Heparin-Binding Protein: A Diagnostic Biomarker of Urinary Tract Infection in Adults

Abstract

Background. Urinary tract infections (UTIs) are associated with significant morbidity and high frequency of antibiotic prescription. Diagnosing UTI is often difficult, particularly in the critically ill patient and in patients with unspecific and mild symptoms. The standard rapid tests have limited value, and there is a need for more reliable diagnostic tools. Heparin-binding protein (HBP) is released from neutrophils and has previously been studied as a diagnostic and predictive biomarker in different bacterial infections.Methods. This prospective survey enrolled adult patients at 2 primary care units and 2 hospital emergency departments, to investigate in urine HBP as a biomarker of UTI. In addition, urine levels of interleukin-6, white blood cells, and nitrite were analyzed and compared with HBP. Based on symptoms of UTI and microbiological findings, patients were classified into different groups, UTI (cystitis and pyelonephritis) and no UTI.Results. Three hundred ninety patients were evaluated. The prevalence of UTI in the study group was 45.4%. The sensitivity and specificity for HBP in urine as a marker for UTI were 89.2% and 89.8%, respectively. The positive and negative predictive values were 90.2% and 88.8%, respectively. Heparin-binding protein was the best diagnostic marker for UTI, with an area-under-curve value of 0.94 (95% confidence interval, 0.93–0.96). Heparin-binding protein was significantly better in distinguishing cystitis from pyelonephritis, compared with the other markers.Conclusions. An elevated level of HBP in the urine is associated with UTI and may be a useful diagnostic marker in adult patients with a suspected UTI.

Predictive value of urinary interleukin‐6 for symptomatic urinary tract infections in a nursing home population

“…In the mentally deteriorated and multidiseased elderly population with a high prevalence of ABU, it is not possible to use this diagnostic standard . Studies available, including the present study, identify IL‐6 to be the most interesting marker candidate differentiating between ABU and UTI . Further studies should test, by close safety monitoring, the concept of IL‐6 as a marker for treatment indication or a wait‐and‐see approach in suspected UTI.…”

“…Both markers were significantly elevated in patients with UTI as compared with patients without UTI. 16 IL-6 was inferior in regard to sensitivity and specificity, but there was no comparison between patients with UTI and ABU only. 16 The present results show urine IL-6 to be the most promising marker of an objective UTI diagnosis in patients with an ongoing inflammatory response caused by ABU.…”

“…A recent study analyzed urinary concentrations of IL‐6 and heparin binding protein, a protein secreted from activated neutrophils. Both markers were significantly elevated in patients with UTI as compared with patients without UTI . IL‐6 was inferior in regard to sensitivity and specificity, but there was no comparison between patients with UTI and ABU only …”

“…These efforts have reduced antibiotic treatments, but with the interventional effect decreasing over time . Obviously, as well as improved clinical standards, the introduction of new diagnostic biomarkers, distinguishing ABU not requiring treatment from symptomatic UTI, are needed …”

“…14 Obviously, as well as improved clinical standards, the introduction of new diagnostic biomarkers, distinguishing ABU not requiring treatment from symptomatic UTI, are needed. 16,17 Active bacterial infection in the lower urinary tract initiates a local inflammatory response including epithelial release of cytokines, such as IL-6 and IL-8, acting as neutrophil chemoattractants, acute phase response activators and endogenous pyrogens. 18,19 The interaction between the host defenses, influenced by genetic polymorphism, and the bacterial virulence decides the outcome of the infection.…”