Kidney Graft DysfunctionKALIMBONCT03155763
Histology of Implantation Biopsies and Kidney Allograft Outcomes
An observational study of Kidney Graft Dysfunction, run by Andriy Trailin at 1 site in Ukraine.
Trial summary
The morphology of transplanted kidney is considered to be important for graft outcomes in early and late posttransplant period. Individual histological lesions at the time of kidney transplantation, such as sclerosis of glomeruli, vascular narrowing and interstitial fibrosis, and composite histological lesions, which… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Graft Dysfunction
- What is being tested?
- Intraoperative kidney allograft preimplantation biopsy; Intraoperative kidney allograft postreperfusion biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 130 participants
- Where
- 1 siteUkraine
- Study dates
- 1 Apr 2005to 31 Dec 2015
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All recipients and donors were Caucasians and Ukrainians.
Who may be able to join
- adult kidney transplant recipients who underwent transplantation at Zaporizhzhia Transplant Center;
- cadaveric or living single kidney only transplant;
- informed written consent;
- adequate intraoperative biopsy (in total ≥ 7 glomeruli and ≥ 1 arteries in preimplant and postreperfusion biopsies);
- complete follow-up data up to 5 years.
Who cannot join
- not consent with research;
- non-complete follow-up data up to 5 years.
Trial locations and contacts
1 site in 1 country.
Ukraine1 site
Laboratory Diagnostics and General Pathology Department, State Institution "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine"
Zaporizhzhya, 69096
About this study
Official title: Impact of Acute and Chronic Individual Histological Lesions and Composite Scores in Implantation Biopsies on Short-term and Long-term Kidney Allograft Outcomes
The morphology of transplanted kidney is considered to be important for graft outcomes in early and late posttransplant period. Individual histological lesions at the time of kidney transplantation, such as sclerosis of glomeruli, vascular narrowing and interstitial fibrosis, and composite histological lesions, which integrate histopathological findings in different compartments, showed association with suboptimal graft outcomes. However there are no consistent association between individual or composite lesions and transplant outcomes. Some possible explanations for such inconsistent results are non-uniformity in grading histological lesions or in defining graft outcomes. Furthermore, studies vary in terms of patient selection, and some results are not corrected for covariates. It is also unclear, whether acute biopsy features associated with the donor kidney can provide prognostic information, in addition to the chronic lesions? This single-center study aimed to evaluate which acute and chronic histological lesions and composite histological scores in donor kidney intraoperative biopsies alone or in combination with clinical variables are best associated with short- and long-term kidney graft outcomes, such as impairment of early kidney allograft function, immunological acute kidney allograft rejection, pyelonephritis, allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years, and graft survival at 1 and 5 years.
Read the detailed description
130 consecutive patients with end-stage renal disease (ESRD), receiving a kidney only transplant from April 2005 to December 2010 in a single center, and having both intraoperative biopsies with ≥ 7 glomeruli and ≥ 1 arteries and complete follow-up data up to 5 years were included in the study.
Intraoperative biopsy consisted of preimplant biopsy (at the backtable, 1 core) and 30-minutes postreperfusion biopsy (1 core), which were taken in order to study the impact of ischemia/reperfusion injury on transplant outcomes and to serve a reference for subsequent biopsies.
Donor population included live donors (32.6%), ideal deceased donors (50%), expanded-criteria donors (7.9%) and 9.0% of non-heart-beating donors. Donors were subjected to donor evaluation protocol in accordance with local guidelines, including a standard clinical, instrumental and laboratory examination.
All recipients and donors were Caucasians.
Histological scoring Needle (14-18-gauge) biopsies were obtained and tissue was fixed in 10% buffered formalin and embedded in paraffin. A 3-4 µm sections of preimplant and postreperfusion kidney allograft implantation biopsies (KALIMBO) were stained for light microscopy with hematoxylin-eosin (3 slides), periodic acid-Schiff (3 slides), and Masson's trichrome (1 slide). A minimum of 21 tissue sections were examined for each biopsy. Banff-1997 criteria for posttransplant biopsies, Banff-2016 criteria for preimplant biopsies, as well as criteria suggested by Remuzzi et al. (1999) and Cosyns et al. (1998) were applied for scoring.
Based on the estimation of individual acute and chronic lesions, the acute, chronic and total posttransplant and preimplant Banff scores, Remuzzi score, and acute, chronic and total lesion indexes by Cosyns were calculated. In addition, previously published composite histological scores, such as chronic allograft damage index (CADI), donor damage score (DDS), chronic damage score (CDS), and interstitial fibrosis and fibrous thickening score (CIV) were computed.
Clinical risk factors and outcomes examined The analysis was performed 60 months later after the last transplant in the study population. Donor, graft and recipient characteristics and transplant outcomes were extracted from archival patient records and outpatient cards blinded to all pathologic data. Data were retrieved on donor source, sex and age, and cause of death, donation after cardiac death or expanded criteria donation for deceased donors.
Recipient's pretransplant variables included: age, gender, cause of ESRD, body mass index (BMI), dialysis modality and duration, previous transplants, and presence of chronic arterial hypertension, defined as a regular intake of antihypertensive drugs. The information related to transplantation (cold ischemia time and second warm ischemia time) was also obtained. Posttransplant data retrieved were limited to initial graft function (immediate, delayed or slow), and the number and time of occurrence of acute rejection episodes or pyelonephritis, and time of graft failure defined as return to dialysis therapy.
All recipients received triple maintenance immunosuppressive therapy consisting of calcineurin-inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroid. Each patient, enrolled in this study, was followed for five years until death/return to dialysis or until December 2015.
The end points of the study were impairment of early kidney allograft function, immunological acute kidney allograft rejection, pyelonephritis, allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years, and graft survival at 1 and 5 years.
- Conditions
- Kidney Graft Dysfunction
- Being tested
- Intraoperative kidney allograft preimplantation biopsy; Intraoperative kidney allograft postreperfusion biopsy
- Keywords
- kidney transplantation, implantation biopsy, histology, allograft function, allograft survival
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraoperative kidney allograft preimplantation biopsy; Intraoperative kidney allograft postreperfusion biopsyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Five-year death-censored kidney allograft survival
The time of graft failure was defined as return to dialysis therapy
Measured: Five years
Secondary outcomes (6)
Delayed graft function
Delayed graft function was defined as the need for dialysis in the first postoperative week without evidence of acute rejection or pyelonephritis
Measured: The day 8
Slow graft function
Slow graft function was defined as serum creatinine on day seven ≥300 μmol/L without evidence of acute rejection or pyelonephritis.
Measured: The day 8
Acute rejection
Acute rejection was defined by characteristic clinical symptoms and ultrasound findings and by the need for treatment, with or without biopsy confirmation.
Measured: During five years
Pyelonephritis
Pyelonephritis was defined by characteristic symptoms, a urine sediment analysis, and a urinary culture test.
Measured: During five years
Allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years
Allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years was assessed with glomerular filtration rate (CKD-EP equation).
Measured: During five years
One-year death-censored kidney allograft survival
The time of graft failure was defined as return to dialysis therapy
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start1 Apr 2005
- Primary completion31 Dec 2015
- Study completion31 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Graft DysfunctionStudies 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andriy Trailin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andriy Trailin, State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine
- Investigators
- Andriy V Trailin, MD, DSc, Principal investigator, State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03155763
- Sponsor's protocol ID
- 0105U007599
- Acronym
- KALIMBO
- Status last verified
- May 2017
- First submitted
- 13 May 2017
- Last updated
- 18 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We are going to share raw data on kidney baseline histology, graft function and survival up to 5 years after the publication of all results obtained. IPD will be available through an open access repository of data (ClinicalTrials.gov)
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Acute and Chronic Individual Histological Lesions and Composite Scores in Implantation Biopsies on Short-term and Long-term Kidney Allograft Outcomes
- ClinicalTrials.gov ID
- NCT03155763
- Acronym / sponsor ID
- KALIMBO / 0105U007599
- Conditions
- Kidney Graft Dysfunction
- Keywords
- kidney transplantation, implantation biopsy, histology, allograft function, allograft survival
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Andriy TrailinUniversity, hospital or other
- Study start
- 1 Apr 2005 (actual)
- Primary completion
- 31 Dec 2015 (actual)
- Study completion
- 31 Dec 2015 (actual)
- First posted
- 16 May 2017 (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.
The morphology of transplanted kidney is considered to be important for graft outcomes in early and late posttransplant period. Individual histological lesions at the time of kidney transplantation, such as sclerosis of glomeruli, vascular narrowing and interstitial fibrosis, and composite histological lesions, which integrate histopathological findings in different compartments, showed association with suboptimal graft outcomes. However there are no consistent association between individual or composite lesions and transplant outcomes. Some possible explanations for such inconsistent results are non-uniformity in grading histological lesions or in defining graft outcomes. Furthermore, studies vary in terms of patient selection, and some results are not corrected for covariates. It is also unclear, whether acute biopsy features associated with the donor kidney can provide prognostic information, in addition to the chronic lesions? This single-center study aimed to evaluate which acute and chronic histological lesions and composite histological scores in donor kidney intraoperative biopsies alone or in combination with clinical variables are best associated with short- and long-term kidney graft outcomes, such as impairment of early kidney allograft function, immunological acute kidney allograft rejection, pyelonephritis, allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years, and graft survival at 1 and 5 years.
Detailed description
130 consecutive patients with end-stage renal disease (ESRD), receiving a kidney only transplant from April 2005 to December 2010 in a single center, and having both intraoperative biopsies with ≥ 7 glomeruli and ≥ 1 arteries and complete follow-up data up to 5 years were included in the study.
Intraoperative biopsy consisted of preimplant biopsy (at the backtable, 1 core) and 30-minutes postreperfusion biopsy (1 core), which were taken in order to study the impact of ischemia/reperfusion injury on transplant outcomes and to serve a reference for subsequent biopsies.
Donor population included live donors (32.6%), ideal deceased donors (50%), expanded-criteria donors (7.9%) and 9.0% of non-heart-beating donors. Donors were subjected to donor evaluation protocol in accordance with local guidelines, including a standard clinical, instrumental and laboratory examination.
All recipients and donors were Caucasians.
Histological scoring Needle (14-18-gauge) biopsies were obtained and tissue was fixed in 10% buffered formalin and embedded in paraffin. A 3-4 µm sections of preimplant and postreperfusion kidney allograft implantation biopsies (KALIMBO) were stained for light microscopy with hematoxylin-eosin (3 slides), periodic acid-Schiff (3 slides), and Masson's trichrome (1 slide). A minimum of 21 tissue sections were examined for each biopsy. Banff-1997 criteria for posttransplant biopsies, Banff-2016 criteria for preimplant biopsies, as well as criteria suggested by Remuzzi et al. (1999) and Cosyns et al. (1998) were applied for scoring.
Based on the estimation of individual acute and chronic lesions, the acute, chronic and total posttransplant and preimplant Banff scores, Remuzzi score, and acute, chronic and total lesion indexes by Cosyns were calculated. In addition, previously published composite histological scores, such as chronic allograft damage index (CADI), donor damage score (DDS), chronic damage score (CDS), and interstitial fibrosis and fibrous thickening score (CIV) were computed.
Clinical risk factors and outcomes examined The analysis was performed 60 months later after the last transplant in the study population. Donor, graft and recipient characteristics and transplant outcomes were extracted from archival patient records and outpatient cards blinded to all pathologic data. Data were retrieved on donor source, sex and age, and cause of death, donation after cardiac death or expanded criteria donation for deceased donors.
Recipient's pretransplant variables included: age, gender, cause of ESRD, body mass index (BMI), dialysis modality and duration, previous transplants, and presence of chronic arterial hypertension, defined as a regular intake of antihypertensive drugs. The information related to transplantation (cold ischemia time and second warm ischemia time) was also obtained. Posttransplant data retrieved were limited to initial graft function (immediate, delayed or slow), and the number and time of occurrence of acute rejection episodes or pyelonephritis, and time of graft failure defined as return to dialysis therapy.
All recipients received triple maintenance immunosuppressive therapy consisting of calcineurin-inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroid. Each patient, enrolled in this study, was followed for five years until death/return to dialysis or until December 2015.
The end points of the study were impairment of early kidney allograft function, immunological acute kidney allograft rejection, pyelonephritis, allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years, and graft survival at 1 and 5 years.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All recipients and donors were Caucasians and Ukrainians.
Key inclusion criteria (5 listed)
- adult kidney transplant recipients who underwent transplantation at Zaporizhzhia Transplant Center;
- cadaveric or living single kidney only transplant;
- informed written consent;
- adequate intraoperative biopsy (in total ≥ 7 glomeruli and ≥ 1 arteries in preimplant and postreperfusion biopsies);
- complete follow-up data up to 5 years.
Key exclusion criteria (2 listed)
- not consent with research;
- non-complete follow-up data up to 5 years.
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 |
|---|---|---|
| Intraoperative kidney allograft preimplantation biopsy; Intraoperative kidney allograft postreperfusion biopsy | Procedure or surgery | – |
Primary outcome
Five-year death-censored kidney allograft survival
Time frame: Five years
The time of graft failure was defined as return to dialysis therapy
6 secondary outcomes
Delayed graft function
Time frame: The day 8
Slow graft function
Time frame: The day 8
Acute rejection
Time frame: During five years
Pyelonephritis
Time frame: During five years
Allograft function at 1, 3, 6, 12 months, 2, 3, 4 and 5 years
Time frame: During five years
One-year death-censored kidney allograft survival
Time frame: One year
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 18 May 2017.
- Individual participant dataSharing planned: Yes. We are going to share raw data on kidney baseline histology, graft function and survival up to 5 years after the publication of all results obtained. IPD will be available through an open access repository of data (ClinicalTrials.gov)
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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.
Andriy V Trailin, MD, DSc principal investigator
State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine
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 Kidney Graft Dysfunction, run by Andriy Trailin at 1 site in Ukraine.
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 5 inclusion and 2 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 18 May 2017. 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 Ukraine. 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?
Five-year death-censored kidney allograft survival (time frame: Five years). 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 18 May 2017.