Acute InfectionNCT06040684
Development of Antibodies Against Transplant Kidney After Infection
An observational study of Acute Infection and Kidney Failure, run by University Hospital Ostrava at 1 site in Czechia.
Trial summary
Kidney transplantation is the best method of renal replacement in patients with irreversible renal failure. One of the biggest problems today is premature loss of function of the transplanted kidney. This occurs most often on the basis of chronic humoral rejection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Infection, Kidney Failure
- What is being tested?
- Level of antibodies
- How many people
- 30 participants
- Where
- 1 siteCzechia
- Study dates
- 1 Aug 2018to 31 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Kidney transplant recipients with acute infection (viral, bacterial or fungal) requiring acute inpatient care
Who may be able to join
- Age 18 years and over.
- A kidney transplant patient - from a living donor or from a cadaveric donor (donor after circulatory or brain death). The patient will be included after 1st transplant and possible retransplantation.
- The patient is hospitalized or newly admitted to the FN Ostrava internal clinic for acute infection + requires the reduction of immunosuppressive therapy (dose reduction or discontinuation of any of the maintenance immunosuppressive preparations - tacrolimus, cyclosporin A, sirolimus, everolimus, azathioprine, mycophenolate).
- Acute infection (to be admitted to an internal clinic - determine the time of admission or the time of the first symptom of infection in the already hospitalized) occurred at least more than 48 hours after transplantation (from reperfusion time) and a maximum of 10 years after transplantation.
- The patient did not receive intravenous immunoglobulins within the last 24 hours prior to first sampling.
- This is not a pregnant woman.
Who cannot join
- Patient's death before the 2nd blood sampling.
- The patient condition was conclusively determined as something other than acute infection (acute rejection episode, acute pancreatitis, malignant tumor, ...). Unfamiliarity with localization of the infection or its origin, assuming an infectious etiology, is NOT an exclusion criterion.
- The patient was graftectomized - removal of the transplanted kidney, between the 1st and 2nd antibody determination.
- Detection of pregnancy when the term of conception is calculated before the 2nd antibody count.
- One or more transfusions of the erythrocytes or plasma between the 1st and 2nd measurements were administered to the patient.
Trial locations and contacts
1 site in 1 country.
Czechia1 site
University Hospital Ostrava
Ostrava, Moravian-Silesian Region, 708 52
About this study
Kidney transplantation is the best method of renal replacement in patients with irreversible renal failure. One of the biggest problems today is premature loss of function of the transplanted kidney. This occurs most often on the basis of chronic humoral rejection. This is the immune response to the kidney, in which the specific antibodies play a crucial role (both against the HLA and the non-HLA system).
The aim of this study is to analyze one of the situations where the production of antibodies can begin to occur. This is a serious acute infection (bacterial, viral, or fungal), where it is necessary to significantly reduce doses of immunosuppressives. At the time of reduced immunosuppression, the immune system can recognize the transplanted kidney as foreign to the human body and begin to fight against it.
In this study, the investigators will monitor antibodies against the transplanted kidney in patients with severe acute infection. A serious infection in this study is one that requires acute hospitalization and reduced doses of immunosuppressive drugs. The researchers will measure the antibodies in the blood upon admission and then in 5 weeks.
Read the detailed description
Kidney transplantation significantly improves the prognosis and quality of life of patients with irreversible renal failure (end-stage kidney disease), requiring hemodialysis or peritoneal dialysis. The length of the function of the transplanted kidney depends on a number of factors. One of the most significant deterioration factors and subsequent graft function failure, in the long run, is the production of antibodies against HLA as well as transplant antigens that lead to acute or chronic humoral rejection. Chronic humoral rejection leading to transplant glomerulopathy is the most common cause of loss of function of the transplanted kidney. Treatment interventions in this area are still ineffective.
In spite of immunosuppressive therapy, some patients develop anti-transplant antibodies (both against HLA and non-HLA antibody molecules) even with stable graft function. However, these patients have an increased risk of losing their function due to chronic humoral rejection. The HLA-DR and HLA-DQ molecules have the greatest immunogenicity.
Patients after kidney transplantation may have many complications. Both surgical (vascular anastomoses stenoses, wound healing problems, graft vascular thromboses, lymphocele, urinary leakage) and non-surgical, some of which are immune-compromised (rejection) and others, result from the mechanism of action of immunosuppressive preparations (infections, cardiovascular effects). Amongst potentially life-threatening conditions include acute infections. Immunosuppressed infections have their own specifics. In addition to the increased risk of infections; also a different spectrum of possible originators is known. It is also possible to encounter opportunistic infections - pneumocystis, cytomegalovirus, polyomavirus infections. Another specific feature is often a different course of infection - patients may not have significantly expressed clinical or laboratory findings and may progress rapidly. For these reasons, physicians are often forced to significantly reduce immunosuppression rates in patients with acute infection, despite the increased risk of developing rejection. This situation increases the risk of initiation by both cell-mediated rejection and antibody-mediated rejection. Signs of rejection are very nonspecific and the only diagnostic method is graft biopsy. Previous studies have shown that the production of antibodies to the transplanted kidney is preceded by clinical signs of deterioration in graft function over weeks to months. Patients included in the study according to the criteria will be examined for the presence of HLA antibodies and non-HLA on admission (within 48 hours of admission) and 5 weeks after the first sample method LUMINEX xMAP.
- Conditions
- Acute Infection, Kidney Failure
- Being tested
- Level of antibodies
- Keywords
- kidney transplant, HLA antibodies, acute infection
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Level of antibodiesDiagnostic test
The level of antibodies against transplanted kidney in patients with a severe acute infection will be measured upon admission and then in 5 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Level of antibodies in kidney transplant recipients | Patients with kidney transplant with a severe acute infection will be enrolled in the study. Levels of antibodies in these patients will be analyzed. Receives: Diagnostic Test: Level of antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Production of HLA and nonHLA antibodies - Luminex
Screening for HLA and nonHLA antibodies by Luminex. The test result will be positive (MFI - mean fluorescence intensity above 300) or negative.
Measured: 42 months
Secondary outcomes (13)
Analysis of antibody formation according to age
The formation of antibodies will be analysed according to the age of the patients in years.
Measured: 42 months
Analysis of antibody formation according to time from transplantation
The formation of antibodies will be analysed according to the time from transplantation in months.
Measured: 42 months
Creatinine value
The baseline kidney function will be assessed (according to the KDIGO organization) The kidney will be classified as a normal function, 1st, 2nd, 3rd according to the creatinine value).
Measured: 42 months
Input Inflammatory Parameters - CRP (C-reactive protein)
The input inflammatory parameters will be assessed (CRP (mg/l).
Measured: 42 months
Input Inflammatory Parameters - IL-6 (Interleukin-6)
The input inflammatory parameters will be assessed (IL-6 (ng/l).
Measured: 42 months
Number of HLA mismatches during transplant (0-6)
The number of HLA mismatches during transplant (0-6) will be recorded.
Measured: 42 months
Length of immunosuppression reduction
The length of immunosuppression reduction will be analysed in 3 categories - up to 5 days, 5-10 days and over 10 days.
Measured: 42 months
Delayed graft function after transplantation
The delayed graft function after transplantation will be assessed in 2 categories - YES / NO -as a need for haemodialysis in the first week after transplantation.
Measured: 42 months
Long-term graft function
The long-term graft function will be assessed by the last early graft function (eGF) in ml / sec- 3 categories - normal function, G1-2 and G3-5 by KDIGO.
Measured: 42 months
Type of infection
The type of infection observed in the patients will be assessed and recorded - urinary, respiratory, other - determined by the doctor when the patient is discharged.
Measured: 42 months
Presence of antibodies
The presence of antibodies (YES/NO) will be determined in patients using the LUMINEX method - antibody value using MFI - mean fluorescence intensity.
Measured: 42 months
EGF value
The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the EGF value (ml/sec)
Measured: 42 months
Proteinuria
The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the proteinuria (g/l)
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2023
- Study start1 Aug 2018
- Primary completion30 Nov 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Ostrava
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zdeněk Lys, MD, Principal investigator, University Hospital Ostrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06040684
- Sponsor's protocol ID
- INT-01-HLATX-Kidney
- Other IDs
- 15/RVO-FNOs/2018
- Status last verified
- Sep 2023
- First submitted
- 23 May 2018
- Last updated
- 15 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators do not plan to make individual participant data available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Antibodies Against Transplant Kidney After Infection
- ClinicalTrials.gov ID
- NCT06040684
- Acronym / sponsor ID
- INT-01-HLATX-Kidney
- Conditions
- Acute Infection, Kidney Failure
- Keywords
- kidney transplant, HLA antibodies, acute infection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital OstravaUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 15 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Kidney transplantation is the best method of renal replacement in patients with irreversible renal failure. One of the biggest problems today is premature loss of function of the transplanted kidney. This occurs most often on the basis of chronic humoral rejection. This is the immune response to the kidney, in which the specific antibodies play a crucial role (both against the HLA and the non-HLA system).
The aim of this study is to analyze one of the situations where the production of antibodies can begin to occur. This is a serious acute infection (bacterial, viral, or fungal), where it is necessary to significantly reduce doses of immunosuppressives. At the time of reduced immunosuppression, the immune system can recognize the transplanted kidney as foreign to the human body and begin to fight against it.
In this study, the investigators will monitor antibodies against the transplanted kidney in patients with severe acute infection. A serious infection in this study is one that requires acute hospitalization and reduced doses of immunosuppressive drugs. The researchers will measure the antibodies in the blood upon admission and then in 5 weeks.
Detailed description
Kidney transplantation significantly improves the prognosis and quality of life of patients with irreversible renal failure (end-stage kidney disease), requiring hemodialysis or peritoneal dialysis. The length of the function of the transplanted kidney depends on a number of factors. One of the most significant deterioration factors and subsequent graft function failure, in the long run, is the production of antibodies against HLA as well as transplant antigens that lead to acute or chronic humoral rejection. Chronic humoral rejection leading to transplant glomerulopathy is the most common cause of loss of function of the transplanted kidney. Treatment interventions in this area are still ineffective.
In spite of immunosuppressive therapy, some patients develop anti-transplant antibodies (both against HLA and non-HLA antibody molecules) even with stable graft function. However, these patients have an increased risk of losing their function due to chronic humoral rejection. The HLA-DR and HLA-DQ molecules have the greatest immunogenicity.
Patients after kidney transplantation may have many complications. Both surgical (vascular anastomoses stenoses, wound healing problems, graft vascular thromboses, lymphocele, urinary leakage) and non-surgical, some of which are immune-compromised (rejection) and others, result from the mechanism of action of immunosuppressive preparations (infections, cardiovascular effects). Amongst potentially life-threatening conditions include acute infections. Immunosuppressed infections have their own specifics. In addition to the increased risk of infections; also a different spectrum of possible originators is known. It is also possible to encounter opportunistic infections - pneumocystis, cytomegalovirus, polyomavirus infections. Another specific feature is often a different course of infection - patients may not have significantly expressed clinical or laboratory findings and may progress rapidly. For these reasons, physicians are often forced to significantly reduce immunosuppression rates in patients with acute infection, despite the increased risk of developing rejection. This situation increases the risk of initiation by both cell-mediated rejection and antibody-mediated rejection. Signs of rejection are very nonspecific and the only diagnostic method is graft biopsy. Previous studies have shown that the production of antibodies to the transplanted kidney is preceded by clinical signs of deterioration in graft function over weeks to months. Patients included in the study according to the criteria will be examined for the presence of HLA antibodies and non-HLA on admission (within 48 hours of admission) and 5 weeks after the first sample method LUMINEX xMAP.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Level of antibodies in kidney transplant recipients | – | Diagnostic Test: Level of antibodiesPatients with kidney transplant with a severe acute infection will be enrolled in the study. Levels of antibodies in these patients will be analyzed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Kidney transplant recipients with acute infection (viral, bacterial or fungal) requiring acute inpatient care
Key inclusion criteria (6 listed)
- Age 18 years and over.
- A kidney transplant patient - from a living donor or from a cadaveric donor (donor after circulatory or brain death). The patient will be included after 1st transplant and possible retransplantation.
- The patient is hospitalized or newly admitted to the FN Ostrava internal clinic for acute infection + requires the reduction of immunosuppressive therapy (dose reduction or discontinuation of any of the maintenance immunosuppressive preparations - tacrolimus, cyclosporin A, sirolimus, everolimus, azathioprine, mycophenolate).
- Acute infection (to be admitted to an internal clinic - determine the time of admission or the time of the first symptom of infection in the already hospitalized) occurred at least more than 48 hours after transplantation (from reperfusion time) and a maximum of 10 years after transplantation.
- The patient did not receive intravenous immunoglobulins within the last 24 hours prior to first sampling.
Key exclusion criteria (5 listed)
- Patient's death before the 2nd blood sampling.
- The patient condition was conclusively determined as something other than acute infection (acute rejection episode, acute pancreatitis, malignant tumor, ...). Unfamiliarity with localization of the infection or its origin, assuming an infectious etiology, is NOT an exclusion criterion.
- The patient was graftectomized - removal of the transplanted kidney, between the 1st and 2nd antibody determination.
- Detection of pregnancy when the term of conception is calculated before the 2nd antibody count.
- One or more transfusions of the erythrocytes or plasma between the 1st and 2nd measurements were administered to the patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Level of antibodiesThe level of antibodies against transplanted kidney in patients with a severe acute infection will be measured upon admission and then in 5 weeks. | Diagnostic test | Level of antibodies in kidney transplant recipients |
Primary outcome
Production of HLA and nonHLA antibodies - Luminex
Time frame: 42 months
Screening for HLA and nonHLA antibodies by Luminex. The test result will be positive (MFI - mean fluorescence intensity above 300) or negative.
13 secondary outcomes
Analysis of antibody formation according to age
Time frame: 42 months
Analysis of antibody formation according to time from transplantation
Time frame: 42 months
Creatinine value
Time frame: 42 months
Input Inflammatory Parameters - CRP (C-reactive protein)
Time frame: 42 months
Input Inflammatory Parameters - IL-6 (Interleukin-6)
Time frame: 42 months
Number of HLA mismatches during transplant (0-6)
Time frame: 42 months
Length of immunosuppression reduction
Time frame: 42 months
Delayed graft function after transplantation
Time frame: 42 months
Long-term graft function
Time frame: 42 months
Type of infection
Time frame: 42 months
Presence of antibodies
Time frame: 42 months
EGF value
Time frame: 42 months
Proteinuria
Time frame: 42 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Individual participant dataSharing planned: No. The investigators do not plan to make individual participant data available to other researchers.
Related trials for Acute Infection
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruiting
Expanded Diagnostic Strategy in Older Adults Hospitalized With Community-Acquired Acute Respiratory Infection
Acute Respiratory Infection
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zdeněk Lys, MD principal investigator
University Hospital Ostrava
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Infection and Kidney Failure, run by University Hospital Ostrava at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Production of HLA and nonHLA antibodies - Luminex (time frame: 42 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2023.