The use of steroids remains the proven standard of care for renal transplant patients. Its use has been associated with a myriad of metabolic adverse effects (well known to the reader), which, in turn, has motivated many transplant patients to request their discontinuation. Despite the initial encouraging news from small, single-center studies, the largest prospective, randomized, long-term (>5 years) trial to date failed to show a significant metabolic benefit from steroid avoidance/minimization (1). In addition, steroid withdrawal studies have been characterized by a high incidence of biopsy-confirmed mild acute rejection (Banff 1a and 1b). These findings have been more pronounced in patients at high immunologic risk (e.g., the young; patients of black race) and are primarily seen with delayed and slow steroid tapers (carried out >6 months from the time of transplantation). As a result of this experience and the introduction of more potent immunosuppressants such as antithymocyte globulin, anti-CD25 antibodies (daclizumab and basiliximab), and anti-CD52 antibodies (alemtuzumab), slow steroid withdrawal protocols have been replaced by protocols in which steroids are minimized or avoided. The avoidance protocols in particular are characterized by either no corticosteroid therapy or the full elimination of steroids within 7 days of transplantation. A recent US analysis from the Scientific Registry of Transplant Recipients concluded that patients who are on steroid avoidance therapies do not have a worse outcome compared with patients who are on maintenance steroids regimens (2). A recent discussion of this retrospective analysis concluded that despite a possible selection bias, the findings were indicative that patients could be safely discharged on a steroid-free regimen (3). The development of interstitial fibrosis and tubular atrophy (so-called chronic allograft nephropathy) and a higher incidence of more severe rejection (Banff 2a) has been identified in long-term avoidance steroid studies (1). In some cases, it may take as long as 5 years to see renal allograft function impairment in patients who receive a steroid avoidance regimen (4). The aim of the study by Schold et al. was to determine which factors are associated with the failure of transplant patients to remain free of steroid therapy 6 months after transplantation. They used multivariate logistic regression and Kaplan-Meier and Cox proportional hazard models to evaluate patient and graft survival from deceased- and living-donor recipients. In their study of >80,000 patients, they categorized the transplant recipients into three groups (N = 84,647): (1) Patients who received steroids uninterruptedly after transplantation (n = 60,429 [71%]), (2) patients who received no steroids since transplantation (n = 18,591 [22%]), and (3) patients who were started on steroids after a 6-month steroid-free period (n = 5627 [7%]). They obtained their information from the Scientific Registry of Transplant Recipients data system focusing on the period from 2002 through 2008. Findings. Patients who remained steroid-free were more likely to be characterized as having low immunologic risk (e.g., living-donor transplant recipients, white patients, unsensitized, primary transplant recipient). Among the risk factors implicated in the resumption of steroids among deceased-donor recipients were black race, high sensitization, HLA mismatching, retransplantation, and recipients of organs from older donors; these patients were identified as having high immunologic risk. A similar trend was observed for living-donor recipients who resumed steroids 1 year after transplantation, in which factors including donor age >60 years, high sensitization, less preemptive transplantation, greater likelihood of an unrelated donor, increased HLA mismatching, and retransplants were noted. Graft survival was not different between the steroid avoidance group and those who were maintained on corticosteroids (adjusted hazard ratio [AHR] 1.01; 95% confidence interval [CI] 0.96 to 1.07). Conversely, the need to resume steroid therapy was clearly detrimental to the outcome of the renal allograft (AHR 1.20; 95% CI 1.11 to 1.29) and to patient survival (AHR 1.17; 95% CI 1.06 to 1.29). There was no statistical difference between deceased-donor and living-donor recipients. Induction therapy with alemtuzumab and the use of tacrolimus were associated with a lesser need for initiation of steroids at 6 months. Lastly, there was a suggestion (P < 0.001) of a center effect regarding the use of a steroid-free protocol and resumption of steroid therapy. Commentary. The introduction of more potent immunosuppressive agents (anti-thymocyte globulin, alemtuzumab, tacrolimus) has facilitated the long-sought development of steroid-free/minimization regimens; however, this management approach should be individualized. On the basis of the study findings of Schold et al., until the long-term safety and efficacy of steroid minimization strategies are validated (by controlled clinical trials with adequate long-term follow-up), the use of steroid avoidance/minimization protocols in patients at high immunologic risk—characterized by black race, a high degree of sensitization (panel-reactive antibody >30%), HLA mismatching, retransplants, and organs from older donors—should be discouraged.
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Oct 2, 2023
Christina Hartje-Dunn + 6
Open Access