A Game-Changer in Kidney Transplant Care


Kidney transplants save lives, but monitoring graft health is key! Plasma creatinine lacks sensitivity for early detection, but donor-derived cell-free DNA (dd-cfDNA) is emerging as a game-changing, non-invasive biomarker.

Donor-derived Cell-free DNA: A Game-Changer in Kidney Transplant Care
Highlights:

  • Traditional biomarkers used in kidney transplant care lack sensitivity and specificity for early detection
  • Donor-derived cell-free DNA is used as a biomarker for detecting early graft rejection or inflammation
  • dd-cfDNA is a minimally invasive method for monitoring transplant health status

Kidney transplants can treat chronic kidney disease or end-stage renal disease and improve survival rates. A healthy kidney from a living or dead donor is transplanted to recipients who need it (1 Trusted Source
Donor-Derived Cell-Free DNA: Kidney Transplant Health Biomarker

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After transplantation recipients undergo rigorous post-transplant monitoring to ensure the long-term success of the graft and to detect complications like acute rejection and infection.

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Traditional Biomarkers for Kidney Transplant

Kidney graft functioning monitoring is based on biomarkers such as plasma creatinine, urine output and biopsy.

Plasma creatinine, commonly used to monitor kidney function lacks specificity and sensitivity for early detection. Creatinine levels are delayed in response to kidney injury and they do not reflect small changes in graft function.

Although histological examination through biopsy is the gold standard for diagnosing acute rejection, it is invasive, time-consuming, expensive, and carries risks of complications such as bleeding or infection.

The need for non-invasive biomarkers to monitor transplant health is growing.

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Donor-derived Cell-free DNA

Donor-derived cell-free DNA (dd-cfDNA) is a fragment of DNA released from the donor’s organ into the recipient’s bloodstream after the transplant. dd-cfDNA is a key biomarker of graft injury with levels increasing due to damage or inflammation.

In kidney transplants elevated dd-cfDNA levels can be an indication of acute rejection, inflammation or graft dysfunction. dd-cfDNA is primarily detected in blood and urine. Clinicians can use blood plasma or serum as a minimally invasive approach to monitor transplant status.

dd-cfDNA is detected by polymerase chain reaction (PCR) based techniques, digital PCR and next-generation sequencing (NGS). These methods quantify the proportion of dd-cfDNA relative to total cfDNA which shows the extent of graft injury.

dd-cfDNA serves as a direct reflection of graft health. When the transplanted kidney is damaged due to acute rejection, inflammation or ischemia donor-derived cells release fragments of DNA into the recipient’s bloodstream.

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Advantages of dd-cfDNA

Studies have shown a strong correlation between elevated dd-cfDNA levels and graft rejection or dysfunction.

dd-cfDNA levels rise quickly in response to graft malfunction often before plasma creatinine helps in early detection.

dd-cfDNA is specific to the donor organ and is a direct marker of graft injury, improving the sensitivity of monitoring.

It is a minimally invasive method where dd-cfDNA is detected through simple blood or urine tests reducing the need for biopsies.

dd-cfDNA is a promising minimally invasive biomarker for kidney transplant monitoring, guiding clinical decisions and reducing dependence on invasive biopsies. While challenges like cost and standardization remain, continued advancements are expected to make dd-cfDNA a transformative tool in transplant care and improve long-term benefits.

Reference:

  1. Donor-Derived Cell-Free DNA: Kidney Transplant Health Biomarker – (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1485905/abstract)

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