1,081 renal transplant patients in this multicentre prospective randomised trial were primarily monitored for development of posttransplantion diabetes mellitus (PTDM) after initial treatment with prolonged-release tacrolimus, basiliximab, MMF and either intraoperative bolus steroids in arm 1, or the same treatment including continued steroid administration tapered by day 10 in arm 2. Patients followed for 24 weeks for PTDM development did
not show differences in PTDM incidence, and the incidence was generally low in both groups, but arm 2 did show significantly (5-7%) more transplant rejection episodes. Therefore, this reduced steroid use protocol results in relatively low PTDM rates, but treatment with only intraoperative steroids poses a substantial risk for increased transplant rejection; a short 10-day course of steroids does reduce this rejection risk, without apparently increasing the PTDM risk. Importantly, this study was conducted in a lower risk, primarily Caucasian population, so these results cannot be directly extrapolated to different or higher risk transplant recipients. This study does suggest that patients at high risk for PTDM could benefit from this strategy of early steroid tapering.
Kulkarni, S., Kirkiles-Smith, N. C., Deng, Y. H., Formica, R. N., Moeckel, G., Broecker, V., Bow, L., R, T., Js, P.
American Journal of Transplantation. 2016;[record in progress]
Aims:To determine whether prolonged treatment with eculizumab would stabilize graft function in kidney transplant recipients that had developed de novo donor specific antibody (DSA).
Interventions:Participants were randomized to receive either eculizumab for 6-months followed by observation for 6-months (treatment group), versus observations over a 12-month period (control group).
Participants:16 patients aged 18-65 years, > 6-months from their first kidney transplant with a measured de novo DSA of greater than Mean Fluorescence Intensity (MFI)>1100.
Outcomes:The primary outcome measured was the difference in percent change of estimated glomerular filtration rate trajectory over time. Secondary outcomes included 1-year graft survival, incidence of biopsy-proven acute rejection, incidence of treatment failure and expression of endothelial cell associated transcripts (ENDATs).
Follow Up:12 months
Mr John O'Callaghan, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
This was a pilot study of some interest. It was powered for a significance level of 0.10, with 2:1 randomisation given the cost of the study drug (eculizumab). Only 16 patients were included in the study, over an enrollment period of 3 and a half years. Treatment with eculizumab was associated with stabilization of renal function compared to no treatment
in patients with de novo DSA. The study is limited by its size and the variability in the trajectory of renal function of the included patients. It is too small to really comment on the impact of the study drug on safety outcomes, such as infection rates.
Associate Professor John Kanellis, Department of Nephrology, Monash Health and Centre for Inflammatory Diseases, Department of Medicine, Monash University. Clayton, Melbourne, Australia
Conflicts of interest:Our centre has participated in trials using eculizumab sponsored by Alexion Pharmaceuticals
This study examined the use of eculizumab to treat chronic antibody-mediated rejection in renal transplant recipients in the presence of de-novo DSA. The findings suggest a possible role for eculizumab in stabilizing allograft function. The study was small and the benefit was evident in the last two months of treatment (months 5-6). Prior to that, no difference could be discerned.
A longer treatment duration may have revealed greater separation of the groups and may have demonstrated greater clinical significance. Given the slow rate of deterioration in this condition (eGFR loss of 3.63ml/min/year) the control group showed little change in eGFR over 6 months. The treatment group were slightly more stable however the clinical difference between groups is minor and it is hard to draw conclusions from this short duration of treatment. Additionally, the study was unable to demonstrate a difference in endothelial cell associated transcript (ENDAT) expression between the groups. Again, a longer duration of treatment may have been necessary to show a difference in this chronic disease process. Further studies with a longer treatment period and with greater subject numbers would need to be performed in order to further determine the benefit of this treatment approach.
We hypothesize that de novo donor specific antibody (DSA) causes complement-dependent endothelial cell injury in kidney transplants, assessed by expression of endothelial cell associated transcripts (ENDATs), which may be attenuated through complement inhibition. Fifteen subjects (5 control: 10 treatment) with DSA and deteriorating renal function were enrolled. Treatment group received 6-months of eculizumab followed by 6-month's of observation, while controls were observed. Primary endpoint was percent change in eGFR trajectory over treatment period. Treatment group had improved eGFR trajectory versus control, based on our predetermined two-sided 0.10 significance level (p=0.09). Within-subject analysis of treatment subjects between 6-month intervals did not show significant change (P=0.60). Modeling C1q status showed that C1q positive patients had significantly higher mean eGFR than patients who had negative C1q (p=0.04). Biopsies revealed elevated renal ENDATs in most subjects, but these were not reduced with complement inhibition. Our data suggest that eculizumab treatment may stabilize kidney function in patients with chronic-persistent DSA based on our pilot a priori significance threshold. ENDAT expression predicative of acute humoral injury are not reduced with complement inhibition in this chronic setting. Further studies will be necessary to discriminate which patients may benefit from eculizumab. This article is protected by copyright. All rights reserved.
Harrison, J. J., Badr, S., Hamandi, B., Kim, S. J.
Transplantation. 2016;[record in progress]
Aims:To evaluate the impact of a home delivered computer-based education (CBE) program on medication knowledge, satisfaction and immunosuppressant adherence in de novo solid organ transplant recipients (SOTR).
Interventions:Participants were randomised to receive either the standard of care (control group), or the standard of care plus the Transplant Medication Information Teaching Tool (TMITT) as an online CBE program (intervention group).
Outcomes:The primary outcomes measured were change in knowledge and satisfaction. The secondary measured outcome was adherence to the immunosuppressive regimen.
Follow Up:3 months
Centre for Evidence in Transplantation
De novo solid organ transplant recipients who had received standard, in-hospital, pharmacy-led self-medication teaching were randomised to receive additional computer-based education or no additional education. Power calculations showed that 110 patients per study arm were needed. The study randomised 246 patients using concealed allocation and 209 patients were included in the 3-month analysis. There were no differences between groups at
3 months in terms of medication knowledge, satisfaction with the medication information provided and medication adherence indicating that the computer-based education did not provide additional value to the standard, in-hospital self-medication programme alone.
Ms Teresa Shafer, Progress in Transplantation, Fort Worth, TX, USA
Knowledge and administration of medications is central to post-transplant outcomes. Post-transplant education to ensure mastery of such knowledge in order to maintain the graft has always been a part of patient treatment and a bane to transplant professionals so charged with the task. The article by Harrison and colleagues measures the efficacy of a computer based education (CBE) at
home against the standard in-clinic/office setting by the practitioner. Randomized solid organ transplant recipients at this single center trial were sorted into a standard educational arm and an intervention arm that added CBE in the home. The study found no difference in outcomes between the control or standard group and the intervention group receiving CBE. While the study identified no silver bullets to the current labor intensive and costly provision of such education by skilled transplant practitioners in the standard setting, it served a valuable purpose in providing the first RCT evaluation of such an intervention. The study reinforces the reality that transplantation is highly specialized, hands-on and dependent on heavy involvement of skilled practitioners not only in the operating room but in the post-transplant phase when maintenance of the graft assumes center stage. There appear to be no shortcuts here and we benefit from their well-designed study to say so.
BACKGROUND De novo solid organ transplant recipients (SOTR) have a steep learning curve to acquire medication knowledge. Without adequate knowledge, SOTR are at risk of nonadherence and poor transplant outcomes. METHODS In this nonblinded, randomized controlled trial, de novo SOTR received standard teaching with or without postdischarge computer-based education (CBE) at home. Primary outcomes were change in knowledge (quiz and recall) and satisfaction, assessed by questionnaires at baseline and 3 months. Adherence was evaluated via self-report and immunosuppressant levels. RESULTS Two hundred forty-six patients were randomized and 209 completed the 3-month analysis. In the intervention arm, 73 (57.9%) used the CBE program. Change in knowledge quiz score did not differ between groups (4.9% vs 0.6%; P = 0.084), despite a significant increase within the intervention (72.4% vs 77.3%, P = 0.007) but not the control (76.0% vs 76.6%, P = 0.726) arms. Both groups had a significant improvement in recall (intervention, 56.7% vs 82.1%, P < 0.001; control, 51.3% vs 79.7%, P < 0.001), with similar changes in scores (25.4% vs 28.4%, P = 0.55). Change in satisfaction differed between groups (intervention, 1.2% vs control, -4.9%; P = 0.050). There was a significant decline in satisfaction within the control group (88.4% vs 83.5%, P = 0.035), whereas satisfaction was maintained with the intervention (85.6% vs 86.8%, P = 0.55). Adherence was similar in both groups. CONCLUSIONS Knowledge improved over the study period in both groups, with no incremental benefit for the intervention. Patient satisfaction was maintained with the CBE program. More research is needed to identify barriers to uptake of CBE at home and to develop effective strategies for posttransplant education.