Accuracy of Infection Biomarkers in the Investigation of Patients With Suspected Acute Pyelonephritis

• ClinicalTrials.gov Identifier: NCT04686318
• Recruitment Status: Recruiting
• First Posted: December 28, 2020
• Last Update Posted: November 29, 2021
• Sponsor: University of Southern Denmark
• Information provided by (Responsible Party): University of Southern Denmark

Study Description

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).

Condition or disease	Intervention/treatment
Acute Pyelonephritis	Diagnostic Test: Biomarkers for acute pyelonephritis

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

Study Design

• Study Type: Observational
• Estimated Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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
• Actual Study Start Date: March 1, 2021
• Estimated Primary Completion Date: March 2022
• Estimated Study Completion Date: July 2022

Groups and Cohorts

Group/Cohort

Intervention/treatment

suspected acute pyelonephritis; All patients admitted to the emergency department with suspected acute pyelonephritis assessed by the receiving physician

Diagnostic Test: Biomarkers for acute pyelonephritis; Blood samples will be collected by a medical laboratory technologist and transferred to the local laboratory for analysis of CRP, PCT and suPAR. Laboratory staff will be blinded to participant diagnosis and outcome. CRP and PCT results will be available to the treating physician, but the suPAR result will not be available.; Diagnostic test of CRP. CRP will be measured using an immunoturbidimetric assay (Tina-quant®, Roche) on Roche/Hitachi Cobas© systems.; Diagnostic test of PCT: Plasma PCT will be quantified by an automated sandwich immunoassay "ECLIA" (Elecsys®, BRAHMS PCT-analyses) on Cobas© within two hours from collection according to standard procedure.; Diagnostic test of suPAR: Plasma suPAR will be quantified by using the commercial available suPARnostic© Tubilatex assay reagents (ViroGates, Denmark) on Cobas© as previously validated (35). Separated plasma is kept refrigerated and analysed for suPAR within 48 hours after collection.

Outcome Measures

Primary Outcome Measures :

1. Verified and non verified acute pyelonephritis (APN) [ Time Frame: 2 months after patient discharge ]
   The decision of whether patients admitted with suspicion of APN actually has a final diagnosis of APN is based on a combination of all findings during admission. The verification of diagnosis requires human handling, interpretation and judgment. Therefore, in this study, an expert panel will define the reference standard for the diagnosis APN. The expert panel consists of two independent consultants from the emergency department with significant experience in emergency medicine and acute infections. They will individually determine whether or not the patient admitted suspected with APN actually had this diagnosis. The final diagnosis will be based on all available relevant information from the patient medical record including MRI of the kidneys. A standardized template will be used. Disagreement will be discussed until a consensus is reached.

Secondary Outcome Measures :

1. Intensive care unit treatment [ Time Frame: within 60 days from admission to the emergency department ]
   transfer to ICU during current admission (binary outcome)
2. Length of stay [ Time Frame: within 60 days from current admission to the emergency department ]
   days spent in hospital during current admission
3. The number of participants who died within 30 days [ Time Frame: within 30 days from arrival day ]
   binary - 30-days mortality
4. The number of participants who died within 90 days [ Time Frame: within 90 days from arrival to emergency department ]
   binary - 90 days mortality
5. Readmission [ Time Frame: within 30 days from day of discharge ]
   binary
6. In-hospital mortality [ Time Frame: within 60 days from admission to the emergency department ]
   binary

Other Outcome Measures:

1. Bacteriuria [ Time Frame: urine collected within 4 hours of arrival to the emergency department ]
   Binary outcome defined by microbiologist on urine culture analysis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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)

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)

Contacts and Locations

Contacts

Contact: Helene Skjøt-Arkil, PhD; +45 79971113; Helene.Skjoet-Arkil@rsyd.dk

Contact: Christian Backer Mogensen; +45 79971123; Christian.Backer.Mogensen@rsyd.dk

Locations

Denmark

Hospital of Southern Jutland; Recruiting

Aabenraa, Denmark

Contact: Christian B Mogensen, MD

Sponsors and Collaborators

University of Southern Denmark

Investigators

• Study Chair: Christian Backer Mogensen; Hospital of Southern Jutland

More Information

Publications:

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. Review.

Schuetz P, Christ-Crain M, Müller 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: smw-12584. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Skjøt-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Hertz MA, Graumann O, Rosenvinge FS, Petersen ERB, Østergaard 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.

• Responsible Party: University of Southern Denmark
• ClinicalTrials.gov Identifier: NCT04686318
• Other Study ID Numbers: SHS-ED-12c-2020
• First Posted: December 28, 2020
• Last Update Posted: November 29, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Southern Denmark:

C-reactive protein; serum procalcitonin; soluble urokinase plasminogen activator receptor; diagnostic and prognostic markers; emergency department

Additional relevant MeSH terms:

Pyelonephritis; Nephritis, Interstitial; Nephritis; Kidney Diseases; Urologic Diseases; Pyelitis