Emphasis on donor-specific antibody testing for long-term survival of the transplanted kidney

  Kidney transplantation has gone through half a century today. For half a century, kidney transplantation as a treatment for end-stage renal failure has given new life to numerous uremic patients. The development of surgical techniques, the advancement of immune rejection theory and the emergence of new immunosuppressive agents have greatly reduced acute rejection and hyperacute rejection in the early postoperative period, and greatly improved the survival rate of both human kidneys 1 year after surgery. It is the development of these technologies that has led kidney transplantation to the clinic as one of the conventional methods for the treatment of end-stage renal failure.  Modern immune rejection studies have shown that the probability of rejection after surgery is directly related to the level of antibodies present in the preoperative transplant recipient and to the degree of HLA matching between the donor and recipient. Therefore, all transplant centers attach great importance to the screening of patients’ preoperative antibody levels, especially the anti-HLA antibody test, FLOW-PRA. For transplant recipients with preoperative HLA antibody levels within the normal range, they are usually considered low-risk patients for rejection, and if such patients are successfully matched, then transplantation can be performed. Patients with preoperative antibody levels above normal, especially those with antibodies against the donor locus on further screening, are considered high-risk for postoperative rejection or even over-rejection. For these patients, antibody levels must be reduced before kidney transplantation, especially for the specific donor gene loci, to below safe levels before the procedure can be performed. If a high level of FLOW-PRA before surgery can be compared to the presence of a large army of antibodies against the allogeneic body, then the presence of DSA can be interpreted as a special force in this army, which is often The special forces often perform “targeted killing” operations. Because DSA acts at the site of the donor kidney, the presence of DSA in the transplant recipient before surgery will result in a direct attack of these antibodies on the transplanted kidney after surgery, causing severe rejection, even hyperacute rejection. Modern studies have shown significant differences in the incidence of rejection and long-term survival of the transplanted kidney in patients with preoperative DSA, with the incidence of acute antibody-mediated rejection exceeding 35% in patients with preoperative DSA and graft loss in more than 15% of patients within 1 year after surgery. In contrast, the probability of acute antibody-mediated rejection in patients with preoperative DSA-negative was <5%.  However, in contrast to the increasing short-term human kidney survival rate, the long-term survival of transplanted kidneys has hovered at a low level. Chronic humoral rejection or chronic antibody-mediated rejection is the main reason for this. In patients with a negative preoperative FLOW-PRA, then, there is still the possibility of new antibody production after surgery. And the newly produced antibodies after surgery can often mediate chronic humoral rejection. In patients with negative preoperative antibodies, new antibodies are produced in about 10-20% of patients in the first year after surgery and in about 3-4% of patients each year thereafter. Some of these newly generated antibodies are donor-specific, i.e. DSA, and current studies have shown that these newly generated antibodies, especially DSA, cause persistent damage to the transplanted kidney, resulting in antibody-mediated rejection. This is also the reason why the long-term survival rate of the transplanted kidney has been hovering at a low level.  There is a temporal relationship between new postoperative antibody production, especially DSA, and graft injury, impaired graft function and ultimately graft loss. Antibody production precedes creatinine elevation. In patients with new postoperative antibody production, the antibody continues to mediate graft injury, causing antibody-mediated rejection, and within a certain period of time, due to the compensatory function of the transplanted kidney, the creatinine does not rise clinically, but as the transplanted kidney injury continues to a certain stage, the creatinine rises clinically and eventually leads to graft loss.  Studies have shown that regular monitoring of postoperative antibodies and treatment of patients with newly generated antibodies, especially DSA, can partially or even completely remove antibodies, alleviate graft injury and significantly prolong graft survival.  Therefore, it is important to monitor postoperative antibodies. Modern studies have shown that the frequency of antibody monitoring is not the same for different individuals, and the method of monitoring is also important. Briefly, for patients with negative preoperative antibodies, antibody testing can be performed 2-3 times in the first year after surgery and once a year thereafter. For patients who have newly developed antibodies after surgery, antibody testing should be performed every 6 months.  It is also important to have a good test method with high sensitivity and accurate loci screening, especially for DSA. Most of the transplant centers in China are only able to perform FLOW-PRA, which is a test for antibody levels, but not for antibody loci, and therefore cannot accurately identify DSA. examination, and is currently one of the few units in China that can perform antibody subdivision and DSA detection. The use of the new method for DSA detection, early detection of DSA and corresponding de-antibody treatment has benefited many patients in clinical practice.