in the absence of well-known risk factors, such as vesicoureteral reflux. Despite numerous attempts to find a suitable therapeutic option, there is no clear benefit of any currently available intervention for prevention of UTI recurrence and its long-term consequences such as hypertension, renal scarring and/or insufficiency. The common treatment practice in many centers around the globe involves the use of continuous low-dose antibiotic prophylaxis, irrespective of various studies indicating increased microbial resistance against the prophylactic drug, leading to prolonged duration and escalating the cost of UTI treatment. Moreover, the rapid appearance of multi-drug resistant uropathogens is threatening to transform UTI to untreatable disease, while impaired host-microbiota homeostasis induced by a long-term use of antibiotics predisposes patients for various autoimmune and infectious diseases. New biomarkers of the increased risk of UTI recurrence could therefore assist in avoiding such outcomes by revealing more specific patient population which could benefit from additional interventions. In this light, the recent findings suggesting a crucial role of urothelial innate immunity mechanisms in protection of urinary tract from invading uropathogens might offer new diagnostic, prognostic and even therapeutic opportunities. Uroepithelial cells detect uropathogens via pattern recognition receptors, resulting in activation of intracellular signaling cascade and transcription factors, which ultimately leads to an increased production and secretion of chemokines, cytokines and antimicrobial peptides into the urinary stream. Emerging evidence suggest that the disturbance of a single component of the urinary tract innate immunity system might increase susceptibility for rUTI. The aim of the current review is to update clinicians and researchers on potential biomarkers of host immune response alterations predisposing for rUTI and propose those well worth exploring further. For this purpose, over a hundred original papers were identified through an extensive PubMed and Scopus databases search. This comprehensive review might enrich the current clinical practice and fill the unmet clinical needs, but also encourage the development of therapeutic agents that would facilitate urinary bacterial clearance by enhancing the host immune response.

show abstract

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

Hosman

Roić²,

Lamot³

2022

Front. Med.

View full text Add to dashboard Cite

show abstract

“…The physiologically relevant PGE2 level in human urine ranges from 500 to 5000 pg/mL. 23 Figure S9 shows the characteristic response curves for both EIS and MS methods. Calibrated sensor dose responses for PGE2 detection in synthetic urine (pH 6) are depicted in Figure S5.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…From literature, it has been found that urine PGE2 levels elevated above 2000 pg/mL are indicative of active rUTI in postmenopausal women and concentrations below this level are consistent with women who do not have active UTI or rUTI. 23 This threshold was utilized for spike and recovery analysis to evaluate the efficacy of dose-response experiments and the sensor's ability to distinguish between "no-UTI" and "active-UTI" cases (Figure 5). Thus, the signal response at PGE2 dose concentration of 2000 pg/mL was used as the threshold dose as the UTI classification threshold for classifying test urine sample as UTI positive or negative.…”

Section: T H Imentioning

confidence: 99%

“…Optical density measurements for these colorimetric assays were performed with a Syngergy H1 plate reader (Biotek, Winooski, VT). 23 Figure 7C shows the setup for carrying out these experiments. Postanalysis was done using the calibration doseresponse curves for both methods described in the previous sections.…”

Section: T H Imentioning

confidence: 99%

“…In their recent work, Ebrahimzadeh et al showed that urinary Prostaglandin E2 (PGE2) is one such biomarker that can serve not only as a reliable diagnostic but also a prognostic biomarker for rUTI in postmenopausal women. 23 PGE2, which is an enzymatic product of cyclooxygenase-2 (COX-2), is a critical mediator of the inflammatory response. 24,25 Thus, PGE2 was chosen as the target biomarker to achieve early, accurate single number quantitative readouts, independent of the causative pathogen.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Label-Free, Novel Electrofluidic Capacitor Biosensor for Prostaglandin E2 Detection toward Early and Rapid Urinary Tract Infection Diagnosis

et al. 2021

Self Cite

View full text Add to dashboard Cite

Urine Prostaglandin E2 (PGE2) has been identified as an attractive diagnostic and prognostic biomarker for urinary tract infection (UTI). This work demonstrates the use of PGE2 as a biomarker for rapid and label-free testing for UTI. In this work, we have developed a novel electrofluidic capacitor-based biosensor that can used for home-based UTI management with high accuracy in less than 5 min for small volume urine samples (<60 μL). The PGE2 biosensor works on the principle of affinity capture using highly specific monoclonal PGE2 antibody and relies on non-faradaic electrical impedance spectroscopy (EIS) and Mott−Schottky (MS) for quantifying subtle variations in PGE2 levels expressed in human urine (pH 5−8). Dynamic light scattering experiments were performed to characterize surface charge properties and the impact of bulk interferents on the interfacial modulation of electrical properties due to binding and urine pH variations. Binding chemistry between the key elements of the immunosensor stack was validated using attenuated total reflectance-Fourier transform infrared spectroscopy and surface plasmon resonance studies. Linear calibration dose responses were obtained for PGE2 for both EIS and MS. The sensor reliably distinguished between UTI negative and UTI positive cases for both artificial (pH 5−8) and pooled human urine samples. The sensor was not found to cross-react with Prostaglandin D2, a structurally similar interferent, and other abundant urine interferents (urea and creatinine). Human subject studies confirmed the validity of the sensor for robust and accurate UTI diagnosis. This work can be extended to achieve easy, reliable, and rapid home-based UTI management, which can consequently help physicians with timely and appropriate administration of therapy to improve patient outcomes and treatment success.

show abstract

DigEST: Digital plug‐n‐probe disease Endotyping Sensor Technology

Ganguly

Ebrahimzadeh

Komarovsky

et al. 2022

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

In this work, we propose a novel diagnostic workflow-DigEST-that will enable stratification of disease states based on severity using multiplexed point of care (POC) biosensors. This work can boost the performance of current POC tests by enabling clear, digestible, and actionable diagnoses to the end user. The scheme can be applied to any disease model, which requires time-critical disease stratification for personalized treatment. Here, urinary tract infection is explored as the proof-ofconcept disease model and a four-class classification of disease severity is discussed.Our method is superior to traditional enzyme-linked immunosorbent assay (ELISA) as it is faster and can work with multiple disease biomarkers and categorize diseases by endotypes (or disease subtype) and severity. To map the nonlinear nature of biochemical pathways of complex diseases, the method utilizes an established supervised machine learning model for digital classification. This scheme can potentially boost the diagnostic power of current electrochemical biosensors for better precision therapy and improved patient outcomes.

show abstract

Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women

Cited by 11 publications

References 51 publications

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

Label-Free, Novel Electrofluidic Capacitor Biosensor for Prostaglandin E2 Detection toward Early and Rapid Urinary Tract Infection Diagnosis

DigEST: Digital plug‐n‐probe disease Endotyping Sensor Technology

Contact Info

Product

Resources

About