A patient in his 30s had been diagnosed with IgA nephropathy and had received standard-of-care treatment that initially included blood pressure control, angiotensin-converting enzyme (ACE) inhibitors, and omega-3 fish oil supplements. However, his kidney function continued to worsen. His nephrologist prescribed more-aggressive treatment including corticosteroids and immunosuppressive medications. Over time, the patient’s estimated glomerular filtration rate (eGFR) continued to decline until it was approximately 20 mL/min/1.73 m2.
At this point, the patient’s nephrologist referred him to Matthew Ellis, MD, a transplant nephrologist at Duke Medicine. “This patient's case highlights several important points we try to teach our patients about kidney transplant and living donation,” Ellis says. “Once his eGFR approached 20, his nephrologist made the referral to us. This is critical because when the eGFR drops below 20, we can put him on the deceased donor waiting list and also begin to identify living donors.”
It is advantageous to begin the evaluation and approval process for both deceased and living donor kidney transplant early. While the patient is accumulating time on the deceased donor waiting list, potential living donors may be identified and evaluated for compatibility. If a good living donor match is identified, transplantation can proceed at the optimal time for the patient, and the patient can potentially avoid dialysis altogether, Ellis explained.
The patient had already received several offers from potential donors, including a younger sibling and a friend. The sibling and the patient shared the same blood type, but his friend had a different blood type.
Which of these donors would you expect to be the best choice?
Answer: Although the patient’s sibling might be expected to be the best choice, further testing revealed that the patient’s friend was a better match.
Ellis and colleagues performed a human leukocyte antibody (HLA) cross match test to see whether the patient’s sibling would be a compatible donor. The test was positive, indicating that the patient had antibodies against his sibling’s kidney, even though they were biologically related. Ellis found that the patient’s friend was likely a better match, despite the facts that they were ABO-incompatible and not biologically related.
Blood group incompatibility has often been considered an insurmountable barrier to live kidney donation. However, researchers in Japan, where there is a very limited donor pool, have identified ways to modify apheresis and immunosuppressive protocols to manage the immune reaction that occurs early in ABO-incompatible transplants. Research has now demonstrated that if the initial immune reaction that occurs in the first weeks after transplantation of an ABO-incompatible kidney can be suppressed, that kidney will likely last longer and function better than an HLA-mismatched kidney with a positive cross match. Antibodies that develop to HLA-mismatched kidneys tend to persist, whereas the antibody response observed with ABO-incompatible kidneys usually diminishes after several weeks.
The patient had 2 apheresis sessions and received immunosuppressive drugs before receiving his friend’s kidney; he then had 2 apheresis sessions after the transplant. An aggressive immunosuppression protocol was initially required to ensure a successful outcome. “His kidney worked immediately,” Ellis said. “Every time we saw him in follow-up, we checked to see if he was reforming antibodies against his friend’s blood type, but he never did.” Ellis said the patient did develop several bacterial and viral infections related to the immunosuppression in the first 3 to 6 months after the transplant.
Because of diligent follow-up, however, the patient never had to be rehospitalized and was able to return to work 3 months after surgery. “He’s also an athlete who wanted to compete again, and I told him he could.”
Ellis said this case illustrates another important point—recipients should be counseled not to attempt to weed out potential living donors on their own. “There are many issues that patients might think are ‘problems’ that may not be problems at all or that we can actually work around, such as blood type.”