Kidney transplantation is the treatment of choice for most patients with end-stage renal disease (ESRD). Strategies to increase donor organ availability and to prolong the transplanted kidney's survival have become priorities in kidney transplantation. Fifteen to 35% of all kidney transplant recipients will experience one episode of acute rejection in the first year. Options for treating these episodes include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. This review investigated the role of mono- or polyclonal antibodies (Ab) used to treat acute rejection in kidney transplant recipients. Twenty one trials (1387 patients) were included. Any antibody was better than steroid treatment for reversing the first acute rejection episode and preventing graft loss, but showed no significant difference in reversing steroid-resistant rejection episodes. Antibody-treated patients were 28 times more likely to experience an immediate reaction of fever, chills and malaise than those receiving steroid treatment. The main limitation of this review is that none of the included trials were performed using contemporary immunosuppressive regimens, with the most recent study performed in 2000.
In reversing first rejection, any antibody is better than steroid and also prevents graft loss, but subsequent rejection and patient survival are not significantly different. In reversing steroid-resistant rejection the effects of different antibodies are also not significantly different. Given the clinical problem caused by acute rejection, data are very sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardised reproducible outcome criteria are needed.
Registry data shows that between 15-35% kidney recipients will undergo treatment for at least one episode of acute rejection within the first post transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. In 2002, in the US, 61.4% patients with an acute rejection episode received steroids, 20.4% received an antibody preparation and 18.2% received both.
To determine the benefits and harms of mono- or polyclonal antibodies (Ab) used to treat acute rejection in kidney transplant recipients.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE (1966-June 2005), EMBASE (1980-June 2005), and the specialised register of the Cochrane Renal Group (June 2005).
Randomised controlled trials (RCTs) in all languages comparing all mono- and polyclonal antibody preparations, given in combination with any other immunosuppressive agents, for the treatment of acute graft rejection, when compared to any other treatment for acute rejection.
Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as risk ratio (RR) with 95% confidence intervals (CI).
Twenty one trials (49 reports, 1387 patients) were identified. Trials were generally small, incompletely reported, especially for potential harms, and did not define outcome measures adequately. Fourteen trials (965 patients) compared therapies for first rejection episodes. Ab was better than steroid in reversing rejection (RR 0.57, 95% CI 0.38 to 0.87) and preventing graft loss (death censored RR 0.74, CI 0.58 to 0.95) but there was no difference in preventing subsequent rejection or death at one year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection. There was no benefit of muromonab-CD3 over ATG or ALG in either reversing rejection, preventing subsequent rejection, preventing graft loss or death.