Clinical Pearls & Morning Reports
Published August 18, 2021
It is often difficult to ascertain a single cause of graft loss after kidney transplantation. Post-transplantation events such as acute rejection, viral infection, and cancer may be precipitated by nonmodifiable pretransplantation and perioperative factors related to the quality of the organ, cold ischemia time, and delayed graft function. Efforts to improve graft survival rates will need to focus on organ quality and the prevention and treatment of acute rejection, cardiovascular disease, infection, and cancer. Read the NEJM Review Article here.
Q: What is the immunosuppressive regimen most commonly used for kidney transplant recipients?
A: A combination of immunosuppressive medications targeting T cells is required to prevent kidney rejection and graft loss. The combination of mycophenolate mofetil, tacrolimus, and low-dose prednisone remains the most common immunosuppressive regimen for kidney transplant recipients worldwide.
Q: Are there any pharmacologic agents that reduce the incidence or severity of delayed graft function?
A: Some degree of renal perfusion injury is inevitable after kidney transplantation, but severe forms result in delayed graft function, defined as a requirement for dialysis in the first week after transplantation. Graft function is delayed in more than 25% of recipients of transplants from deceased donors. Delayed graft function augments graft inflammation and fibrosis and may accelerate graft dysfunction and lead to premature failure. To date, pharmacologic agents have not proved helpful in reducing the incidence or severity of delayed graft function.
A: Episodes of acute rejection, typically confirmed by kidney biopsy, are common after kidney transplantation. Rejection episodes may be T-cell–mediated, antibody-mediated, or both and are graded on the basis of the widely accepted Banff classification. Acute rejection, when discovered because of renal dysfunction, is referred to as clinical acute rejection, and subclinical rejection is diagnosed on the basis of surveillance biopsy. The incidence of clinical acute rejection and subclinical rejection during the first year after transplantation ranges from 10 to 15% and from 5 to 15%, respectively. Up to 40% of transplant recipients may have subclinical inflammation (borderline changes suggestive of rejection) during the first year after transplantation. Acute rejection negatively affects long-term survival, in accordance with the severity, persistence, and histologic type of rejection, and acute rejection that occurs more than 3 months after transplantation has a worse prognosis than acute rejection occurring earlier.
A: Cytomegalovirus (CMV) infection is the most common opportunistic infection after transplantation. CMV-seronegative patients are at increased risk for CMV infection if they receive a kidney from a seropositive donor. In addition, CMV infection is a risk factor for acute rejection and graft failure. Prevention, early recognition, and treatment of CMV infection are essential. Infection with BK virus is common in immunosuppressed kidney transplant recipients. BK virus infection starts as viruria, progresses to viremia, and if unchecked, leads to nephropathy and transplant failure. BK virus nephropathy is characterized histologically by a plasma-cell and lymphocytic-rich interstitial nephritis that may be difficult to distinguish from acute rejection unless viral inclusions are recognized. Such differentiation is critical, because successful treatment of BK virus infection requires early recognition and reduction of immunosuppressive therapy.