Clinical trial NCT04686318: Accuracy of Infection Biomarkers in the Investigation of Patients With Suspected Acute Pyelonephritis
Official title: What is the Diagnostic and Prognostic Accuracy of C-reactive Protein, Serum Procalcitonin and Soluble Urokinase Plasminogen Activator Receptor in the Initial Investigation of Patients With Suspected Acute Pyelonephritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Pyelonephritis
Keywords: C-reactive protein
serum procalcitonin
soluble urokinase plasminogen activator receptor
diagnostic and prognostic markers
emergency department
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2020-12-28
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Acutely admitted patients with suspected Acute pyelonephritis (APN) from three emergency departments (EDs) in the Region of Southern Denmark (Hospital Sønderjylland, Hospital Lillebælt, Odense University Hospital)

Brief summary: The aim of this study is to investigate the diagnostic and prognostic value of C-reactive protein (CRP), serum procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) in the initial investigation of patients hospitalized with suspected acute pyelonephritis (APN).

Detailed description: Acute pyelonephritis (APN) is a severe acute infection in the upper urinary tract, which quite frequently is seen in the emergency department (ED). In our study, we define APN as a urinary tract infection with extension above the bladder, implicated by systemic affection in a suspected urinary tract infection (ie, fever, chills, malaise and/or lethargy beyond normal, signs of sepsis). Most often, an infection of the bladder ascends to the kidneys, causing APN. Symptoms and clinical affection range from mild to severe, but it is always important to recognize and treat APN fast in order to prevent progression to sepsis, renal failure and ultimately death. Uncertain or delayed diagnosis will often lead to an overconsumption of broad-spectrum antibiotics, which contributes to increased development of resistant bacteria and thus threaten the treatment options of the future.

APN diagnosis is primarily made today on the basis of clinical symptoms and findings in the form of flank tenderness, fever and nausea/vomiting. Typical symptoms of cystitis (dysuria, pollakisuria, suprapubic pain, hematuria) are possible but often absent. Especially elderly can present with more generalized signs of infection with nothing clearly indicating localization to the urinary tract. A positive urine culture verifies the diagnosis, but it is only available after a minimum of 24 hours.

To support the diagnosis of an APN and assess its severity, a measure of the systemic inflammatory response is useful such as abnormal temperature, elevated leucocyte count with neutrocytosis, or elevated C-reactive protein (CRP). Some uncertainty is associated with CRP because it has a delayed response to bacterial infection and is often elevated in non-infectious inflammatory conditions. A more sensitive and specific marker is desired that can differentiate between bacterial and viral infection and reflect the severity of the APN. Serum procalcitonin (PCT) has potential as a diagnostic tool in suspected bacterial infections and can distinguish between viral and bacterial urinary infections. Soluble urokinase plasminogen activator receptor (SuPAR) might have a potential as a marker for acute bacterial infections requiring antibiotic treatment. However, there are no well-conducted studies which compare simultaneously all three biomarkers diagnostic abilities for bacterial infections in general or in relation to APN.

The investigators hypothesize that serum CRP, PTC and suPAR have an impact on diagnosing, prognosis, and treatment of patients with a verified APN.

The objectives of the study are:

* To investigate the diagnostic value of CRP, PCT and suPAR in the diagnosis of APN
* To identify the prognostic value of CRP, PCT and suPAR in relation to adverse events in patients with verified APN

Eligibility criteria: Inclusion Criteria:

* Suspicion of APN assessed by the receiving physician at the ED

Exclusion Criteria:

* If the attending physician considers that participation will delay a life-saving treatment or patient needs direct transfer to the intensive care unit.
* Admission within the last 14 days
* Verified COVID-19 disease within 14 days before admission
* Pregnant women
* Severe immunodeficiencies: Primary immunodeficiencies and secondary immunodeficiencies (HIV positive CD4 \<200, Patients receiving immunosuppressive treatment (ATC L04A), Corticosteroid treatment (\>20 mg/day prednisone or equivalent for \>14 days within the last 30 days), Chemotherapy within 30 days)

Primary outcomes:
measure: Verified and non verified acute pyelonephritis (APN)
timeFrame: 2 months after patient discharge
Secondary outcomes:
measure: Intensive care unit treatment
timeFrame: within 60 days from admission to the emergency department
measure: Length of stay
timeFrame: within 60 days from current admission to the emergency department
measure: The number of participants who died within 30 days
timeFrame: within 30 days from arrival day
measure: The number of participants who died within 90 days
timeFrame: within 90 days from arrival to emergency department
measure: Readmission
timeFrame: within 30 days from day of discharge
measure: In-hospital mortality
timeFrame: within 60 days from admission to the emergency department
Other outcomes:
measure: Bacteriuria
timeFrame: urine collected within 4 hours of arrival to the emergency department
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
Study officials:
affiliation: Hospital of Southern Jutland
name: Christian Backer Mogensen
role: STUDY_CHAIR
References:
citation: Hamie L, Daoud G, Nemer G, Nammour T, El Chediak A, Uthman IW, Kibbi AG, Eid A, Kurban M. SuPAR, an emerging biomarker in kidney and inflammatory diseases. Postgrad Med J. 2018 Sep;94(1115):517-524. doi: 10.1136/postgradmedj-2018-135839. Epub 2018 Sep 3.
citation: Schuetz P, Christ-Crain M, Muller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype? Swiss Med Wkly. 2009 Jun 13;139(23-24):318-26. doi: 10.4414/smw.2009.12584.
citation: Skjot-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Hertz MA, Graumann O, Rosenvinge FS, Petersen ERB, Ostergaard C, Laursen CB, Skovsted TA, Posth S, Chen M, Mogensen CB. Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study. BMJ Open. 2021 Sep 30;11(9):e049606. doi: 10.1136/bmjopen-2021-049606.