HK1180392B - Molecular markers for urinary tract infections - Google Patents
Molecular markers for urinary tract infections Download PDFInfo
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- HK1180392B HK1180392B HK13107403.1A HK13107403A HK1180392B HK 1180392 B HK1180392 B HK 1180392B HK 13107403 A HK13107403 A HK 13107403A HK 1180392 B HK1180392 B HK 1180392B
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- procalcitonin
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- urinary tract
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Description
Technical Field
The present invention relates to an in vitro method for determining the level of procalcitonin in plasma and urine as diagnostic marker to identify patients suffering from urinary tract infections, an in vitro method for performing said determination, a kit for diagnosing patients suffering from urinary tract infections, and the usefulness of procalcitonin in diagnosing urinary tract infections.
Background
Urinary Tract Infections (UTIs) are a very common problem, often associated with the use of urinary catheters (Hooton, TM, et al. Clin Infect dis.2010mar 1,50(5): 625-63), and are usually caused by saprophytic bacteria in the intestines and external genitalia, and in less common cases by fungi and viruses. These organisms can colonize the urinary tract via the urethra until reaching the bladder under certain conditions. Clinically, urinary infections are manifested by fever, dysuria, painful urinary dribbling, frequent micturition, urgency of urination, and moderate lower back pain.
The clinical symptoms are not necessarily sufficient to provide a diagnosis, especially in intensive care units where patients often cannot communicate their symptoms and various complications often mask the exact origin of the infection.
Therefore, laboratory testing is required for both isolation of the pathogens involved and for evaluation of any complications and identification of specific therapies.
Representative of alternative techniques for diagnosing urinary tract infections are urinary culture. This detection enables the isolation of the bacteria causing the infection and the evaluation of the sensitivity or resistance to antibiotics by antibiogram. The time required to obtain urine culture results varies between 24 and 48 hours, depending on the type of microorganism involved.
During waiting for results, empirical treatments based only on clinical observations are often performed, which can lead to inappropriate use of antibiotic therapy and patients who have undergone completely unnecessary (negative) urine cultures.
Therefore, it is very important to identify new tools for early diagnosis of UTI that are able to predict possible complications and improve outcomes, especially in certain "tricky" situations, such as in critically ill newborns or patients.
Disclosure of Invention
The present invention relates to in vitro methods and kits for diagnosing and/or monitoring urinary tract infections. The invention described herein is based on the discovery that the concentration of procalcitonin in a urine sample from a patient has a predictive value for diagnosing urinary tract infections. Furthermore, the inventors have observed that in patients suffering from urinary tract infections the concentration of procalcitonin in urine is greater than the concentration of procalcitonin in plasma, whereas in patients not affected by urinary tract infections the concentration of procalcitonin in urine is lower than the concentration of procalcitonin in plasma. Determination of the concentration of procalcitonin in urine can be used to diagnose the presence of urinary tract infections by comparing concentration values in the urine of a patient with standard values and/or on the basis of a proportional relationship between the plasma procalcitonin concentration and the procalcitonin concentration in urine.
The subject of the present invention is therefore an in vitro method for diagnosing and/or monitoring urinary tract infections, comprising a stage in which the concentration of procalcitonin in a urine sample of a patient is determined.
The subject of the present invention is also the above-mentioned method, which also comprises a phase in which the plasma procalcitonin concentration of said patient is also determined.
Subject of the present invention is also a kit for the in vitro diagnosis and/or monitoring and/or severity assessment of urinary tract infections, said kit comprising aliquots of the reagents necessary for determining the procalcitonin concentration in a urine sample and optionally a plasma sample.
The subject of the present invention is also the use of procalcitonin for the diagnosis and/or monitoring of urinary tract infections.
The present invention has the advantage that patients suffering from urinary tract infections can be diagnosed and/or monitored using very simple non-invasive methods and faster methods than those used in the technique known as urinary culture. Advantages, features, and methods of use of the present invention will become apparent from the following detailed description of certain embodiments, which is given by way of example and not of limitation.
Drawings
FIG. 1. population positive for urine culture. The figure shows the values of PCTur (urinary procalcitonin) and PCTpl (plasma procalcitonin) in 10 patients with urinary tract infections.
FIG. 2. urine culture negative population. The figure shows the values of PCTur (urinary procalcitonin) and PCTpl (plasma procalcitonin) in 10 patients without urinary tract infection.
Fig. 1 and 2 show that in the urine culture positive population, 9 out of 10 had a PCTur value greater than the PCTpl value, whereas in none of the patients belonging to the urine culture negative population, the PCTur value was greater than the PCTpl value.
Detailed Description
The present specification provides in vitro methods for diagnosing and/or monitoring urinary tract infections. The method of the invention makes it possible to diagnose and/or monitor urinary tract infections. The method of the invention makes it possible to diagnose the presence or absence of urinary tract infections, to assess (diagnose) the severity of the infection from a single assay (i.e. the higher the concentration of procalcitonin, the more severe the infection, the risk stratification at the first assay), and to monitor the progression of the infection during the treatment of the infection.
The term "urinary tract infection" in this specification refers to the invasion of a normally sterile urinary tract by a large number of microorganisms (bacteria, fungi and/or viruses) which determine the inflammatory response of the epithelium of the urinary tract.
Examples of microorganisms that can cause urinary tract infections are Escherichia coli (E.coli), Proteus Mirabilis (Proteus Mirabilis), Enterococcus faecalis (E.faecalis), Saprophyticus, Staphylococcus (Staphylococcus), Enterococcus (Enterococcus), Klebsiella (Klebsiella), Pseudomonas (Pseudomonas), Candida albicans (Candida albicans), and the like. Epidemiological data indicate that urinary tract infections are associated with the use of urinary catheters in one third of the cases. The invention is applicable to both patients with permanent or temporary urological medical devices (catheters, nephrostomy, cystostomy) and patients of all ages without these devices.
The method of the invention comprises a stage wherein the concentration of procalcitonin in a urine sample of a patient is determined. Procalcitonin (PCT) is a precursor of calcitonin, a hormone produced by medullary neuroendocrine C cells of the thyroid gland that is responsible for calcium homeostasis.
Advantageously, the method of the invention also comprises a stage during which the concentration of procalcitonin in the plasma sample of said patient is also determined. Not only is procalcitonin measured in urine, but also procalcitonin is measured in plasma, which makes it possible to diagnose the presence or absence of urinary tract infections more accurately in patients whose urine and plasma have been analyzed. In fact, clinical studies carried out by the inventors have shown that in all patients suffering from urinary tract infections the value of procalcitonin in urine is greater than the value of procalcitonin in plasma, whereas in negative patients the value is lower. This embodiment can be used, for example, in patients whose urinary procalcitonin values are insufficient to give a clear indication of the presence or absence of a urinary tract infection, or in patients presenting with a complex clinical situation (e.g., both urinary tract and systemic infections may be present).
Generally, for the determination of the concentration of procalcitonin in urine and/or plasma, any method known to the expert in the art that can be used for determining the concentration of procalcitonin in a biological fluid can be considered suitable for the purposes of the present description. For example, quantitative and semi-quantitative commercial immunoassays, e.g.PCT chemiluminescence,BRAHMSTRACE:BRAHMS PCT、The assay conditions may be modified to avoid possible interference by components of the urine matrix.
The concentration of procalcitonin in the urine and/or plasma sample to be tested is determined by incubating the sample for a suitable period of time and at a suitable temperature with a primary antibody specific for procalcitonin, which is suspended in a suitable buffer at a suitable concentration. The term antibody in this specification refers to an intact antibody or a fragment of an antibody; antibody fragments include, but are not limited to, fragment F (ab')2And Fab' or single chain antibodies.
For the purposes of the present specification, the term "primary antibody specific for procalcitonin" refers to any antibody capable of selectively binding to any part of procalcitonin.
Currently, the development of selective antibodies to specific proteins is performed using conventional techniques taught in laboratory manuals, and many companies also provide services for developing such antibodies. Thus, it is not necessary to provide further details in this specification regarding the production of antibodies, which may also be ordered from a suitable company.
Thus, in order to generate primary antibodies specific for procalcitonin, any standard technique will suffice for the development of both polyclonal and monoclonal antibodies. Furthermore, antibodies specific for procalcitonin are also commercially available (e.g. commercial antibodies, which can be used are those of Abcam, coded ab53897 (rabbit polyclonal), ab90489 (mouse monoclonal), ab24454 (HRP-linked mouse monoclonal), ab14817 (HRP-linked mouse monoclonal)) and can be used for the purposes of the present invention without further details being provided in the present description. Details regarding the primary antibody incubation protocol are well known to those skilled in the art and, if commercial antibodies are used, are given in the supplier's instructions. These incubation protocols include the use of suitable buffers, such as PBS (phosphate buffered saline) or buffers specifically recommended by the manufacturer if commercial antibodies are used.
For the detection of the primary antibody, the primary antibody may be labeled with any compound commonly used in antibody labeling selected from the following, and in particular cases, a fluorophore may be used: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL665 or an enzyme such as alkaline phosphatase or peroxidase.
Alternatively, if an indirectly labeled primary antibody is used, any labeled secondary antibody that selectively recognizes the primary antibody may be used to detect the primary antibody. As is known in the literature, the second antibody is specific for the constant region of the primary antibody, also known as the Fc portion, which in turn depends on the type of animal used when developing the primary antibody itself. In other words, it is the type of animal used to immunize with the epitope concerned (primary antibody) which defines the properties of the secondary antibody, and thus, for example, if the primary antibody is obtained from a rabbit, the secondary antibody is anti-rabbit; if the animal to be immunized is a sheep, then the second antibody is anti-sheep; if the primary antibody is developed in a mouse, the secondary antibody is a secondary anti-mouse antibody; and so on.
The second antibody may be labeled with any compound commonly used in antibody labeling selected from the following, and in particular cases, a fluorophore may be used: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL665 or an enzyme such as alkaline phosphatase or peroxidase.
In one embodiment, the concentration of procalcitonin can be determined using a primary antibody against procalcitonin, e.g., a polyclonal antibody linked to a fluorescent label, e.g., europium, and a secondary antibody against procalcitonin, which recognizes an epitope different from that recognized by the primary antibody, e.g., a monoclonal antibody linked to a fluorescent label, e.g., XL 665.
The method of the invention may be performed manually, or may be performed using any instrument known to those skilled in the art capable of performing the method automatically, e.g. a laboratory instrument such as kryptobrahms, or other methods for determining procalcitonin in plasma (e.g. such as）。
In one embodiment, the value of the concentration of procalcitonin in urine is compared to one or more values indicative for the presence or absence of a urinary tract infection, in that a concentration of less than 0.05ng/mL predicts the absence of a urinary tract infection and/or a concentration of more than 0.3ng/mL predicts the presence of a urinary tract infection.
In one embodiment, the method of the invention may comprise an additional step wherein the value of the concentration of procalcitonin in urine is compared to the value of the concentration of procalcitonin in plasma, since a ratio of the concentration of procalcitonin in urine to the concentration of procalcitonin in plasma of more than 1 predicts the presence of a urinary tract infection.
Subject of the present invention is also a kit for in vitro diagnosis and/or prediction of urinary tract infections, comprising aliquots of the reagents necessary for determining the concentration of procalcitonin in a urine sample and optionally a plasma sample.
Thus, for the first time, a rapid tool is provided that can be used to identify patients with urinary infections and/or to monitor the course of infection from the perspective of a particular treatment regimen.
In its simplest form, the kit contains one or more aliquots of a specific anti-calcitonin antibody and accompanying loose sheets containing, for example, instructions for interpretation of the diagnostic results, and optionally methods for collecting and storing urine and/or plasma samples. For the purposes of the present description, any antibody that can selectively bind to procalcitonin can be included in the kits claimed herein. In particular, the kit may contain one or more antibodies against procalcitonin, each developed against a different epitope of e.g. a protein, and possibly linked to a common antibody marker, e.g. a fluorophore or an enzyme. Where appropriate, the kit may include the use of monoclonal and/or polyclonal anti-procalcitonin antibodies on the market. The kit may also contain an accompanying leaflet. These leaflets may indicate the components of the kit and the recommended protocol. Further, the instructions may also contain information on the interpretation of the procalcitonin values obtained for the analyzed urine and plasma samples, and more specifically, as described above, a concentration of urinary procalcitonin of less than 0.05ng/mL predicts the absence of urinary tract infection, a concentration of greater than 0.3ng/mL predicts the presence of urinary tract infection, and a ratio of PCTur/PCTpl >1 predicts the presence of urinary tract infection, wherein PCTur is the patient's urinary procalcitonin and PCTpl is the plasma procalcitonin.
The kit may also contain one or more aliquots of a second antibody specific for the primary antibody. As known to those skilled in the art, and as mentioned above, the second antibody must be capable of specifically recognizing the constant part of the primary antibody used; the choice of the second antibody to be used will therefore depend on the animal immunized with the relevant epitope. The second antibody may be labeled with any of the compounds commonly used in antibody labeling.
The kit may also contain one or more aliquots of negative and/or positive controls. Negative control refers to any urine or plasma sample from a patient without urinary tract infection. In one embodiment, the negative control can be represented by a urine sample having a procalcitonin concentration of less than 0.05 ng/mL.
A positive control can be used to check the correctness of the procedure performed and the possible effectiveness of the method used, since it may contain plasma or urine samples of patients suffering from urinary tract infections. In particular, the most suitable positive control, but to which the invention is not limited, is a urine sample having a procalcitonin concentration of greater than 0.3 ng/mL.
The kit may also contain one or more aliquots of reagents for detecting procalcitonin in urine and/or plasma. These reagents consist of any solution that can be used to perform various steps that result in the identification of a value for the concentration of procalcitonin in the analysis sample. Specifically, a buffer solution such as, but not limited to, PBS (phosphate buffered saline); blocking solutions, for example PBS supplemented with bovine serum albumin.
The subject of the present invention is also the use of procalcitonin in the diagnosis, monitoring and severity assessment of urinary tract infections, such as infections associated with the use of urinary catheters.
Reported below are experimental results and examples for illustrating the reports contained in the present specification: the examples should not be considered as limiting the foregoing description and the claims.
Instructions for a population for use in a clinical study of patients suspected of having a urinary tract infection
Patients with suspected urinary tract infections who were resident in the ICU were enrolled in a clinical study. Each patient received the following tests simultaneously:
standard urinalysis (chemical and physical examination) and urine culture;
plasma PCT;
urine PCT.
Based on the urine culture results, 10 subjects positive to urine culture and 10 subjects negative to urine culture were received.
A total of 20 patients (9 females and 11 males) were received, with a mean age of 70 years. The age of the selected patients varied from 33 to 91 years.
Each patient must exhibit at least one of the following inclusion criteria:
-fever or hypothermia;
-leukocytosis/leukopenia;
-low back pain and/or dysuria;
-other unexplained signs of SIRS;
-FUO；
-recurrent UTI.
Exclusion criteria included:
1. oliguria/anuresis;
2. there is uretero sigmoidostomy;
3. renal dysfunction that impedes the acquisition of sufficient urine samples;
4. liver failure.
If it is notNot more than two species of microorganism having 105Development of CFU/mL (etiology of various microorganisms in 14-30% of cases) was considered positive for urine culture. In the case of Candida (Candida spp.), the significance threshold is considered to be 104CFU/mL. This is also true for gram-positive bacteria, in particular coagulase-negative enterococci and staphylococci, which in the case of antibacterial therapy tend to be considered to be less than 105The count of CFU/mL was significant.
Results of clinical study
The population positive for urine culture showed that urine PCT was higher than plasma PCT in 9 out of 10 cases (fig. 1).
Urine PCT averages 1.4ng/mL, while plasma PCT averages 0.4 ng/mL. Urine PCT ranged between 0.36 and 2.54ng/mL, while plasma PCT ranged between 0.06 and 1.22 ng/mL.
The median urine PCT value was 1.25ng/mL, while the median plasma PCT value was 0.24 ng/mL.
The ratio of urine to plasma PCT had values between 0.8 and 25.33ng/mL, with a mean of 7.32ng/mL and a median of 4.86 ng/mL.
The mean temperature of the subjects was 37.02 ℃, with 1 patient having a temperature <35 ℃, 3 patients having a temperature of > 36 ℃ and <37 ℃, 4 patients having a temperature of > 37 ℃ and <38 ℃, and > 2 patients having a temperature of 38 ℃.
White blood cell value (normal value 4.50 to 10.00X 10)3/. mu.L) in the range of 5.37 and 22.12X 103mu.L, wherein the average value is 12.22X 103μ L, median 11.55X 103/μL。
The percentage of neutrophils (normal 40.0 to 75.0%) ranged from 67.3 to 88.4%, with an average of 78.8%.
Creatinine (normal 0.50 to 0.90 mg/dL) in subjects ranged from a minimum of 0.3 to a maximum of 2.85mg/dL with a mean of 0.78 mg/dL.
To calculate the value of creatinine clearance, the following Cockcroft-Gault formula was used:
male [ (140-age) × body weight (kg)/(serum creatinine × 72) ]
Women [ (140-age) × body weight (kg) × 0.85/(serum creatinine × 72) ].
In the subjects, the clearance was in the range of 27 to 226.8 ml/min, with an average value of 129.16 ml/min and a median value of 115.4 ml/min.
The urine culture negative population showed that urine PCT was lower than plasma PCT in all patients.
Urine PCT averages 0.6ng/mL, while plasma PCT averages 4.44 ng/mL. Urine PCT ranged between 0.13 and 1.38ng/mL, while plasma PCT ranged between 0.35 and 25.72 ng/mL.
The median urine PCT value was 0.36ng/mL, while the median plasma PCT value was 1.36 ng/mL.
The ratio of urine and plasma PCT had values between 0.03 and 0.9ng/mL, with a mean of 0.40ng/mL and a median of 0.37 ng/mL.
The mean temperature of the subjects was 37.7 ℃, with 1 patient having a temperature of greater than or equal to 36 ℃ and less than 37 ℃, 1 patient having a temperature of greater than or equal to 37 ℃ and less than 38 ℃, and 8 patients having a temperature of greater than or equal to 38 ℃.
White blood cell values ranged from 4.27 and 39.2X 103mu.L, wherein the average value is 12.86X 103μ L, median 8.61X 103/μL。
The percentage of neutrophils ranged between 65.5 and 93.9%, with an average of 85.5%.
The creatinine of the subjects ranged from a minimum of 0.55 to a maximum of 1.61mg/dL with a mean of 0.97 mg/dL.
Creatinine clearance was in the range of 38.4 to 169.4 ml/min using the Cockcroft-Gault formula, with an average value of 78.72 ml/min and a median value of 76.1 ml/min.
In the population of urine culture negative patients, a PCTur value lower than the PCTpl value was observed in all 10 patients in the urine culture negative population, whereas in the population of urine culture positive, only 1 patient had a PCTur value lower than the PCTpl value (fig. 2). The latter was the only subject received with severe renal dysfunction and the patient exhibited creatinine clearance values estimated using the Cockcroft-Gault equation of 27 ml/min. Therefore, it is likely that in subjects with severe renal dysfunction, PCT accumulates in plasma without being properly excreted into urine, which results in PCTpl values greater than PCTur values despite culture-positivity.
In the population positive for urine culture, the median value for PCTur was 1.25ng/mL, whereas in the population negative for urine culture, the value was 0.36ng/mL, indicating a clear difference between the two groups.
The median value of PCTpl also showed significant differences: in the population positive for urine culture, this value (0.24 ng/mL) indicates that most subjects do not have any other infection; whereas in the urine culture negative population, this value (1.36 ng/mL) indicates that most patients had bacterial infections (figure 24).
To assess whether the accuracy of the PCT assay was affected by the use of urine as a sample matrix, 5 urine and serum samples of healthy individuals who could not detect PCT were each spiked into recombinant PCT and assayed in the KRYPTOR PCT assay. Recovery of PCT in urine was 20-30% lower than recovery of PCT in serum. Thus, the degree of reduction in urine recovery is relatively small, and the conclusions drawn above are valid even if the recovery in urine and serum are not the same. The urine PCT values measured in the clinical samples of the invention can be corrected by multiplying them by 1.25 to account for the reduced recovery in the urine matrix.
Statistical analysis
The data deduced from the clinical study results were subjected to statistical analysis to assess whether the PCTur/PCTpl ratio >1 could diagnose urinary tract infections with a certain sensitivity and specificity.
| Patients with infections | Patient without infection | Total up to | |
| Detection + | A | b | A+b |
| Detection + | C | d | C+d |
| Total up to | A+c | B+d |
| Patients with infections | Patient without infection | Total up to | |
| Detection + | 9 | 0 | 9 |
| Detection + | 1 | 10 | 11 |
| Total up to | 10 | 10 | 20 |
Sensitivity is the probability that an infected patient is positive for the test, in our example:
sensitivity = a/a + c =9/(9+1) =0.9, i.e. 90%.
Specificity, on the other hand, is the probability that a healthy subject is negative for the test, in our example:
specificity = d/b + d =10/(0+10) =1, i.e. 100%
We can also calculate a Positive Predictive Value (PPV), which corresponds to the proportion of subjects with infection and therefore correctly diagnosed as positive for detection of infection:
PPV =9/(9+0) =1 for a/a + b, i.e. 100%.
Example 1 determination of plasma Procalcitonin
Blood samples for analysis were collected from patients using BRAHMS PCT sensitive KRYPTOR, a kit designed for the dose of procalcitonin in automated immunofluorescence analysis of human serum or plasma samples (EDTA, heparin). The quantification method uses goat polyclonal antibodies against procalcitonin, europium cryptate and other substances such as buffers containing bovine serum albumin, immunoglobulin from naive mice, and potassium fluoride, to which a fluorescent marker is attached; an anti-calcitonin mouse monoclonal antibody also connected with a fluorescent marker XL665, and buffer solution, bovine serum albumin, mouse immunoglobulin and potassium fluoride; finally, a diluent of human serum, Kathon, EDTA is used for preparation.
The PCT assay in this assay is based on the TRACE technique (Time-Resolved amplified scrambled Emission) which measures the signal emitted from the immunocomplex delay. The sample is excited at 337nm with a nitrogen laser, the donor (cryptate) emits a long-lived fluorescence signal at 620nm in the millisecond range, while the acceptor (XL 665) produces a short-lived signal at 665nm in the nanosecond range. If immune complexes are formed, signal amplification and lifetime extension of the receptor signal occur simultaneously at 665nm and can be measured in microseconds.
The PCT molecule is sandwiched between the two antibodies and by measuring the length of the signal, PCT values are obtained, which are proportional to the emission time of the signal.
Example 2 determination of procalcitonin in urine
After clamping the outflow opening and sterilization, a urine sample is taken with a syringe from the appropriate drainage position of the urine catheter. Approximately 4mL of urine was transferred to a suitable tube and transported to an analytical laboratory. Once the sample is removed, the assay for urinary PCT is performed according to the protocol provided for plasma PCT as described in example 1.
Reference to the literature
Hooton TM et al, 2009International clinical practice guidelines of the American society for infectious diseases: diagnosis, prevention, and treatment of urinary tract infections in adults associated with urinary catheters (diagnostic, prevention, and treatment of catheter-assisted urinary tract infections: 2009International Clinical practices from the group of infectious diseases Society of America.) clinin urinary Mar 1;50(5): 625-63.
Claims (16)
1. Use of a substance for the detection of procalcitonin for the preparation of a reagent for the diagnosis and/or monitoring of urinary tract infections by an in vitro method comprising the step of determining the concentration of procalcitonin in a urine sample from a patient.
2. The use of claim 1, wherein said method further comprises the step of determining the concentration of procalcitonin in the plasma of said patient.
3. Use according to claim 1 or 2, wherein the method determines the concentration of procalcitonin by means of a primary antibody specific for procalcitonin.
4. Use according to claim 3, wherein the primary antibody is directly labelled with a fluorescent dye selected from the group consisting of: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL 665.
5. The use of claim 3, wherein the method determines the procalcitonin concentration by labeling the second antibody with a compound selected from the group consisting of: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL 665.
6. The use of claim 5, wherein the second antibody is specific for the primary antibody.
7. The use according to any one of claims 1 to 6, wherein the urinary tract infection is associated with the use of urinary catheters.
8. The use according to any one of claims 1 to 7, wherein the method further comprises the step of comparing the concentration of procalcitonin in urine with one or more values, whereby a concentration below 0.05ng/ml predicts the absence of urinary tract infection and/or a concentration above 0.3ng/ml predicts the presence of urinary tract infection.
9. The use according to any one of claims 2-8, wherein said method further comprises the step of comparing the value of said procalcitonin concentration in urine with the value of said procalcitonin concentration in plasma, whereby a ratio between said procalcitonin concentration in urine and said procalcitonin concentration in plasma of more than 1 predicts the presence of a urinary tract infection.
10. Use of a substance for the detection of procalcitonin for the preparation of a kit for the in vitro diagnosis and/or monitoring of urinary tract infections using a urine sample, said kit comprising aliquots of the reagents required for determining the concentration of procalcitonin in the urine sample.
11. Use according to claim 10, said kit comprising one or more aliquots of primary antibodies specific for procalcitonin.
12. The use of claim 11, wherein the primary antibody is an antibody directly labeled with a compound selected from the group consisting of: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL 665.
13. The use of claim 12, said kit further comprising one or more aliquots of a second antibody labeled with a compound selected from the group consisting of: hydroxycoumarin, aminocoumarin, methoxycoumarin, europium, samarium, FITC, Cy3, Cy5, Cy2, Cy7, XL 665.
14. The use of any one of claims 10 to 13, wherein the reagent comprises one or more aliquots of buffer solution and/or one or more aliquots of binding solution and/or one or more aliquots of reagent for detecting the labeled antibody.
15. Use according to any one of claims 10 to 14, the kit further comprising one or more aliquots of a negative control and/or one or more aliquots of a positive control.
16. Use according to claim 15, wherein the negative control is a urine sample with a procalcitonin concentration below 0.05ng/ml and the positive control is a urine sample with a procalcitonin concentration above 0.3 ng/ml.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM2010A000121 | 2010-03-18 | ||
| IT000121A ITRM20100121A1 (en) | 2010-03-18 | 2010-03-18 | MOLECULAR MARKERS FOR URINARY PATH INFECTIONS. |
| PCT/IB2011/051073 WO2011114287A2 (en) | 2010-03-18 | 2011-03-15 | Molecular markers for urinary tract infections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1180392A1 HK1180392A1 (en) | 2013-10-18 |
| HK1180392B true HK1180392B (en) | 2015-12-24 |
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