scholarly journals P1701ANTIBODY MEDIATED REJECTION: CLINICAL PHENOTYPE MATTERS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carla Burballa Tarrega ◽  
Laura Llinás ◽  
Anna Buxeda ◽  
Carlos Arias Cabrales ◽  
María José Pérez Sáez ◽  
...  
Keyword(s):  
Graft Survival ◽  
Clinical Phenotype ◽  
Specific Treatment ◽  
Clinical Group ◽  
Histologic Diagnosis ◽  
Protocol Biopsy ◽  
Antibody Mediated Rejection ◽  
Increased Risk ◽  
Protocol Biopsies ◽  
Isolated Proteinuria

Abstract Background and Aims Protocol biopsies following kidney transplantation (KT) allow the histological diagnosis of antibody-mediated rejection (ABMR) with stable renal function (RF). Controversy arises when considering isolated proteinuria as a clinical biomarker. Currently, there is no effective treatment for ABMR and transplant units may decide on treatment independently of the clinical expression. Method KT recipients (1987-2017) with post-KT biopsies (2008-2018) showing ABMR graft lesions (category 2-Banff’2015) >1year post-KT were included. Cases were grouped into phenotypes of ABMR according to the clinical picture at biopsy : 1) acute RF impairment (↑creatinine >15% three weeks before biopsy) with/without proteinuria and with/without DSA detection. 2) sub-acute RF impairment (↑creatinine >15% six months before biopsy) with/without proteinuria and with/without DSA detection, 3) performed for DSA detection with stable RF and no proteinuria or 4) protocol biopsy, with stable RF, no proteinuria or DSA detection. We considered an additional category: 5) isolated proteinuria (↑>500 mg or x2 six months before biopsy). Categories 1), 2) and 5) were considered clinical ABMR. Categories 3) and 4) were considered subclinical ABMR. We aimed to evaluate graft outcomes in the different ABMR phenotypes. Results In a cohort of 105 KT recipients with histologic lesions of ABMR, biopsies corresponded to phenotypes 1) in 35 (33%), 2) 10 (9,5%), 3) 21 (20,3%), 4) 14 (13,4%) and y 5) in 25 23,8%). No differences between clinical and subclinical ABMR were found in baseline characteristics except for donors ‘age, who were older within the clinical group (51.8±18.8 vs. 43.88 ±16.1; p=0.04). At time of biopsy, subclinical had better RF than clinical ABMR (creatinine 1.3±0.4 mg/dl vs. 2.2±1.1 mg/dl; p=0.02) and less proteinuria (161 mg/g [IQR 93-269] vs 939 mg/g [IQR 412-2000]; p=0.001) Graft survival was worse in those patients with acute and sub-acute RF impairment, followed by those with isolated proteinuria (Figure 1). In comparison to subclinical ABMR, those with RF impairment and isolated proteinuria had an increased risk of graft lost; HR 9.4 (95% IC 2.2-40.7, p=0.002) and 4.8 (95% IC 1.01-23.2, P=0.05) respectively. DSA detection in these groups did not impact graft survival. Specific treatment was not different among groups, except for steroid pulses, which were more frequently applied in cases of ABMR with clinical manifestation. Conclusion The clinical phenotypes of ABMR influence long-term graft survival independently from treatment. Understanding graft evolution according to clinical phenotype at the time of histologic diagnosis should guide the therapeutic strategy, to balance risk-benefit ratio.

scholarly journals P1738COULD ADDING BORTEZOMIB HAVE BENEFIT FOR ANTIBODY MEDIATED REJECTION AFTER KIDNEY TRANSPLANTATION?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nooshin Dalili ◽  
Mohsen Nafar
Keyword(s):  
Kidney Transplantation ◽  
Intravenous Immunoglobulin ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Vascular Inflammation ◽  
Standard Of Care ◽  
Kidney Transplant Recipients ◽  
Standard Regimen ◽  
Antibody Mediated Rejection ◽  
Protocol Biopsies

Abstract Background and Aims Antibody Mediated Rejection (ABMR) is a severe complication that frequently occurs after kidney transplantation. The present RCT designed to evaluate the role of adding Bortezomib to standard regimen with plasma exchange, intravenous immunoglobulin and Rituximab in treatment of AMR after kidney transplantation. Method 26 kidney transplant recipients (KTRs) with a biopsy proven diagnosis of AMR and positive DSA in a randomized clinical trial were compared: Thirteen KTRs treated with plasmapheresis, intravenous immunoglobulin and rituximab (PE-IVIG- RTX ) plus bortezomib versus 13 patients treated with standard of care regimen without bortezomib. We evaluated graft survival and DSA titer with MFI during a year after biopsy proven diagnosis. Results Statistical difference in graft survival between the two groups was noted: three out of 13 patients in the PE-IVIG-RTX group (23%) and 1/13 in the bortezomib group (7.5%) experienced loss of allograft function at a median time after diagnosis of 6 month and 12 month, respectively. DSA MFI titers 12 month after AMR diagnosis showed significant reducing slope in Bortezomib group. Regarding pathological changes micro vascular inflammation (glomerulitis + peritubular capillaritis score) reduced after PE-IVIG- RTX plus bortezomib in 7 out of 13 patients whom underwent protocol biopsies after treatment (53%) (Median score 3 in pre- treatment biopsy vs. 1 in post-treatment biopsy; P = 0.036). Conclusion Although DSA titer may not differ at 6 months after treatment of AMR between those who received standard regimen and those treated with adding Bortezomib, but at the end of one year patients treated with standard regimen plus Bortezomib reached lower MFI DSA titer. Adding Bortezomib to PE-IVIG- RTX for the treatment of AMR after kidney transplantation may enable clinicians to fight the DSA better and change the future of next generation of highly sensitized kidney transplant candidates.

scholarly journals Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation

2019 ◽  
Vol 14 (7) ◽  
pp. 1056-1066 ◽  
Author(s):  
Malte Ziemann ◽  
Wolfgang Altermann ◽  
Katharina Angert ◽  
Wolfgang Arns ◽  
Anette Bachmann ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Living Donation ◽  
Hla Antibodies ◽  
Transplant Survival ◽  
Antibody Mediated Rejection ◽  
Increased Risk

Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

MO926RAPID VS. LATE RE-TRANSPLANTATION FOR EARLY KIDNEY GRAFT LOSS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Diana Rodríguez Espinosa ◽  
Jose Jesus Broseta Monzo ◽  
Evelyn Hermida-Lama ◽  
Elena Cuadrado ◽  
Jimena Del Risco ◽  
...  
Keyword(s):  
Graft Survival ◽  
Graft Failure ◽  
Patient Survival ◽  
Statistical Significance ◽  
Graft Loss ◽  
Human Leukocyte ◽  
Type I ◽  
Kidney Graft ◽  
Antibody Mediated Rejection ◽  
Increased Risk

Abstract Background and Aims Early graft failure (EGL) is a devastating complication of kidney transplantation. Patients with EGL have an increased risk of mortality of up to twelve times compared to patients who received grafts that survive beyond 30 days. Moreover, they may have become sensitized to antigens from the failed graft and that human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-transplantation occurs, there is no certainty regarding the recipient's immunological status. Hence, there could be an increased immunological risk with the consequent disturbance of the new graft's survival. Method We performed a retrospective single-center observational study in re-transplanted patients with EGL (defined as graft loss before 30 days from transplant) between January 1977 and November 2019 from our center to analyze the outcomes of rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation (occurred beyond those 30 days). Results: T here were 82 re-transplants after EGL. The median overall patient survival after re-transplantation was 32 years. Eight patients died within the first year. Among the mortality causes, there were four septic shocks, one cardiogenic shock, one massive pulmonary thromboembolism, one myocardial infarction, and one unknown cause. When analyzed for periods, death censored graft survival was 89% at one and five years after re-transplantation. One graft was lost at eight days due to antibody-mediated rejection (AMR), while there was one death with a functioning graft three months after re-transplantation secondary to a pulmonary embolism. Seventy-three late re-transplants occurred. When analyzed for periods, death censored graft survival was 81% and 69% at one and five years after re-transplantation, respectively. The median patient survival after late re-transplantation was 32 years. There were fewer deaths after rapid re-transplantation than late re-transplantation, but given the small number of cases in the former, this difference did not reach statistical significance (p = 0.3). There was no association between the timing of re-transplantation and an increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants did not share any incompatibilities between donors, four did share at least one HLA type I incompatibility, and one shared an incompatibility of HLA class I and class II. There were no T-cell mediated rejections (TCMR), and there was only one AMR in the rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs in the late re-transplantation group (p = 0.03 and p = 0.4, respectively). Conclusion Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor it diminishes long-term graft survival when compared to late re-transplantation.

scholarly journals Influence of Persistent Inflammation in Follow-Up Biopsies After Antibody-Mediated Rejection in Kidney Transplantation

2021 ◽  
Vol 8 ◽  
Author(s):  
Gaston J. Piñeiro ◽  
Enrique Montagud-Marrahi ◽  
José Ríos ◽  
Pedro Ventura-Aguiar ◽  
David Cucchiari ◽  
...  
Keyword(s):  
Graft Survival ◽  
Cox Regression ◽  
Graft Loss ◽  
Graft Function ◽  
Kidney Graft ◽  
Cox Regression Analysis ◽  
Antibody Mediated Rejection ◽  
Persistent Inflammation ◽  
Increased Risk

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.

Myocardial Noncompaction

2018 ◽  
Vol 69 (8) ◽  
pp. 2209-2212
Author(s):  
Alexandru Radu Mihailovici ◽  
Vlad Padureanu ◽  
Carmen Valeria Albu ◽  
Venera Cristina Dinescu ◽  
Mihai Cristian Pirlog ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Genetic Transmission ◽  
Asymptomatic Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold

2021 ◽  
pp. 2101410
Author(s):  
Alessandro N. Franciosi ◽  
Daniel Fraughen ◽  
Tomás P. Carroll ◽  
Noel G. McElvaney
Keyword(s):  
Risk Estimation ◽  
Specific Treatment ◽  
Weekly Administration ◽  
Risk Assessment Models ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Dosing Regimens ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Protective Threshold

AATD is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous purified pooled human AAT (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a “putative protective threshold” of 11 µM (0.57 g·L−1) in serum. This hypothesis has become central to the paradigm of AATD care, though its derivation and accuracy for defining risk of disease remain unclear.We review the literature and examine the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic.We found no data which demonstrates an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored.Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment.Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals.

scholarly journals Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death

2018 ◽  
Vol 7 (11) ◽  
pp. 425 ◽  
Author(s):  
Kumar Jayant ◽  
Isabella Reccia ◽  
Francesco Virdis ◽  
A. Shapiro
Keyword(s):  
Liver Transplantation ◽  
Blood Transfusion ◽  
Graft Survival ◽  
Meta Analysis ◽  
Donation After Cardiac Death ◽  
Clinical Trial Registry ◽  
Increased Risk ◽  
Increasing Demand ◽  
One Year ◽  
The Impact

Aim: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. Methods: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. Results: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). Conclusions: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.

scholarly journals Protocol Biopsies on de novo Renal-Transplants at 3 Months after Surgery: Impact on 5-Year Transplant Survival

2021 ◽  
Vol 10 (16) ◽  
pp. 3635
Author(s):  
Florian Terrec ◽  
Johan Noble ◽  
Hamza Naciri-Bennani ◽  
Paolo Malvezzi ◽  
Bénédicte Janbon ◽  
...  
Keyword(s):  
Graft Survival ◽  
Kidney Biopsy ◽  
De Novo ◽  
Immunosuppressive Regimen ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Kaplan Meier ◽  
Single Center Study ◽  
Protocol Biopsies

Background: In many centers, a protocol kidney biopsy (PKB) is performed at 3 months post-transplantation (M3), without a demonstrated benefit on death-censored graft survival (DCGS). In this study, we compared DCGS between kidney transplant recipients undergoing a PKB or without such biopsy while accounting for the obvious indication bias. Methods: In this retrospective, single-center study conducted between 2007 and 2013, we compared DCGS with respect to the availability and features of a PKB. We built a propensity score (PS) to account for PKB indication likelihood and adjusted the DCGS analysis on PKB availability and the PS. Results: A total of 615 patients were included: 333 had a PKB, 282 did not. In bivariate Kaplan–Meier survival analysis, adjusting for the availability of a PKB and for the PS, a PKB was associated with a better 5-year DCGS independently of the PS (p < 0.001). Among the PKB+ patients, 87 recipients (26%) had IF/TA > 0. Patients with an IF/TA score of 3 had the worst survival. A total of 144 patients (44%) showed cv lesions. Patients with cv2 and cv3 lesions had the worst 5-year DCGS. Conclusions: A M3 PKB was associated with improved graft survival independently of potential confounders. These results could be explained by the early treatment of subclinical immunological events. It could be due to better management of the immunosuppressive regimen.

scholarly journals Recent developments in psychosocial interventions for borderline personality disorder

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 561
Author(s):  
Christina M Temes ◽  
Mary C Zanarini
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Treatment Options ◽  
Specific Treatment ◽  
Psychosocial Interventions ◽  
Borderline Personality ◽  
Post Traumatic Stress ◽  
Treatment Needs ◽  
Specific Patient ◽  
Increased Risk

Borderline personality disorder (BPD) is a serious psychiatric disorder that affects multiple symptomatic domains and is associated with an increased risk of suicidality. Several empirically supported treatments for BPD have been developed in recent years for adults with BPD. More recent work has focused on tailoring or applying (or both) these existing treatments to specific patient populations, including patients with certain types of comorbidity (for example, BPD and post-traumatic stress disorder or antisocial personality disorder) and younger patients. Other work has involved developing treatments and models of treatment delivery that address concerns related to access of care. Relatedly, new adjunctive and technology-assisted interventions have been developed, adding to the growing repertoire of treatment options for these patients. Advances in the last several years address specific treatment needs and offer cost-efficient options for this diverse patient population.

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