2018 American Transplant Congress, June 2-6, Seattle, WA United States of America

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Methods This is a report of pilot, prospective, single center, open label, randomized study of the efficiency and safety of MSC induction of immunosupression over standard IIT in regard of immunological dysfunction development and kidney transplant function improvement. Inclusion criteria: adult kidney transplant recipients who received first kidney transplant. Exclusion criteria were high immunological risks at the time of surgery (HLA mismatching, PRA>0%). In the first group MSCs introduction was performed on 0 and 4 days after surgery in total dose of 4 million cells/kg in 2 infusions (2 million cells/kg at a time). In the second group patients received basiximab 20 mg on 0 and 4 days after transplantation. Third group hadn’t any induction therapy. Maintenance therapy includes calcineurine inhibitor, mycophenolic acid, steroids and didn’t differ among groups. The protocol kidney transplant biopsies were performed on the 7th day after surgery. Results of our research showed that the frequency of graft dysfunction which was associated with rejection, was approximately identical among groups – 40%. At the same time the severity of acute rejection was rather low according to the results of biopsies in the MSC group. The level of serum creatinin decreased more intensively in 2nd group (baziliximab) and was assessed as 265±125 μmol/l at the 7 day after operation. In the 1st (MSC) and 3rd groups it was respectively 313±201 μmol/l and 548±317 μmol/l (p>0,05). Dynamics of GRF level restoration didn’t differ in groups and reached 31,72±10,34 ml/min, 34,7±12,4 ml/min, 35,7±11,97 ml/min respectively on 7 day after transplantation. We didn’t observe any significant difference in frequency and strength of side effects in study groups. Conclusion Application of allogeneic MSC as induction immunosupressive therapy in kidney transplantation is effective and safely. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Introduction Steroids represent one of the mainstays of immunosuppression after kidney transplant (KT). Steroid withdrawal reduces metabolic and cardiovascular complications, but whether it increases the risk of acute rejection and the generation of donor-specific anti-HLA antibodies (DSA) is currently undetermined. Materials and Methods In a controlled clinical trial (NCT02284464), a total of 176 KT patients with low immunological risk were recruited to randomly receive either conventional triple immunosuppression: steroids, TAC and MMF versus steroid withdrawal at the third post-KT month. We compared the incidence of de novo DSA, determined by Luminex Mixed and Luminex Single Antigen (One Lambda®), and its impact on graft histology in patients with steroid withdrawal at the 3 post-KT month (after a protocol biopsy) versus patients who continue to receive conventional triple immunosuppression. Results So far, 68 patients have been randomized (34 per group), with no significant differences in the clinical and demographic characteristics between the groups. The intermediate analysis in those patients who had completed one year of follow-up (n=28) showed no significant differences in the formation of DSA (0% vs. 0%), nor was there rejection in those patients in whom prednisone was withdrawn after randomization. Patients with triple therapy showed a trend toward better renal function compared to those without steroids at the first post-KT year (1.29±0.25 vs. 1.56±0.42 mg/dL, P=0.088). HbA1c levels were similar between both group at the first post-KT year (5.79±0.59 vs. 5.68±0.81%, P=0.734). Conclusion The preliminary results show that steroid withdrawal at the 3 month post-KT seems safe when assessing the appearance of rejection and formation of DSA compared to the patients who continued to receive conventional triple immunosuppression. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional–FEDER, RETICS (REDINREN RD12/0021/0015, RD16/0009/0006, RD16/0009/0003, RD16/0009/0030, RD16/0009/0031). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Despite the allograft-risk associated with DSA, the development of post-transplant HLA donor-specific antibody (DSA) is not well described in liver transplant (LT) patients undergoing immunosuppression (IS) minimization and IS withdrawal. We analyzed the post-transplant DSA development, defined as the development of de novo DSA (dnDSA) or the rebound of pre-transplant DSA or both, in: 69 LT patients, enrolled in the A-WISH trial, who received calcineurin inhibitors monotherapy; and of which 40 stable patients who were randomized to IS maintenance (n=9) or IS withdrawal (n=31). Among the latter, 9 tolerant patients were off IS completely. All DSA were screened using Luminex Single antigen beads with a 1000 MFI cutoff for positivity. Among the patients who achieved stable IS monotherapy (Figure A), the incidence of post-transplant DSA, dnDSA and pre-transplant DSA rebound was 28%, 19% and 9%, respectively. The incidence of dnDSA was higher in non-randomized patients (p=0.002). The majority of dnDSA was HLA-DQ DSA. Last, early acute rejection was associated with an increased risk of developing dnDSA (HR=13.5, 95%CI[4.03-45.22]). Among the stable randomized patients (Figure B), the incidence of post-transplant DSA was 65%, dnDSA was 60%, and pre-transplant DSA rebound was 13%. The incidence of dnDSA between the IS maintenance, tolerant and non-tolerant patients was similar. The majority of dnDSA was HLA-DQ DSA. Lastly, post-transplant DSA was found to be a risk factor for graft rejection during IS withdrawal (HR=6.99, 95%CI[2.64-18.54]). JOURNAL/trans/04.02/00007890-201807001-00325/figure1-325/v/2018-08-28T120805Z/r/image-tiff In conclusion, the development of post-transplant DSA increases after an episode of early acute rejection, after early minimization of IS, and after complete withdrawal of IS. It is yet to be explored whether early expression of DSA in the setting of low or no IS is associated with long term impact on the allograft. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Inflammation plays an important role in causing complications in CKD and transplant patients. C-reactive protein and pro-inflammatory cytokines could predict outcomes in transplant patient. Poor oral health results in inflammation and cytokine production. There is need to evaluate the benefit of good oral hygiene on renal transplant outcome. A randomized controlled trial was carried out amongst CKD patients going for renal transplantation. The randomization was done in 100 CKD patients going for transplantation. All patients had dental and oral examination (Type III clinical examination as per American Dental Association specifications and WHO oral health proforma, 2013) Group I (Non interventional group) 50 patients. Group II (Intervention group) - 50 patients of chronic kidney disease going for transplantation. Group III (Control group) comprised of 50 healthy age, sex matched subjects. Intervention group followed regular tooth brushing, use of dental floss along with use of mouth wash twice every day and counseling sessions for good oral and dental care for a period of 3 months after transplant. Non-intervention group continued usual oral and dental care. Both groups had base line oral examination just before transplantation and at 3 months after transplant. The oral and dental findings specially the periodontitis score was compared between groups I and II and with the healthy controls. CRP (C- reactive protein) values were assayed at baseline and after 3 months. Comparison of CRP values between Interventional and non-interventional groups at baseline and at 3months showed that periodontitis score and CRP significantly came down at 3 months in intervention group as compared to non- intervention group . CRP values in the interventional and non-intervention groups were analyzed in relation to presence of donor specific antibodies (DSA) and HLA mismatch scores in the two groups. Our data shows that after aggressive dental and mouth hygiene routine, intervention group patients showed significant decline in CRP values as compared to the non intervention group. It almost reached close to values in normal controls. This was seen in both patient groups with less than and more than 3-HLA mis-matches. In patients with DSA at time of transplantation, base line CRP values were significantly higher as compared to those with no DSA, but CRP values even in DSA positive group came down significantly with aggressive dental and mouth care routine at 3 months after transplantation JOURNAL/trans/04.02/00007890-201807001-00259/figure1-259/v/2018-08-28T120805Z/r/image-tiff This is a report of results of a randomized control study in transplant recipients showing the benefits of good oral and dental care in relation to inflammation, DSA and HLA mis-matches. The present study concludes that the oral hygiene of the patients with chronic kidney disease going for transplant is deteriorated. Good oral and dental care in transplant recipients can improve inflammation which could have beneficial effect on post transplant outcomes. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

18th Congress of the European Society for Organ Transplantation, 24-27 September 2017, Barcelona, Spain

Bootcongres, Dutch Transplantation Society, 8-9 March 2017, Zeist, The Netherlands

2017 American Transplant Congress, April 29 - May 3, Chicago, United States of America.

18th Congress of the European Society for Organ Transplantation, 24-27 September 2017, Barcelona, Spain