Chronic kidney disease (CKD) is caused by progressive deterioration of kidney function due to loss of functional units in the kidneys. Once a large proportion of the functional units have been lost, the patient reaches end-stage renal disease (ESRD). The only option for treating ESRD patients is dialysis, a procedure performed while the patient is waiting for a new kidney from a matching donor. The availability of donor kidneys from living or deceased donors is scarce, and patients often wait for years before a matching donor is found.

 

How many people need a kidney transplant?
In Europe, there are several transplant waiting lists such as Eurotransplant, ScanTx and others. In 2016, there were 10.901 patients on the waiting list at Eurotransplant and 2.027 patients at ScanTx. The scarce number of available donor kidneys results in long waiting lines, and about half of patients are on the waiting list for 2to 4 years, while a third of patients are on the waiting list for 5 or more years. Based on 2019 data, 71.320 kidney transplants were performed in the regions: Americas, Europe, Africa, Eastern Mediterranean, and Western Pacific.


Source

How are recipients and donors matched?
Potential recipients of a donor kidney are identified based on general criteria such as blood type, length of time on the waiting list, whether the recipient is a child, whether the height of the donor and recipient are a good match, and the severity of the patient's health condition. Other factors used for kidney allocation include a negative lymphocytotoxic crossmatch, the number of HLA antigens shared by the donor and recipient based on tissue typing, and the patient not having a current infection. When matching organs from deceased donors to patients on the waiting list, many of the factors considered are the same for all organs.

How are patients who receive a kidney transplant treated?
Patients receiving a kidney transplant are treated with immunosuppressive treatments (anti-rejection medications). Immunosuppressive treatment of transplant recipients always carries the risk of over-immunosuppression, which has been shown to increase the risk of infections and malignancies, and thus patient mortality.

Medications for rejection after kidney transplantation include:


Careful evaluation of renal transplant recipients is important for a successful transplant outcome. With advances in treatment, most allografts are no longer lost to acute rejection of the allograft by the renal transplant recipient. The incidence of acute rejection within the first year after transplantation has decreased significantly over the years and is currently 7-10%.

However, due to other factors such as the underlying cause of ESRD and immune-mediated injury, early fibrosis of the allograft is very common. This is evident from studies showing that tubulointerstitial fibrosis and tubular atrophy was detectable in 40% of patients within 6 months and increased to 65% of recipients within 2 years. Renal transplantation is therefore not a long-term solution, and transplanted patients have an average of 10-15 years before they regain ESRD.

At this point, patients restart renal replacement therapy (including dialysis) and return to the transplant waiting list. In addition, studies have shown that the donor kidney from the second transplant has a significantly lower survival rate than the first transplant. This underscores the need to find new ways to improve recipient-donor matching in kidney transplantation, or to develop new effective treatments that either alleviate the cause of ESRD or directly inhibit the processes that destroy the functional units of the kidneys.

Previous meta-analyses have shown that risk prediction models for graft failure primarily consider recipient age, gender, and comorbidities. While clinical parameters are widely used to evaluate renal transplant recipients, validated biomarkers are lacking. Because renal fibrosis is a strong independent predictor of future renal function loss, assessment of the recipient's fibrosis activity and burden could help clinicians decide on the treatment plan and serve to assess the effect of potential antifibrotic treatments.

Visit our kidney biomarker portfolio and choose a panel that fits your clinical research or drug development targets!


Rasmussen et al Scientific Reports, 2017

 

There is an urgent need for improved characterization of renal transplant recipients, as currently neither clinical parameters nor biomarkers are available to accurately predict immediate and long-term renal function after transplantation. Preliminary results suggest that the marker PRO-C6 has the potential to fill this gap.

The goal of the PRO-C6-Rec project is to develop a breakthrough in vitro diagnostic (IVD) device that could improve the allocation of a scarce pool of donor kidney transplants to suitable recipients. As part of the project, we will investigate how PRO -C6 relates to various aspects in transplantation, such as histological changes and outcome. A successful project could lead to a tool that reduces the number of patients returning to the transplant waiting list (see Figure 2).

The project will develop a noninvasive IVD to measure VI type collagen formation, the PRO-C6 test, which meets the technical requirements equivalent to a CE marker. If successful, the PRO-C6 test will be able to reflect the state of the graft over time and predict rejection and other adverse outcomes.


Why is the project being carried out?

The PRO-C6-Rec project is investigating the potential clinical utility of the PRO-C6 test. The project is investigating various aspects such as the histological association of PRO-C6 with fibrosis and inflammation in biopsies from clinical centers in the Netherlands and France (see Figure 3). Specifically, the project is investigating:

- The association of PRO-C6 with:

  • Disease progression and adverse outcomes
  • Markers of pathology
  • Disease Severity

- How treatment affects PRO-C6 levels in kidney transplant recipients

- How PRO-C6 levels change over time

Please don't hesitate to contact us if you have any questions or other inquiries.

Are you interested in learning more about Nordic Bioscience?
Enter your information in the form and a representative will contact you shortly.

By submitting this form you agree to our terms and conditions.