Kidney Transplant Failure and Rejection Clinical Trial
Official title:
Research on the Detection of Donor Derived Cell Free DNA (cfDNA)for the Early-stage Diagnosis of Acute Rejection Reaction Post Kidney Transplantation
Acute rejection (AR) is still one of the major complications after kidney transplantation. The current diagnosis measure for AR is primarily pathological puncture test and hematuria biomarker detection, yet due to their inferior performance on timeliness, the allograft kidneys usually have been in severe conditions when the diagnoses take place. Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for "liquid biopsy", it can predict acute rejection at very early periods, and it is easy to operate, with fewer invasive injuries, and can reflect related conditions in a timely manner, etc.. This study plans to utilize second-generation sequencing technology to systematically evaluate the abundance variations of nuclear genome and mitocondria derived dd-cfDNA in the kidney transplant recipients' blood and urine, thus it can assist in accumulating more proof for the clinical utilization of dd-cfDNA from different sources at the early stages of AR in evidence-based medicine, and lay foundation for the development of dd-cfDNA based early-stage rejection detection tools afterkidney transplantation surgery.
With the growing development of kidney transplant technologies and immunosuppressive
therapies, the number of end-stage renal disease patients receiving kidney transplant has
been increasing. Acute rejection (AR) is one of the main complications for kidney
transplantation, and AR is the major reason for lowering graft survival rate and for graft
malfunction, thus the timely detection of AR and early interventions are crucial. The current
clinical measures for the detection of AR include pathological puncture test and hematuria
biomarker detection. Yet pathological tests are invasive, limited to sampling errors and the
existing perception differences among observants, and with other disadvantages such as
expensiveness, poor patient compliance, and related complications. Hematuria biomarker
detection is slow in response and low in the sensitivity and specificity for reflecting the
organs' metabolic index in the diagnosis of acute rejection injury. Though the monitoring of
immunosuppressant drugs, immune molecules and cytokines in the blood circulation can both
provide certain value for the evaluation of patients' immune status after organ transplant,
these factors are not good indicators for the early-stage diagnosis of allograft injury.
Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for "liquid biopsy", it is
easy to operate, with less invasiveness, and it can reflect related conditions in a timely
manner, etc.. This measure can detect the injury degree for allograft, and the index will
rise before fluctuation reflection of the syndrome and related laboratory indexes, which is
crucial for the very early-stage diagnosis of allograft acute rejection, and the further
prevention of allograft injury. In the mean time, dd-cfDNA assumes high utilization value for
the monitoring of immunosuppressive conditions, and therefore providing instructions for the
optimization of the immunosuppressive treatment.
Under the condition of signed informed consent, the study protocols were scheduled as below:
Self-control study protocol:
20 to-receive-kidney-transplant patients are randomized, the self-control study protocol is
utilized for each patient as the following.
Before the kidney transplant surgery, 1ml of peripheral EDTA anticoagulant from the
recipients, and 1ml of peripheral EDTA anticoagulant from the donors are collected.
In 1 week, 2 weeks, 3 weeks' time after the kidney transplant surgeries, 8 to 10 ml of
peripheral blood from the recipients using cfDNA blood collection tubes, and 10 to 15 ml of
midstream urine are collected respectively.
Inclusion criteria:
*Patients are suitable for kidney transplant surgeries.
Exclusion criteria:
- Patients have failed in the transplant surgeries.
- Patients have no urine 1 week after the transplant surgeries.
- Patients have severe infectious complications after the transplant surgeries. b, Case
group: For 20 patients that have been diagnosed with acute rejection on the first
visits, 8 to 10 ml of EDTA anticoagulant, 10 to 15 ml of midstream urine, 5 ml of saliva
are collected before the treatment, 1 week and 2 weeks after the adjustment of the
anti-rejection treatment, 8 to 10 ml of blood using cfDNA blood collection tubes, 10 to
15 ml of midstream urine, 5 ml of saliva are collected respectively.
Inclusion criteria:
Control group:
- The allograft kidneys function normally.
- The rejection of allograft kidneys are excluded.
- The patients have no infectious complications.
Case group:
- There is obvious evidence for acute rejection of the allograft kidneys.
- The patients have no infectious complications.
Exclusion criteria:
- The patients have infectious complications.
- The patients have tumors.
- The patients are pregnant.
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