scholarly journals 87. Heart and Lung Transplants From HCV-Viremic Donors to Uninfected Patients: Longer-Term Follow-Up

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S5-S5
Author(s):  
Ann E Woolley ◽  
Hilary J Goldberg ◽  
Steve K Singh ◽  
Mandeep R Mehra ◽  
Michael M Givertz ◽  
...  
Keyword(s):  
Graft Survival ◽  
Antiviral Treatment ◽  
Graft Function ◽  
Transplant Recipients ◽  
Heart Transplants ◽  
Post Transplant ◽  
Lung Transplants ◽  
Grade 3 ◽  
Direct Acting

Abstract Background The DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct-acting antivirals (DAA). The 6-month results from that study of 35 patients are encouraging, but longer-term data from a larger cohort are needed to better define the risk–benefit profile. Methods We conducted a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was pre-emptively administered for 4 weeks, beginning within hours of transplant. The primary outcome was a composite of HCV clearance and graft survival at 6 months post-transplant. Secondary outcomes included graft survival and mortality at 12 months and the occurrence of grade 3 or higher adverse events (AEs). This protocol is IRB approved and all participants provided written informed consent (NCT03086044). Results Between March 2017 and March 2019, 57 participants were enrolled: 46 received lung and 11 received heart transplants. The median donor HCV viral load (VL) was 889,817 IU/mL (IQR 212,062–4,641,078). Of the 57 recipients, 53 (93%) had detectable HCV VL immediately after transplant, with median VL of 1,460 IU/mL (IQR 463–6,618). HCV VL became negative by about 2 weeks and subsequently remained undetectable in all participants. Forty-nine of 49 (100%) and 34 of 35 (97%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months and 1-year post-transplant, respectively. No treatment-related serious AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections. Conclusion In patients who received thoracic organs from HCV viremic donors, a 4-week antiviral treatment course initiated within hours of transplant prevented the establishment of HCV infection. These data demonstrate that thoracic organs from HCV viremic donors can be transplanted safely with excellent graft and recipient survival at 12 months with a similar AE profile compared with transplant recipients who received thoracic organs from non-HCV donors. Two-year outcomes will be available in October 2019. Disclosures All Authors: No reported Disclosures.

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Clara Pardinhas ◽  
Rita Leal ◽  
Francisco Caramelo ◽  
Teofilo Yan ◽  
Carolina Figueiredo ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Graft Function ◽  
Delayed Graft Function ◽  
First Year ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p<0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p<0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p<0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p<0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p<0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

scholarly journals Indicators of monocyte-derived component of the immune system in patients with satisfactory renal graft function

2020 ◽  
Vol 22 (2) ◽  
pp. 53-62
Author(s):  
S. V. Zybleva ◽  
S. L. Zyblev
Keyword(s):  
Kidney Transplant ◽  
Negative Correlation ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Long Term Follow Up

Objective: to study the indicators of the monocyte-derived component of the immune system in kidney transplant recipients with satisfactory early and delayed renal transplant function. Materials and methods. The study involved 76 kidney transplant recipients. Concentrations of serum creatinine (sCr), serum urea (sUr) and serum cystatin C (sCysC) were measured. CD14+mid/high and CD14+low were isolated from CD14+ monocytes. CD64- and CD86-expressing cell counts were determined for each subpopulation. Immunological examination was performed before surgery, as well as at days 1, 3, 7, 30, 90, 180 and 360 after surgery. Results. There was significant imbalance between the two monocyte subpopulations before transplantation and in the early post-transplant period (first 3 months). By the end of a 6-month follow-up period, the percentage of CD14+ cells had normalized. The dynamics of the subclasses of CD86-expressing monocytes in the post-transplant period is somewhat different from the dynamics of the total count for these monocytes. However, by the end of a 6-month follow-up period, these biomarkers returned to normal for the group of healthy individuals (CD14+mid/highCD86+ p180 = 0.079; CD14+lowCD86+ p180 = 0.789). CD14+lowCD64+ level was significantly higher in the kidney transplant group than in the control group during the entire follow-up period (p0 = 0.0006, p1 = 0.0001, p7 = 0.005, p30 = 0.005, p90 = 0.007, p180 = 0.0002, p360 = 0.001). On the other hand, CD14+mid/highCD64+ count for up to 180 days was not significantly different from that of the control group (p0 = 0.561, p1 = 0.632, p7 = 0.874, p30 = 0.926, p90 = 0.912), with subsequent significant increase by day 360 of follow-up (p180 = 0.01, p360 = 0.003). We observed a negative correlation between CD14+lowCD86+ level at day 0 and sCr levels at day 7 (r = –0.4; p = 0.008) and day 360 (r = –0.34; p = 0.042) and sCysC level at day 7 (r = –0.57; p = 0.014). A negative correlation was also found between CD14+lowCD86+ at day 1 and sCr levels at day 7 (r = –0.4; p = 0.005) and day 360 (r = –0.39; p = 0.02). There was positive correlation between the CD14+lowCD64+ subpopulation index at day 0 and sCr (r = 0.54; p = 0.008) and sCysC (r = 0.6; p = 0.008) levels at day 7, and also between the CD14+lowCD64+ count at day 1 and sCr (r = 0.55; p < 0.0001) and sCysC (r = 0.58; p = 0.004) levels at day 7. CD14+mid/highCD64+ at day 0 negatively correlated with sCysC level at day 360 (r = –0.85; p = 0.015), while CD14+mid/highCD64+ at day 7 positively correlated with sCysC level at day 360 (r = 0.50; p = 0.016). Conclusion. Before transplant surgery, CD14+mid/high, CD14+mid/highCD86+ , and CD14+lowCD86+ counts were reduced, while those of CD14+low, CD14+mid/highCD64+ and CD14+lowCD64+ were increased. By the 6-month follow-up, all these subpopulations except CD14+mid/highCD64+ had reached values for healthy people. Positive correlation between CD14+mid/high, CD14+lowCD64+ , CD14+mid/highCD86+ , CD14+mid/highCD64+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up, as well as negative correlation between CD14+low, CD14+lowCD86+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up can serve as a predictor of renal graft function.

scholarly journals 980. Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S581-S581
Author(s):  
Clover N Truong ◽  
Michael D Nailor ◽  
Rajat Walia ◽  
Lauren Cherrier ◽  
Aasya Nasar ◽  
...  
Keyword(s):  
Lung Transplant ◽  
Endemic Area ◽  
High Risk Patient ◽  
Antifungal Prophylaxis ◽  
Definitive Treatment ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Lung Transplants ◽  
Lung Transplant Recipients

Abstract Background Previous studies suggested that 6-12 months of universal or targeted azole prophylaxis is effective in preventing coccidioidomycosis for various organ transplant recipients. However, limited reports have described outcomes with longer prophylactic durations or using mold-active azoles in lung transplant recipients. Therefore, the purpose of this study was to investigate the incidence of coccidioidomycosis and tolerability of universal lifelong azole therapy in this high-risk patient population. Methods This study was an IRB-approved, retrospective cohort study of lung transplant recipients transplanted from January 2013 through December 2018. Adult recipients who were initiated on azole antifungal prophylaxis were eligible for inclusion. Recipients who died or received pre-emptive or definitive treatment for coccidioidomycosis during the transplant admission, or who received a previous transplant were excluded from the study. Outcomes were assessed through December 2019 or until the time of coccidioidomycosis diagnosis, death, second transplant, or date lost to follow-up. Results Of 544 lung transplants completed between 2013-2018, 493 patients were included with a mean age at transplant of 62 ± 11; 57.3% were male, 88.6% were white, and 77.1% developed post-transplant diabetes. The majority of patients ( &gt; 70%) lived in Arizona or California pre-transplant and at 1-year post-transplant, and most patients had primary transplant indication of COPD and/or pulmonary fibrosis (~75%). One proven coccidioidomycosis infection and one new asymptomatic seropositivity for Coccidioides (incidence 0.2% each) occurred during the study period with median follow-up duration of 31 months. Azole therapy changes were common but permanent discontinuation was rare (1.4%) with reasons for azole switch varying among the different agents as summarized in Table 1. Table 1. Comparison of azole antifungal exposures and reasons for discontinuation Conclusion Lifelong azole antifungal prophylaxis was well-tolerated and effectively protected lung transplant recipients at an Arizona transplant center against coccidioidomycosis. Thus, in the absence of documented intolerance or contraindication, universal lifelong azole antifungal prophylaxis should be considered for all lung transplant recipients residing in a coccidioidomycosis-endemic area. Disclosures Michael D. Nailor, PharmD, BCPS (AQ-ID), AbbVie (Consultant)Merck (Consultant)Shionogi (Consultant) Rajat Walia, MD, Astellas (Consultant, Speaker)

Outcome of Heart Transplants 15 to 20 Years Ago: Graft Survival, Post-transplant Morbidity, and Risk Factors for Mortality

2008 ◽  
Vol 27 (5) ◽  
pp. 486-493 ◽  
Author(s):  
Jean C. Roussel ◽  
Olivier Baron ◽  
Christian Périgaud ◽  
Philippe Bizouarn ◽  
Sabine Pattier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Survival ◽  
Heart Transplants ◽  
Post Transplant

scholarly journals Associations of pre-transplant anemia management with post-transplant delayed graft function in kidney transplant recipients

2012 ◽  
Vol 26 (5) ◽  
pp. 782-791 ◽  
Author(s):  
Miklos Z. Molnar ◽  
Csaba P. Kovesdy ◽  
Laszlo Rosivall ◽  
Suphamai Bunnapradist ◽  
Junichi Hoshino ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Anemia Management

Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ceren Atasoy Tahtasakal ◽  
Ahsen Oncul ◽  
Dilek Yildiz Sevgi ◽  
Duygu Demirbas ◽  
Alper Gunduz ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Direct Acting Antiviral ◽  
Direct Acting

scholarly journals A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

2021 ◽  
Vol 7 ◽  
Author(s):  
Rainer Oberbauer ◽  
Matthias Edinger ◽  
Gabriela Berlakovich ◽  
Peter Kalhs ◽  
Nina Worel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kidney Transplant ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Donor Bone Marrow ◽  
Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR &lt;35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

scholarly journals P1762THE EFFECT OF IMMUNOSUPPRESSIVE THERAPY ON THE CLINICAL FOLLOW-UP OF BK VIRUS IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gulay Yilmaz ◽  
Volkan Polatkan ◽  
Ebru Ozdemir ◽  
Turker Erturk ◽  
Emel Tatli ◽  
...  
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Antiviral Treatment ◽  
Immunosuppressive Treatment ◽  
Bk Virus ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Group I ◽  
The Mean

Abstract Background and Aims BK virus nephropathy occurs in up to 10% of kidney transplant recipients and can result in graft loss. The reactivation of BK virus is largely asymptomatic, and routine surveillance especially in the first 12-24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and antiviral treatment in the early stages may be effective in stopping BK virus replication. This study is designed to investigate the effect of management in immunosuppressive therapy on BK virus titers and graft functions in our kidney transplant group. Method A total of 370 kidney transplant recipients between the ages of 18-69 years and receiving a triple immunosuppressive therapy (Tacrolimus+Mycophenoloic Acid+Prednisolone) were included in the study. Demographic characteristics, BK virus titers, serum creatinine and immunosuppressive drug (Tacrolimus, Everolimus) levels were measured at regular intervals in the first 24 months. Among these patients 43 of them were found to have BK virus positivity. At the time of the detection of BK virus positivity, patients were divided into three groups regarding the change in the immunosuppressive protocols: Group I: Tacrolimus + Everolimus + Prednisolone, Group II: Everolimus + Prednisolone, Group III: Tacrolimus + Prednisolone. BK virus titers and graft functions of all three groups were compared with each other. SPSS 15 for Windows was used for statistical analysis. Results The mean age of the patients was 45.3 years, and the mean duration of transplantation was 16.3 months at the time of the BK virus positivity. During the follow-up, mean Tacrolimus levels were found to be in their highest value (14.1 ng/mL) in the posttransplant three months while BK virus titer reached the highest value (1.1x106 copies/ml) in the posttransplant seven to nine months. Increased creatinine values two months after BK virus positivity were strongly correlated (p = 0.02, p = 0.008, p = 0.05, p = 0.002 at 6th, 9th, 12th and 24th months, respectively). A significant decrease in BK virus titers was observed in all three groups due to reductions in immunosuppressive treatment protocol (p = 0.005, p = 0.003, p = 0.028, in groups I, II, III respectively). Conclusion Our study favors the benefits of the prospective screening for BK virus to identify early viral replication, permit intervention, and prevent progression to nephropathy or allograft loss. The best studied treatment for BK viremia and nephropathy is careful reduction of immunosuppression

scholarly journals High Plasma Branched-Chain Amino Acids Are Associated with Higher Risk of Post-Transplant Diabetes Mellitus in Renal Transplant Recipients

2020 ◽  
Vol 9 (2) ◽  
pp. 511 ◽  
Author(s):  
Maryse C. J. Osté ◽  
Jose L. Flores-Guerrero ◽  
Eke G. Gruppen ◽  
Lyanne M. Kieneker ◽  
Margery A. Connelly ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Amino Acids ◽  
Renal Transplant ◽  
Branched Chain Amino Acids ◽  
Resonance Spectroscopy ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Branched Chain

Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a functioning graft for ≥1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 ± 13.6 y (53.6% men) and plasma BCAA was 377.6 ± 82.5 µM. During median follow-up of 5.3 (IQR, 4.2–6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08–1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c < 5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM.

Sign in / Sign up

Export Citation Format

Share Document