Corticosteroid avoidance in adult kidney transplant recipients under rabbit anti-T-lymphocyte globulin, mycophenolate mofetil and delayed cyclosporine microemulsion introduction

Abstract

SummaryWe conducted the first prospective, randomized, open-label multicenter study in low-immunologic risk adult recipients of primary cadaver kidney transplants receiving rabbit anti-T-lymphocyte globulin, mycophenolate mofetil, cyclosporine microemulsion introduced on day 5, with and without corticosteroids. Patients were randomly assigned according to age and cold ischemia time to receive corticosteroids for at least 6 months or no corticosteroids at all. The main efficacy evaluation criterion was acute rejection (including all treated episodes and those biopsy-confirmed) during the first year following transplantation. For this purpose, this report includes the actual results of the whole 12-month follow-up of all randomized patients. For efficacy analysis, 98 patients were evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group. Taken as a whole, 81% of the patients (n = 159) never received anti-rejection treatment. From the 38 patients who received antirejection treatment, 25 (25.5%) were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy-proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs. 3) were not considered as biopsy-proven acute rejections. Onset of first rejection was significantly shorter in the Steroid avoidance group (P < 0.027). First-line anti-rejection treatment response, need for any rescue therapy, as well as histologic severity of rejection episodes did not statistically differ between the groups. One-year post-transplantation analysis showed no differences in delayed graft function, serum creatinine, creatinine clearance, 24-h proteinuria, as well as serious adverse events between the groups. De novo diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed malignancies (P < 0.059) were however more frequently observed in the Steroid maintenance group. At the end of the first post-transplant year, 99% of patients in the Steroid avoidance group and 97% of patients in the Steroid maintenance group were respectively alive (P = 0.34), with respectively 95% and 93.2% of functioning kidney grafts (P = 0.62). Our results showed Transplant International

Early Corticosteroid Avoidance in Kidney Transplant Recipients Receiving ATG-F Induction: 5-Year Actual Results of a Prospective and Randomized Study

“…The study was conducted in accordance with the Declaration of Helsinki, Declaration of Istanbul and Good Clinical Practice. Further details of the design, randomization procedure and statistical methodology are available in the 1-year report which specifically addressed the prespecified primary end point of acute rejection (17). All eligible patients were randomized to ÀCS or þCS before transplantation using block randomization (block size: 4) and an allocation ratio of 1:1, with stratification according to center, age ( 50 or >50 years) and cold ischemia time ( 24 or >24 h).…”

Immunology of Transplant Protocols

“…Myriad toxicities such as sodium and water retention, hypertension, adipose weight gain, hyperglycemia, dyslipidemia, and osteoporosis have led to the development of immunosuppressive protocols that spare or avoid corticosteroids. These protocols usually require induction with a lymphodepleting monoclonal antibody or polyclonal serum to minimize the risk of acute rejection [27,28]. However, early corticosteroid withdrawal may not always be as effective in preventing acute rejection, as suggested by a retrospective analysis of a large cohort of liver transplant recipients [29].…”

Modern Immunosuppression Regimens in Kidney Transplantation

“…Our transplant center's experience utilizing induction therapy to enable steroid withdrawal has been very successful in a diverse population, using rATG in the majority of patients [102] and basiliximab in well-matched living donor recipients [61]. In a study by Cantarovich et al, patients administered rATG and steroid-maintenance immunosuppression had significantly lower acute rejection rates compared to patients on a steroid-free immunosuppression regimen, although the incidence of malignancy, de novo diabetes, and hyperlipidemia were higher in steroid-maintenance group [103]. Patient survival, graft survival, and infection rates were not significantly different between the two groups at 1 year.…”