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Steroid withdrawal, rejection and the mixed lymphocyte reaction in children after renal transplantation
Insights
Pediatric kidney transplant patients can discontinue steroid therapy, but some experience rejection later. Immunoresponsiveness testing revealed complex allograft tolerance patterns, challenging previous hypotheses.
Area of Science:
- Nephrology
- Immunology
- Pediatric Transplantation
Background:
- Cardiovascular mortality is a leading cause of death in renal transplant recipients.
- Chronic corticosteroid therapy contributes to hyperlipidemia and hypertension post-transplantation.
- Reducing cardiovascular risk factors is crucial for long-term outcomes in pediatric renal allograft recipients.
Purpose of the Study:
- To evaluate a steroid withdrawal protocol in pediatric renal transplant recipients.
- To assess the rate of acute rejection episodes after steroid discontinuation.
- To investigate immunoresponsiveness using in vitro methods to understand allograft tolerance.
Main Methods:
- A steroid withdrawal protocol was implemented, transitioning patients to cyclosporine monotherapy.
- Acute rejection episodes were monitored after steroid taper completion.
- Mixed lymphocyte culture reactions were used to assess donor-specific hyporesponsiveness and tolerance.
Main Results:
- 36 of 67 patients successfully discontinued prednisone.
- 22 of these 36 patients experienced acute rejection, with a mean onset of 14 months post-withdrawal.
- 14 patients remained rejection-free for a mean of 70.3 months.
- Mixed lymphocyte culture results showed unexpected patterns of responsiveness and tolerance, challenging the initial hypothesis.
Conclusions:
- Steroid withdrawal in pediatric renal transplant recipients can be achieved but carries a risk of late acute rejection.
- Immunoresponsiveness testing revealed complex donor-specific immune responses, indicating that tolerance is not solely dependent on steroid independence.
- Further research is needed to elucidate the mechanisms underlying allograft tolerance and optimize immunosuppression strategies.
Abstract:
With improved long-term graft survival after renal transplantation, cardiovascular mortality is emerging as the leading cause of death in adults and is also being reported in children. Chronic corticosteroid therapy is thought to be an important cause of post-transplant hyperlipidemia and hypertension. This study describes a steroid withdrawal protocol initiated to reduced cardiovascular risk factors in pediatric renal allograft recipients, reports on the rate of rejection observed and the use of an in vitro method to measure immunoresponsiveness and identify those patients who have not experienced a rejection episode. Thirty-six of 67 patients were able to discontinue prednisone and were maintained on cyclosporine alone. Twenty-two of the 36 patients experienced an acute rejection episode a mean of 14 months (range 1.5 to 36 months) after completion of the steroid taper. Ten of the 22 rejections occurred within 12 months after completion of the taper. Fourteen patients remain rejection free to date for a mean of 70.3 months (range 19 to 111 months) after withdrawal. Using the mixed lymphocyte culture reaction, we tested the hypothesis that steroid dependent recipients (SDR) will express donor antigen specific responsiveness and steroid independent recipients (SIR) will exhibit donor antigen-specific tolerance. Four of seven SDR were tolerant to donor specific antigens but responsive to unrelated controls, while five of six SIR were responsive to donor specific antigens. These unanticipated results highlight the complexity of allograft tolerance.