scholarly journals SARS-CoV-2-specific Humoral and Cell-mediated Immune Responses after Immunization with Inactivated COVID-19 Vaccine in Kidney Transplant Recipients (CVIM 1 Study)

2021 ◽  
Author(s):  
Jackrapong Bruminhent ◽  
Chavachol Sethaudom ◽  
Pongsathon Chaumdee ◽  
Sarinya Boongird ◽  
Sasisopin Kiertiburanakul ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Calcineurin Inhibitors ◽  
Neutralizing Antibody ◽  
Cell Mediated Immunity ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Responses ◽  
Clinical Trials Registry

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 non-transplant controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median age of KT recipients was 50 years (IQR, 42 to 54) and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median time since transplant was 4.5 years (IQR, 2 to 9.5). Among 35 KT patients, anti-RBD IgG titer after vaccination was not significantly different to baseline, but was significantly lower than in controls (7.8 [95%CI 0.2 to 15.5] vs 2,691 [95%CI 1,581 to 3,802], p<0.001) as well as the percentage of surrogate virus neutralizing antibody inhibition (2 [95% CI -1 to 6] vs 71 [95%CI 61 to 81], p<0.001). However, the mean of SARS-CoV-2 mixed peptides-specific T-cell responses measured by enzyme-linked immunospot assays was significantly increased compared with baseline (66 [95%CI 36 to 99] vs. 34 [95%CI 19 to 50] T-cells/10^6 PBMCs, p=0.02) and comparable to that in controls. Our findings revealed weak HMI and marginal CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccine. (Thai Clinical Trials Registry, TCTR20210226002).

scholarly journals B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

2021 ◽  
Author(s):  
Eva Schrezenmeier ◽  
Hector Rincon-Arevalo ◽  
Ana-Luisa Stefanski ◽  
Alexander Potekhin ◽  
Henriette Staub-Hohenbleicher ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
The Third ◽  
Cellular Analysis ◽  
Cell Immunity

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

Impact of a Clinical Solid Organ Transplant Pharmacist on Tacrolimus Nephrotoxicity, Therapeutic Drug Monitoring, and Institutional Revenue Generation in Adult Kidney Transplant Recipients

2016 ◽  
Vol 26 (4) ◽  
pp. 314-321 ◽  
Author(s):  
Shawn P. Griffin ◽  
Joelle E. Nelson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Kidney Transplant ◽  
Drug Monitoring ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Adult Kidney

Context: Tacrolimus requires close therapeutic drug monitoring (TDM) to ensure efficacy and minimize adverse effects. Pharmacists are uniquely positioned on transplant teams to interpret levels and recommend therapy modifications. Their impact in the immediate postoperative setting has not been described previously. Objective: To evaluate the impact of a clinical solid organ transplant pharmacist on nephrotoxicity, TDM, and revenue generation in adult kidney transplant recipients on tacrolimus. Design, Setting, and Patients: Retrospective assessment of adult kidney transplant recipients at University of Florida Health Shands Hospital. Intervention: A transplant pharmacist rounded 5 days a week and made medication recommendations on transplant recipients—including tacrolimus dose modifications based on levels. Pharmacy services were expanded to include medication reconciliation, medication counseling, and delivery of discharge medications to bedside. Main Outcome Measure: Incidence of nephrotoxicity during tacrolimus exposure. Results: Of the 70 kidney transplant recipients in the postpharmacist cohort, 18 (25.7%) experienced nephrotoxicity while on tacrolimus, compared to 18 (25%) of the 72 in the prepharmacist cohort ( P = .922). A significantly greater proportion of recipients who experienced nephrotoxicity were male, had hypertension, or experienced delayed or slow graft function. The rate of appropriately drawn tacrolimus troughs significantly increased from 23.4% to 30.3% in the postpharmacist cohort ( P < .001). The median outpatient pharmacy revenue generated per recipient significantly increased from US$345.49 (interquartile range [IQR]: 0-4727.56) to US$4834.95 per recipient (IQR: 3592.78-6224.60; P < .001). The length of stay (7 days, IQR: 6-9, vs 8 days, IQR: 6-9; P = .107) and the 30-day readmission rate were similar between groups (20.8% vs 21.4%; P = .931).

scholarly journals SARS-CoV-2 vaccine effectiveness in immunosuppressed kidney transplant recipients

2021 ◽  
Author(s):  
Hiam Chemaitelly ◽  
Sawsan AlMukdad ◽  
Jobin Paravila Joy ◽  
Houssein H. Ayoub ◽  
HADI M. YASSINE ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Vaccine Effectiveness ◽  
Public Healthcare ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Vaccine Protection ◽  
High Level ◽  
Dose Vaccine

COVID-19 vaccine protection against infection in immunosuppressed solid organ transplant recipients is unknown but possibly weak with the low proportion of these patients mounting a robust humoral and cellular immune response after vaccination. Using a retrospective cohort study design with cross-over, we assessed vaccine effectiveness among 782 kidney transplant recipients registered at Hamad Medical Corporation, the national public healthcare provider in Qatar, where the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been used in the national immunization campaign. Vaccine effectiveness against any SARS-CoV-2 infection was estimated at 46.6% (95% CI: 0.0-73.7%) ≥14 days after the second dose, 66.0% (95% CI: 21.3-85.3%) ≥42 days after the second dose, and 73.9% (95% CI: 33.0-89.9%) ≥56 days after the second dose. Vaccine effectiveness against any severe, critical, or fatal COVID-19 disease was estimated at 72.3% (95% CI: 0.0-90.9%) ≥14 days after the second dose, 85.0% (95% CI: 35.7-96.5%) ≥42 days after the second dose, and 83.8% (95% CI: 31.3-96.2%) ≥56 days after the second dose. Most vaccine breakthrough infections occurred in the first few weeks after receiving the first and/or second dose. Vaccine effectiveness reached considerable levels in kidney transplant recipients, but vaccine protection mounted slowly and did not reach a high level until several weeks after the second dose.

scholarly journals Antibody response to a fourth mRNA Covid-19 vaccine boost in weak responder kidney transplant recipients

2021 ◽  
Author(s):  
Sophie Caillard ◽  
Olivier Thaunat ◽  
Ilies Benotmane ◽  
christophe masset ◽  
Gilles Blancho
Keyword(s):  
Antibody Response ◽  
Kidney Transplant ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Immunosuppressive Drugs ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Fourth Dose ◽  
Us Fda

The US FDA has recently authorized immunocompromised people to receive a third dose of mRNA Covid-19 vaccine following the two-doses regimen to further boost protection. Unfortunately, a non-negligible proportion of people treated with immunosuppressive drugs either do not respond or show only a weak response after a third boost and should, therefore, still be considered at risk of severe Covid-19. As of June 2021, we were granted the opportunity to offer a fourth vaccine dose to French solid organ transplant recipients who still showed a weak antibody response after the third dose. In this multicenter study, we demonstrate that that the protection conferred by a fourth dose is adequate for the majority of kidney transplant recipients

scholarly journals Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

2020 ◽  
Vol 8 (1) ◽  
pp. e000908 ◽  
Author(s):  
Megan H Trager ◽  
Shana M Coley ◽  
Geoffrey Dube ◽  
Shaheer Khan ◽  
Matthew Ingham ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Solid Organ ◽  
Combination Immunotherapy ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Solid Organ Transplant Recipients

BackgroundImmune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.Case presentationsHere we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.ConclusionsThese cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.Trial Registration numberNCT03816332.

scholarly journals A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thaninee Prasoppokakorn ◽  
Jakapat Vanichanan ◽  
Roongruedee Chaiteerakij ◽  
Kamonwan Jutivorakool ◽  
Suwasin Udomkarnjananun ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Dose Regimen ◽  
Hepatitis A ◽  
Controlled Trial ◽  
Seroconversion Rate ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Solid Organ Transplant Recipients

AbstractHepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.

scholarly journals B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

2021 ◽  
pp. ASN.2021070966
Author(s):  
Eva Schrezenmeier ◽  
Hector Rincon-Arevalo ◽  
Ana-Luisa Stefanski ◽  
Alexander Potekhin ◽  
Henriette Staub-Hohenbleicher ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
The Third ◽  
Cellular Analysis ◽  
Cell Immunity

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

scholarly journals COVID-19 Severity and Mortality in Solid Organ Transplantation: Differences between Liver, Heart, and Kidney Recipients

2021 ◽  
Vol 2 (3) ◽  
pp. 296-303 ◽  
Author(s):  
Ricardo Wesley Alberca ◽  
Gabriela Gama Freire Alberca ◽  
Lucas Chaves Netto ◽  
Raquel Leão Orfali ◽  
Sarah Cristina Gozzi-Silva ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Kidney Transplant ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Solid Organ Transplant Recipients ◽  
Liver Transplant Recipients

The infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can generate a wide spectrum of clinical manifestations ranging from asymptomatic to severe respiratory and systemic disease with coagulation disorder named coronavirus disease 2019 (COVID-19). Patients with comorbidities have been identified as risk groups for severe COVID-19, also having a higher death risk. Previous reports have conflicting results regarding if solid organ transplant recipients present an increased risk for COVID-19. Nevertheless, previous investigations failed to distinguish between different organs received or made a longitudinal investigation on those patients. We recruited 39 solid organ transplant recipients: 25 kidney transplant recipients, 7 heart transplant recipients, and 7 liver transplant recipients and 25 age-matched non-transplant COVID-19 patients without comorbidities (control group) and compared daily laboratory data in addition to performing survival analysis. Heart and kidney transplant recipients presented an increase in several COVID-19 severity-associated biomarkers, such as neutrophil-to-lymphocyte ratio and thrombocytopenia, in comparison to the control group and liver transplant recipients. Heart and kidney transplant recipients also presented an increase in the need for intensive care and invasive mechanical ventilation during the disease’s course. Importantly, heart and kidney transplant recipients presented a higher mortality rate in comparison to liver transplant recipients and non-transplant recipients. In our cohort, heart and kidney transplant recipients presented a difference in clinical characteristics and survival rate in comparison to liver transplant recipients. Further investigation involving immune response to SARS-CoV-2 in solid organ recipients should consider and separate patients according to the organ grafted.

scholarly journals Validation and Adaptation of the “Modified Transplant Symptom Occurrence and Symptom Distress Scale” for Kidney Transplant Recipients

2020 ◽  
Vol 17 (19) ◽  
pp. 7348
Author(s):  
Jisu Kim ◽  
Insil Jang
Keyword(s):  
Construct Validity ◽  
Kidney Transplant ◽  
Content Validity ◽  
Organ Transplant ◽  
Symptom Distress ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Symptom Distress Scale ◽  
Distress Scale

The aim was to adapt and validate the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) for kidney transplant recipients undergoing immunosuppressive therapy in Korea. The MTSOSD-59R has been used with solid organ transplant recipients globally to assess the adverse effects of immunosuppressive medication. A descriptive cross-sectional design was used. MTSOSD-59R was first translated, and pilot tested. Next, content validity was established with nine organ transplant experts. Then, from October 2017 to October 2018, the Korean MTOSOSD-59R was administered to a convenience sample of 122 kidney transplant recipients recruited from a single center. Ridit analysis was used to measure symptom occurrence and distress. The known-group approach was used to test the construct validity using Mann–Whitney U tests for between-group comparisons. The content validity index for MTSOSD-59R was 0.98, and known-group validity was confirmed. The split-half Spearman–Brown corrected reliability coefficient was 0.902 for symptom occurrence and 0.893 for symptom distress. The four most frequent and distressing symptoms were fatigue, lack of energy, thinning hair, and erectile dysfunction (male). Results suggest this Korean MTSOSD-59R adaptation has adequate language, construct validity, and reliability to gather meaningful information from kidney transplant recipients in Korea.

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

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