scholarly journals Infectious complications and graft outcome following treatment of acute antibody-mediated rejection after kidney transplantation: A nationwide cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250829
Author(s):  
Nancy Perrottet ◽  
Mario Fernández-Ruiz ◽  
Isabelle Binet ◽  
Michael Dickenmann ◽  
Suzan Dahdal ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Transplantation ◽  
Real Life ◽  
Severe Infection ◽  
Intravenous Immunoglobulins ◽  
Infectious Complications ◽  
Treatment Recommendation ◽  
Accurate Information ◽  
Significant Heterogeneity ◽  
Antibody Mediated Rejection

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

scholarly journals Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study

2020 ◽  
Vol 31 (9) ◽  
pp. 2193-2204 ◽  
Author(s):  
Aleksandar Senev ◽  
Maarten Coemans ◽  
Evelyne Lerut ◽  
Vicky Van Sandt ◽  
Johan Kerkhofs ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Transplantation ◽  
Graft Failure ◽  
De Novo ◽  
Multivariable Analysis ◽  
Hla Antibodies ◽  
Transplant Outcomes ◽  
Antibody Mediated Rejection ◽  
Kidney Recipients ◽  
Hla Dq

BackgroundIn kidney transplantation, evaluating mismatches of HLA eplets—small patches of surface-exposed amino acids of the HLA molecule—instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes.MethodsTo evaluate the effect of number of eplet mismatches (mismatch load) on de novo formation of donor-specific HLA antibodies (DSAs) and transplant outcomes, we conducted a cohort study that included consecutive adult kidney recipients transplanted at a single center from March 2004 to February 2013. We performed retrospective high-resolution genotyping of HLA loci of 926 transplant pairs and used the HLAMatchmaker computer algorithm to count HLA eplet mismatches.ResultsDe novo DSAs occurred in 43 (4.6%) patients. Multivariable analysis showed a significant independent association between antibody-verified eplet mismatch load and de novo DSA occurrence and graft failure, mainly explained by DQ antibody-verified eplet effects. The association with DQ antibody-verified eplet mismatches was linear, without a safe threshold at which de novo DSA did not occur. Odds for T cell– or antibody-mediated rejection increased by 5% and 12%, respectively, per antibody-verified DQ eplet mismatch.ConclusionsEplet mismatches in HLA-DQ confer substantial risk for de novo DSA formation, graft rejection, and graft failure after kidney transplantation. Mismatches in other loci seem to have less effect. The results suggest that antibody-verified HLA-DQ eplet mismatch load could be used to guide personalized post-transplant immunosuppression. Adoption of molecular matching for DQA1 and DQB1 alleles could also help to minimize de novo DSA formation and potentially improve transplant outcomes.

scholarly journals Infectious Complications in Adult ABO-Incompatible Liver Transplantation: Our Preliminary Experience

2020 ◽  
Vol 104 (3-4) ◽  
pp. 176-181
Author(s):  
Hironori Hayashi ◽  
Hiroyuki Takamura ◽  
Hidehiro Tajima ◽  
Yoshinao Ohbatake ◽  
Shinichi Nakanuma ◽  
...  
Keyword(s):  
Treatment Protocol ◽  
Prophylactic Antibiotic ◽  
Severe Infection ◽  
Infectious Complications ◽  
Infusion Therapy ◽  
Donor Liver ◽  
Antibody Mediated Rejection ◽  
Increased Risk ◽  
Liver Transplantations ◽  
Life Threatening

The number of ABO-incompatible living donor liver transplantations (ABO-I LDLT) has increased owing to the use of preoperative rituximab for immunosuppression. However, controversy remains regarding adequate immunosuppression owing to rejection and infection. Here, we present 5 cases of our ABO-I LDLT experience, emphasizing rejection and infectious complications, retrospectively. The treatment protocol included prophylactic rituximab followed by plasma exchange prior to transplantation, splenectomy, and immunosuppressive and prophylactic antibiotic regimens after transplantation. Four of the 5 patients also received local infusion therapy via the portal vein. Neither hyperacute nor antibody-mediated rejection occurred. All grafts were functioning well at discharge. Rehospitalization was required for 2 patients due to severe infection within 6 months of transplantation. Invasive aspergillosis was successfully treated in 1 patient, but the other patient died from severe sepsis with overwhelming postsplenectomy infection syndrome. Our results confirm that, although improved immunosuppressive therapy markedly reduces rejection in ABO-I LDLT, it is also associated with an increased risk of various life-threatening infections.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

scholarly journals Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Current Knowledge ◽  
Real Life ◽  
Response To Therapy ◽  
Significant Heterogeneity ◽  
Intestinal Damage ◽  
Biological Therapies ◽  
Early Markers ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

scholarly journals Treatment with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: data from the COVID-PREDICT cohort study in The Netherlands

2021 ◽  
Author(s):  
Rick I. Meijer ◽  
Trynke Hoekstra ◽  
Niels C. Gritters van den Oever ◽  
Suat Simsek ◽  
Joop P. van den Bergh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Hospital Admission ◽  
Clinical Outcomes ◽  
Primary Outcome ◽  
Infectious Complications ◽  
Glucose Lowering ◽  
Diabetes Severity ◽  
Outcome Mortality

Abstract Purpose Inhibition of dipeptidyl peptidase (DPP-)4 could reduce coronavirus disease 2019 (COVID-19) severity by reducing inflammation and enhancing tissue repair beyond glucose lowering. We aimed to assess this in a prospective cohort study. Methods We studied in 565 patients with type 2 diabetes in the CovidPredict Clinical Course Cohort whether use of a DPP-4 inhibitor prior to hospital admission due to COVID-19 was associated with improved clinical outcomes. Using crude analyses and propensity score matching (on age, sex and BMI), 28 patients using a DPP-4 inhibitor were identified and compared to non-users. Results No differences were found in the primary outcome mortality (matched-analysis = odds-ratio: 0,94 [95% confidence interval: 0,69 – 1,28], p-value: 0,689) or any of the secondary outcomes (ICU admission, invasive ventilation, thrombotic events or infectious complications). Additional analyses comparing users of DPP-4 inhibitors with subgroups of non-users (subgroup 1: users of metformin and sulphonylurea; subgroup 2: users of any insulin combination), allowing to correct for diabetes severity, did not yield different results. Conclusions We conclude that outpatient use of a DPP-4 inhibitor does not affect the clinical outcomes of patients with type 2 diabetes who are hospitalized because of COVID-19 infection.

scholarly journals Letermovir Primary Prophylaxis in High-Risk Hematopoietic Cell Transplant Recipients: A Matched Cohort Study

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 372
Author(s):  
Léna Royston ◽  
Eva Royston ◽  
Stavroula Masouridi-Levrat ◽  
Nathalie Vernaz ◽  
Yves Chalandon ◽  
...  
Keyword(s):  
Renal Function ◽  
Cohort Study ◽  
High Risk ◽  
Real Life ◽  
Primary Prophylaxis ◽  
Hematopoietic Cell ◽  
P Value ◽  
Cell Transplant ◽  
Matched Cohort ◽  
Matched Cohort Study

Background: Real-life data on the administration of letermovir as cytomegalovirus (CMV) primary prophylaxis after allogeneic hematopoietic cell transplantation (HCT) remain limited. Methods: We conducted a retrospective single-center matched cohort study, comparing consecutive high-risk allogeneic HCT recipients (cases) receiving primary prophylaxis with letermovir and untreated matched historical controls, during a study period of 180 days. The primary outcome was the incidence of clinically significant (cs) CMV infection. Secondary outcomes included duration and costs of CMV-antiviral treatments, hospital resource utilization, hematology and laboratory parameters. Results: Letermovir prophylaxis decreased csCMV infection incidence from 82.7% (controls) to 34.5% (cases; p-value < 0.0001). Controls were more likely to have >1 episode of csCMV infection (59.6%) compared to cases (11.5%; p-value < 0.0001). Letermovir was associated with: shorter overall CMV-associated treatment duration (49 days vs. 77.8 days; p-value: 0.02) and a trend for lower costs of CMV-associated treatments ($4096 vs. $9736; p-value: 0.07) and reduced length of stay (44.8 days vs. 59.8 days; p-value: 0.16). Letermovir administration was associated with significantly shorter duration (27.3 days vs. 57.1 days; p-value: 0.008) and lower costs ($1089 vs. $2281; p-value: 0.008) of valganciclovir treatment. Compared to controls, higher platelet counts were observed in cases (138 G/L vs. 92 G/L; p-value: 0.03) and renal function was improved (94 mL/min/1.73 m2 vs. 74 mL/min/1.73 m2; p-value: 0.006). Conclusions: Primary anti-CMV letermovir prophylaxis decreased the incidence of csCMV infection and the administration of CMV-associated treatments and costs, particularly those associated with valganciclovir. An effect of letermovir on platelet reconstitution and renal function of csCMV post-HCT was observed and needs further investigation.

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