American Transplant Congress, 30 May- 3 June 2020, Pennsylvania, USA

16th World Congress on Public Health 2020, 12-16 October 2020

American Transplant Congress, 30 May- 3 June 2020, Pennsylvania, USA

American Transplant Congress, 30 May- 3 June 2020, Pennsylvania, USA

19th Congress of the European Society for Organ Transplantation, 15-19 September 2019, Copenhagen, Denmark

19th Congress of the European Society for Organ Transplantation, 15-19 September 2019, Copenhagen, Denmark

19th Congress of the European Society for Organ Transplantation, 15-19 September 2019, Copenhagen, Denmark

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Background Patients with type 1 diabetes (T1D), treated with simultaneous pancreas and kidney transplantation (SPK), commonly have advanced stages of diabetic retinopathy (DR). New therapeutic agents targeting the production of proangiogenic signalling pathways in the in retina have been tested in experiments, including local mTOR inhibitors application. We initiated a randomized clinical trial to evaluate the role of systemic mTOR inhibition after SPK in the course of DR. Methods Main objective is a complex ophthalmological endpoint (grade and progression of the DR, new indication to laser therapy, clinically significant macular edema, visual acuity, cataract grade, central macular thickness, intravitreal bleeding and neovascularisation). Secondary endpoints are patient and graft survival, graft function, wound healing and complications. We include patients with T1D on the waiting list for SPK and randomize them to treatment with natrium mycophenolate (1440 mg/day) or everolimus (through concentration 4–8 ng/l). All receive tacrolimus, induction with antithymocyte globulin and short-term steroid treatment. Complete eye examination including optical coherence tomography is done at baseline, 6, 12 and 24 months post-transplant. We performed an updated analysis of our data for secondary endpoints. Results After three years 47 patients (out of 50 enrolled) have undergone successful SPK, 14 have successfully completed the 2 years, 25 have completed 1 year follow up. Our data show comparable patient and graft survival and long term kidney function. There was a higher incidence of biopsy proven kidney graft rejections (mostly in the cathegory of borderline changes) and pancreas graft rejections, but neither of them statistically significant, in the group treated with everolimus. We also observed significantly higher glycated haemoglobin levels in the everolimus-treated group, however with slightly higher levels of both fasting and stimulated C-peptide throughout all the follow-up period. In the early postoperative period, the rate of serious complications with need for surgical revision and the time to wound healing did not differ between the two groups. Nevertheless, in the longer follow up, significantly higher number of subjects in the everolimus-treated group developed hernias requring surgical treatment. In the mycophenolate-treated group we have seen higher incidence of severe leucopenias and neutropenias and recurring urinary tract infections. Other complications (i.e. tremor, diabetic foot ulcers, viral infections, diarrhoea, progression of ischaemic heart disease, rash and others) did not differ significantly between the compared groups. Conclusion Assessment of the preliminary data for secondary endpoints shows results in accordance with previous findings. Ophthalmological endpoints will be evaluated when sufficient amount of data allows a valid statistical analysis. Study is open for new participants. Ministry of Health of the Czech Republic, grant number 15–26746 A. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. NIH CTOT 15. Introduction Simultaneous pancreas-kidney transplants (SPK) are dependent on calcineurin inhibitors (CNI) to block the alloimmune and recurrent autoimmune response following transplant. Ironically, CNIs are diabetogenic and toxic to the kidney, negatively impacting long-term allograft function. The NIH multicenter CTOT-15 study tested the hypothesis that thymoglobulin induction and co-stimulation blockade with belatacept (bela) could minimize and eliminate CNI and steroids following SPK. Methods Primary SPK recipients were randomized to control or investigational arms as outlined in Figure 1. SPK recipients randomized to the investigational arm were eligible for CNI withdrawal at 40 weeks provided they had stable kidney and pancreas function, had no evidence of cellular and antibody mediated rejection during the first 280 days, and had no evidence of DSA at week 36 following SPK. Primary endpoint was estimated glomerular filtration rate (eGFR) at 52 weeks. Selected secondary endpoints included the incidence and severity of rejection, rates of insulin independence, HgbA1C, and safety measures. Autoantibody titers associated with Type I diabetes were tested at the time of transplant and monitored throughout the trial and at the time of CNI withdrawal. Pre-transplant frequency of CD4 57hi/PD1lo, a potential marker for ability to withdraw CNI, was measured at baseline in both groups. Results Twenty-one patients were randomized to the control arm; 22 to the investigational arm (Figure 1). 15/22 SPK recipients in the investigational arm were eligible for CNI withdrawal, and 11 completed withdrawal. SAE’s were common in both arms (Table 1). Renal function was equivalent in both groups. The high rate of pancreas AR following CNI withdrawal promoted the DSMB to stop CNI withdrawal. Autoantibody positivity at time of transplant for the entire cohort was 39.5% GAD65, 14.0% IA2, 72.1% MIAA and 14.0% ZNT8RW (Table 1). Although no general association between antiGAD65 titers and rejection events were detected in this cohort, there was a marked increase observed at the time of CNI withdrawal and rejection in one participant. No statistical difference was observed between pre-transplant frequencies of CD4 57hi/PD1lo T cells in rejectors versus non-rejectors. JOURNAL/trans/04.02/00007890-201807001-00382/figure1-382/v/2018-08-28T120805Z/r/image-tiff JOURNAL/trans/04.02/00007890-201807001-00382/figure2-382/v/2018-08-28T120805Z/r/image-tiff Conclusions