A Korean research team has presented a method to predict asymptomatic rejection, the biggest obstacle in kidney transplantation, using only a blood test. By identifying rejection risk through biomarkers in the blood of kidney transplant patients, the approach is expected to significantly reduce unnecessary biopsies.
Seoul National University Hospital announced on the 4th that a joint research team led by Professors Jo Ara and Min Sang-il of the Division of Vascular and Transplant Surgery, along with Professor Lee Ju-han of Severance Hospital and Professor Jung Cheol-woong of Korea University Anam Hospital, demonstrated that a donor-derived cell-free DNA blood test is useful for predicting asymptomatic rejection in patients who newly developed donor-specific antibodies (dnDSA) after kidney transplantation.
Transplantation is the only treatment for patients with end-stage renal failure, who must undergo lifelong dialysis because their kidneys can no longer perform their role of filtering waste from the body and excreting it as urine. However, "immune rejection," in which the immune system recognizes the transplanted kidney as a foreign invader and attacks it, has been the biggest obstacle. Donor-specific antibodies newly generated in the body after transplantation are cited as a major cause of declining kidney function and rejection. Yet rejection is actually confirmed in biopsies in only about 30 to 40 percent of patients who develop these antibodies. The remaining 60 to 70 percent had to undergo biopsies that carry significant burdens of bleeding, pain, and hospitalization—unnecessarily, out of concern for possible rejection.
Recently, "donor-derived cell-free DNA" (dd-cfDNA) has emerged in academia as an alternative. dd-cfDNA refers to DNA fragments released into the blood when a transplanted kidney comes under immunological attack or inflammation occurs. Although its potential as a non-invasive biomarker for detecting damage to the transplanted kidney in advance had been discussed, its clinical usefulness in deciding whether to perform a biopsy remained uncertain.
The research team conducted a comparative analysis of blood test and biopsy results in 123 patients who maintained stable kidney function after receiving kidney transplants at three domestic transplant centers. Of these, 77 were positive for donor-specific antibodies and the remaining 46 were negative.
As a result, the dd-cfDNA level in donor-specific antibody-positive patients was 1.2 percent (median), significantly higher than the 0.3 percent in negative patients. These levels tended to increase in proportion to the degree of microvascular inflammation inside the kidney. Applying the international biopsy diagnostic standard (Banff criteria), the cell-free DNA level (median) was 0.54 percent in patients with little or no microvascular inflammation in the kidney (inflammation score 0 to 1), but rose above 1.6 percent in patients with severe inflammation (inflammation score 2 or higher).
The team confirmed that while using donor-specific antibodies alone yielded an asymptomatic rejection prediction performance (AUC) of only 0.74, applying dd-cfDNA together significantly raised diagnostic performance to 0.82. In particular, they showed that the combined testing method using the two indicators can reduce unnecessary invasive biopsies and minimize procedural burdens on patients. When the cell-free DNA test was added to screen out patients with levels below 1.0 percent, the probability that these patients actually had no rejection (negative predictive value) reached 97.8 percent. By combining the two blood tests, the team established clinical grounds for effectively identifying the majority of low-risk patients and withholding unnecessary biopsies.
"When donor-specific antibodies are found after kidney transplantation, both patients and medical staff become concerned about rejection, but performing biopsies on all patients in the same way can be a burden," Professor Min explained. "This study showed that combining non-invasive biomarkers allows more precise screening of patients who are actually at high risk of rejection." He added, "Going forward, if cell-free DNA is appropriately integrated into the clinical decision-making process, it could develop into a personalized monitoring strategy that reduces patient burden while detecting damage to the transplanted kidney early."
The findings were published in the latest online edition of the International Journal of Surgery.
