Kidney TransplantationNCT02346968
Evaluation of CAF22 After Renal Transplantation
An observational study of Kidney Transplantation and Delayed Graft Function, run by Insel Gruppe AG, University Hospital Bern at 2 sites in 2 countries.
Trial summary
Established markers of kidney function, such as creatinine, have considerable limitations in the diagnosis of delayed graft function (DGF) after kidney transplantation (KT). Indeed, creatinine does not accurately reflect minor changes of renal function as its levels change only upon significant fluctuations of the… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney Transplantation, Delayed Graft Function
- What is being tested?
- Blood and urine sampling
- How many people
- 99 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 8 Oct 2014to 27 Sep 2018
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with end stage renal disease (ESRD) planned to undergo kindey transplantation in Bern University Hospital will be screened consecutively, informed and asked for written inform consent.
Who may be able to join
- Age ≥ 18 years old
- Written informed consent
- All patients planned to undergo kidney transplantation
Who cannot join
- Age <18 years old
- Pregnancy
- Other individuals especially in need of protection (according to the Swiss Academy of Medical Sciences)
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Germany1 site
Department of Nephrology, University Hospital of Essen
Essen, 45147
Switzerland1 site
Dep. of Nephrology, Bern University Hospital
Bern, 3010 Bern
About this study
Official title: Evaluation of Serum and Urinary C-terminal Agrin Fragment-22 (CAF22) as Novel Renal Function Marker in Kidney Transplant Recipients - A Prospective Observational Study
Established markers of kidney function, such as creatinine, have considerable limitations in the diagnosis of delayed graft function (DGF) after kidney transplantation (KT). Indeed, creatinine does not accurately reflect minor changes of renal function as its levels change only upon significant fluctuations of the latter. CAF22 is a molecule which arises from the degradation of a larger protein and it is proposed to be a reliable and more sensitive marker of renal function. This study aims to further clarify this issue by measuring blood and urine concentrations of CAF22 and comparing them with creatinine levels before and after KT.
The main assumption is that blood CAF22 levels could serve as a more sensitive kidney function biomarker than creatinine post-KT to detect DGF.
Read the detailed description
Background
Kidney transplantation (KT) is the most appropriate therapy of end stage renal disease (ESRD). While the number of kidney donors remained stable during the last decade the number of patients waiting for a kidney transplantation are rapidly increasing resulting in utilization of an increasing numbers of marginal renal transplants. These kidneys show a relatively high percentage of delayed graft function (DGF), which complicates post-transplant management and increases both the duration of initial hospitalization and the cost of transplantation.
Exact measurement of glomerular filtration rate (GFR) is complex in the clinical setting and thus GFR is usually estimated from serum creatinine levels through creatinine-based equations such as the MDRD or the CKD-EPI equations. Particularly, this is the case in kidney recipients with DGF, in whom creatinine levels remain high and they have to undergo dialysis. Creatinine is dialyzable, so that it cannot reflect the actual renal function in this setting due to fluctuations of its levels. Thus there is emergent need for a more accurate renal biomarker.
CAF22 is the C-terminal 22 kDa domain of agrin. Agrin is cleaved by its specific protease neurotrypsin at two distinct sites, whereas cleavage at the beta site generates a 22 kDa C-terminal fragment (CAF22). In the kidney agrin is part of the basal lamina, where it is the major contributor of the anionic potential of the glomerular basement membrane (GBM). There are indices for a proteolytic activity selectively shedding the C-terminal part of agrin of the GBM. Recently, a 19-fold increase of CAF22 levels in ESDR was observed, which was reduced in patients receiving KT, qualifying CAF22 as effective renal function marker. Additionally, current data support that CAF22 levels are not influenced by inflammatory processes, steroids or by hemodialysis with a standard dialysis membrane.
Objective
Primary:
- to compare CAF22 versus creatinine as biomarkers for DGF prediction in patients undergoing kidney transplantation
Secondary:
- to evaluate the kinetics of CAF levels related with the graft function outcomes "immediate graft function (IGF)" and "delayed graft function (DGF)"
- to elucidate whether CAF can make estimations on the required hemodialysis days of patients with delayed graft function
Methods
Research project with humans associated with the collection of biologic material and health-related data. Prospective, observational trial.
All patients will be screened consecutively before undergoing kidney transplantation (KT).
All participants will undergo blood and urine sampling for estimation of CAF22 levels once before KT, once daily during the first 7 days after KT as well as at 2, 4 and 12 weeks after KT. Blood and urine sampling for CAF22 will be performed during routine follow-up sampling.
- Conditions
- Kidney Transplantation, Delayed Graft Function
- Being tested
- Blood and urine sampling
- Keywords
- Kidney Transplantation, Delayed Graft Function, C-terminal fragment of agrin, Dialysis
- Medical subject headings
- Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood and urine samplingOther
Blood and urine sampling (in the context of routine sampling)
| Study group | Role | What they receive |
|---|---|---|
| All study participants | Patients with end stage renal disease (ESRD) planned to undergo kidney transplantation. Receives: Other: Blood and urine sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delayed graft function (DGF) defined as the requirement of dialysis within 7 days after transplantation
Measured: 7 days
Secondary outcomes (3)
Immediate graft function (IGF)
Measured: 7 days
Need for hemodialysis
Measured: 7 days
Hemodialysis duration (in days)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2015 (estimated)
- Study start8 Oct 2014
- Primary completion27 Sep 2018
- Study completion27 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Spyridon Arampatzis, MD, Principal investigator, Dep. of Nephrology, Hypertension and Clinical Pharmacology, Bern University Hospital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02346968
- Sponsor's protocol ID
- 98/14
- Status last verified
- Aug 2019
- First submitted
- 20 Jan 2015
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Steubl D, Hettwer S, Vrijbloed W, Dahinden P, Wolf P, Luppa P, Wagner CA, Renders L, Heemann U, Roos M. C-terminal agrin fragment--a new fast biomarker for kidney function in renal transplant recipients. Am J Nephrol. 2013;38(6):501-8. doi: 10.1159/000356969. Epub 2013 Dec 14.
PubMed 24356308Steubl D, Hettwer S, Dahinden P, Wolf P, Luppa P, Wagner CA, Kuchle C, Schmaderer C, Renders L, Heemann U, Roos M. Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients. Transl Res. 2014 Nov;164(5):392-9. doi: 10.1016/j.trsl.2014.05.005. Epub 2014 May 16.
PubMed 24907476Steubl D, Hettwer S, Dahinden P, Luppa P, Rondak IC, Regenbogen C, Stock KF, Renders L, Heemann U, Roos M. C-terminal agrin fragment (CAF) as a serum biomarker for residual renal function in peritoneal dialysis patients. Int Urol Nephrol. 2015 Feb;47(2):391-6. doi: 10.1007/s11255-014-0852-5. Epub 2014 Oct 29.
PubMed 25352149Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997 Apr 15;63(7):968-74. doi: 10.1097/00007890-199704150-00011.
PubMed 9112349Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.
PubMed 19414839
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Serum and Urinary C-terminal Agrin Fragment-22 (CAF22) as Novel Renal Function Marker in Kidney Transplant Recipients - A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT02346968
- Acronym / sponsor ID
- 98/14
- Conditions
- Kidney Transplantation, Delayed Graft Function
- Keywords
- Kidney Transplantation, Delayed Graft Function, C-terminal fragment of agrin, Dialysis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 8 Oct 2014 (actual)
- Primary completion
- 27 Sep 2018 (actual)
- Study completion
- 27 Sep 2018 (actual)
- First posted
- 27 Jan 2015 (estimated)
- 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.
Established markers of kidney function, such as creatinine, have considerable limitations in the diagnosis of delayed graft function (DGF) after kidney transplantation (KT). Indeed, creatinine does not accurately reflect minor changes of renal function as its levels change only upon significant fluctuations of the latter. CAF22 is a molecule which arises from the degradation of a larger protein and it is proposed to be a reliable and more sensitive marker of renal function. This study aims to further clarify this issue by measuring blood and urine concentrations of CAF22 and comparing them with creatinine levels before and after KT.
The main assumption is that blood CAF22 levels could serve as a more sensitive kidney function biomarker than creatinine post-KT to detect DGF.
Detailed description
Background
Kidney transplantation (KT) is the most appropriate therapy of end stage renal disease (ESRD). While the number of kidney donors remained stable during the last decade the number of patients waiting for a kidney transplantation are rapidly increasing resulting in utilization of an increasing numbers of marginal renal transplants. These kidneys show a relatively high percentage of delayed graft function (DGF), which complicates post-transplant management and increases both the duration of initial hospitalization and the cost of transplantation.
Exact measurement of glomerular filtration rate (GFR) is complex in the clinical setting and thus GFR is usually estimated from serum creatinine levels through creatinine-based equations such as the MDRD or the CKD-EPI equations. Particularly, this is the case in kidney recipients with DGF, in whom creatinine levels remain high and they have to undergo dialysis. Creatinine is dialyzable, so that it cannot reflect the actual renal function in this setting due to fluctuations of its levels. Thus there is emergent need for a more accurate renal biomarker.
CAF22 is the C-terminal 22 kDa domain of agrin. Agrin is cleaved by its specific protease neurotrypsin at two distinct sites, whereas cleavage at the beta site generates a 22 kDa C-terminal fragment (CAF22). In the kidney agrin is part of the basal lamina, where it is the major contributor of the anionic potential of the glomerular basement membrane (GBM). There are indices for a proteolytic activity selectively shedding the C-terminal part of agrin of the GBM. Recently, a 19-fold increase of CAF22 levels in ESDR was observed, which was reduced in patients receiving KT, qualifying CAF22 as effective renal function marker. Additionally, current data support that CAF22 levels are not influenced by inflammatory processes, steroids or by hemodialysis with a standard dialysis membrane.
Objective
Primary:
- to compare CAF22 versus creatinine as biomarkers for DGF prediction in patients undergoing kidney transplantation
Secondary:
- to evaluate the kinetics of CAF levels related with the graft function outcomes "immediate graft function (IGF)" and "delayed graft function (DGF)"
- to elucidate whether CAF can make estimations on the required hemodialysis days of patients with delayed graft function
Methods
Research project with humans associated with the collection of biologic material and health-related data. Prospective, observational trial.
All patients will be screened consecutively before undergoing kidney transplantation (KT).
All participants will undergo blood and urine sampling for estimation of CAF22 levels once before KT, once daily during the first 7 days after KT as well as at 2, 4 and 12 weeks after KT. Blood and urine sampling for CAF22 will be performed during routine follow-up sampling.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All study participants | – | Other: Blood and urine samplingPatients with end stage renal disease (ESRD) planned to undergo kidney transplantation. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with end stage renal disease (ESRD) planned to undergo kindey transplantation in Bern University Hospital will be screened consecutively, informed and asked for written inform consent.
Key inclusion criteria (3 listed)
- Age ≥ 18 years old
- Written informed consent
- All patients planned to undergo kidney transplantation
Key exclusion criteria (3 listed)
- Age <18 years old
- Pregnancy
- Other individuals especially in need of protection (according to the Swiss Academy of Medical Sciences)
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 |
|---|---|---|
| Blood and urine samplingBlood and urine sampling (in the context of routine sampling) | Other | All study participants |
Primary outcome
Delayed graft function (DGF) defined as the requirement of dialysis within 7 days after transplantation
Time frame: 7 days
3 secondary outcomes
Immediate graft function (IGF)
Time frame: 7 days
Need for hemodialysis
Time frame: 7 days
Hemodialysis duration (in days)
Time frame: 7 days
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 28 Aug 2019.
- Background: PubMed 24356308Steubl D, Hettwer S, Vrijbloed W, Dahinden P, Wolf P, Luppa P, Wagner CA, Renders L, Heemann U, Roos M. C-terminal agrin fragment--a new fast biomarker for kidney function in renal transplant recipients. Am J Nephrol. 2013;38(6):501-8. doi: 10.1159/000356969. Epub 2013 Dec 14.
- Background: PubMed 24907476Steubl D, Hettwer S, Dahinden P, Wolf P, Luppa P, Wagner CA, Kuchle C, Schmaderer C, Renders L, Heemann U, Roos M. Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients. Transl Res. 2014 Nov;164(5):392-9. doi: 10.1016/j.trsl.2014.05.005. Epub 2014 May 16.
- Background: PubMed 25352149Steubl D, Hettwer S, Dahinden P, Luppa P, Rondak IC, Regenbogen C, Stock KF, Renders L, Heemann U, Roos M. C-terminal agrin fragment (CAF) as a serum biomarker for residual renal function in peritoneal dialysis patients. Int Urol Nephrol. 2015 Feb;47(2):391-6. doi: 10.1007/s11255-014-0852-5. Epub 2014 Oct 29.
- Background: PubMed 9112349Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997 Apr 15;63(7):968-74. doi: 10.1097/00007890-199704150-00011.
- Background: PubMed 19414839Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.
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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.
Spyridon Arampatzis, MD principal investigator
Dep. of Nephrology, Hypertension and Clinical Pharmacology, Bern University Hospital, Bern, Switzerland
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplantation and Delayed Graft Function, run by Insel Gruppe AG, University Hospital Bern at 2 sites in 2 countries.
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 3 inclusion and 3 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 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Switzerland. 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?
Delayed graft function (DGF) defined as the requirement of dialysis within 7 days after transplantation (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02346968, which also lists 5 linked publications.
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 28 Aug 2019.