Clinical operational tolerance after kidney transplantation

Area of Science:

• Transplantation immunology
• Clinical transplantation

Background:

• Achieving long-term allograft tolerance without immunosuppression is a significant challenge in transplantation.
• Clinical operational tolerance, defined by stable graft function off immunosuppression for years, is rarely reported, especially regarding patient history.

Observation:

• This study details the medical history of 10 kidney transplant recipients who maintained drug-free operational tolerance for an average of 9.4 years.
• Key clinical factors associated with this state were identified, including prolonged immunosuppression withdrawal periods and younger donor age (median 25 years).

Findings:

• Operationally tolerant recipients often exhibit low responses to blood transfusions (PRA 6 +/- 5.4%).
• The presence of anti-donor class II antibodies was observed in some tolerant patients.
• While most maintained function, two experienced renal function decline years after withdrawal, with one showing chronic rejection histology.

Implications:

• Understanding the factors contributing to operational tolerance can inform strategies for reducing long-term immunosuppression in transplant recipients.
• Identifying 'low responder' profiles and optimal donor characteristics may improve patient outcomes and graft survival.
• Further research is needed to elucidate the mechanisms underlying sustained tolerance and to predict potential long-term graft function decline after withdrawal.