Predicting Factors of Long-Term Results of OKT3 Therapy for Steroid Resistant Acute Rejection following Cadaveric Renal Transplantation

Abstract

In this retrospective study, we evaluated the histological and biological predictors of long-term response of renal transplant (RT) patients treated with orthoclone OKT3 for steroid resistant acute rejection (AR). Seventy-three patients, aged 37 ± 12 years, were included in this study between March 1987 and December 1996. All the patients but one had received sequential quadruple immunosuppression (polyclonal antilymphocyte globulins; steroids; azathioprine, and cyclosporin A). OKT3 (5 mg/day for 10 days) was administered for biopsy-proven steroid resistant AR i.e., after 3 consecutive pulses of methylprednisolone (10 mg/kg each). This was the first AR in 46 cases, the second AR in 22 cases and the third AR in 4 cases. Renal histology (Banff) showed borderline (BL) changes in 18 patients, grade I AR in 28 patients; grade II AR in 22 patients, and grade III AR in 5 patients. When treatment with OKT3 commenced (107 ± 18 days post-transplantation) the mean serum creatinine (SCr) level was 325 ± 195 μmol/l; this had decreased to 191 ± 106 μmol/l by the end of OKT3 therapy. The immediate response to OKT3 therapy i.e., within the first month, was not dependent on the histological score. Twenty-six patients (35%) subsequently experienced at least one more AR episode of whom 4 were retreated with OKT3. The overall patient’s survival was 94.5% at last follow-up. The overall cumulative graft survival was 64.5% at 2 years, 52.5% at 5 years, and 40.5% at 8 years. The graft survival (5 years) tended to depend on the initial histological score, i.e. BL 30%; grade I 66%; grades II and III 55.5% (p = 0.08). In a multiple logistic regression analysis we tried to identify independent factors that would predict that a graft would still be functioning at least 2 years after OKT3 therapy. We therefore analyzed the following parameters: donor and recipient’s age; gender; cold ischemia time; HLA matching; panel reactive antibodies (PRA) prior to grafting; previous transplantation(s); total number of AR episodes; the time of onset of the AR treated by OKT3 compared to the other AR; the time of onset of the AR treated by OKT3; SCr levels at days 0, 10 and 30 after OKT3 therapy; histological score (Banff) i.e., the magnitude of AR and the presence or absence of chronic lesions. The only independent factors which would predict that a graft was still functioning 2 years after OKT3 therapy were: PRA <25% (Odds ratio (OR) 7.68 (1.15–51.3); p = 0.035); a grade I AR (OR 10.52 (1.18–93.5); p = 0.035); SCr level 1 month after OKT3 therapy (OR 0.935 (0.87–1.002); p = 0.05). HLA matching and the presence of histological chronic lesions were nearly significant (p = 0.06 and 0.09 respectively). In conclusion, this retrospective study shows that independent predictors of the long-term response to OKT3 therapy for AR in RT patients are the magnitude of pre-transplant PRA, the histological score, and the SCr level one month after OKT3 therapy.

Clinical and Molecular Profiling to Develop a Potential Prediction Model for the Response to Alemtuzumab Therapy for Acute Kidney Transplant Rejection

“…The ALEMAR score included several predictors that were previously associated with a good response to other (non-alemtuzumab) AR treatments, such as an early timing of AR, higher recipient age, and a high baseline eGFR. [27][28][29][30][31][32] Timing of rejection in particular seems to play an important role in the response to alemtuzumab, as reflected in the hardly overlapping ranges in timing between responders and nonresponders (Table 1). It was also found that a double alemtuzumab dose and the treatment indication "severe AR" were related to a higher chance of response.…”

OKT3 Therapy in Addition to Tacrolimus Is Associated with Improved Long-Term Function in Patients with Steroid Refractory Renal Allograft Rejection

“…Rostaing et al [2] analyzed long-term outcome of 73 patients with steroid-resistant acute rejection after treatment with OKT3. The baseline immunosuppressive therapy was not changed and patients were generally treated with a combination of cyclosporine, azathioprine and steroids.…”

“…The study did not show differences in terms of recipient age, gender, HLA mismatch, or chronic lesions or grade II and III rejection in histology. Therefore, the study of Rostaing et al [2] indicates a predictive value for the histological findings of preconversion biopsies in steroid-resistant rejection. Furthermore, the presence of chronic rejection has been reported to worsen prognosis in steroid-resistant rejection [12].…”

“…Although its overall rate has decreased during recent years, acute renal allograft rejection continues to be a serious problem impacting on long-term allograft survival by increasing the rate of chronic rejection [1]. Acute rejection is usually treated by glucocorticoid (‘steroid’) pulse therapy, the overall reversal rate ranges between 74 and 100% [2]. Reversal rates may be lower if acute cellular rejection is accompanied by vascular and/or chronic rejection [3, 4].…”