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1.
Sci Rep ; 11(1): 8915, 2021 04 26.
Article in English | MEDLINE | ID: mdl-33903694

ABSTRACT

The diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.


Subject(s)
Endothelial Cells/metabolism , Flow Cytometry , Graft Rejection/blood , Hepatitis A Virus Cellular Receptor 1/blood , Kidney Transplantation , Adult , Allografts , Female , Humans , Male , Middle Aged , Time Factors
2.
J Crit Care ; 64: 37-44, 2021 08.
Article in English | MEDLINE | ID: mdl-33784577

ABSTRACT

All transplant recipients receive tacrolimus, mycophenolate and glucocorticoids and these drugs have many side-effects and drug-drug interactions. Common complications include surgical complications, infections, rejection and acute kidney injury. Infections as CMV and PJP can be prevented with prophylactic treatment. Given the complexity of organ transplant recipients a multi-disciplinary team of intensivists, surgeons, pharmacists and transplant specialists is essential. After heart transplantation a temporary pacemaker is required until the conduction system recovers. Stiffening of the heart and increased cardiac markers indicate rejection. An endomyocardial biopsy is performed via the right jugular vein, necessitating its preservation. For lung transplant patients, early intervention for aspiration is warranted to prevent chronic rejection. Risk of any infection is high, requiring active surveillance and intensive treatment, mainly of fungal infections. The liver is immunotolerant requiring lower immunosuppression. Transplantation surgery is often accompanied by massive blood loss and coagulopathy. Other complications include portal vein or hepatic artery thrombosis and biliary leakage or stenosis. Kidney transplant recipients have a high risk of cardiovascular disease and posttransplant anemia should be treated liberally. After postmortal transplantation, delayed graft function is common and dialysis is continued. Ureteral anastomosis complications can be diagnosed with ultrasound.


Subject(s)
Organ Transplantation , Transplant Recipients , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents , Intensive Care Units , Organ Transplantation/adverse effects , Renal Dialysis
3.
BJS Open ; 5(1)2021 01 08.
Article in English | MEDLINE | ID: mdl-33609374

ABSTRACT

BACKGROUND: The 5-year graft survival rate of donor kidneys transplanted in the Eurotransplant Senior Program (ESP) is only 47 per cent. Normothermic machine perfusion (NMP) may be a new preservation technique that improves graft outcome. This pilot study aimed to assess safety and feasibility of this technique within the ESP. METHODS: Recipients were eligible for inclusion if they received a donor kidney within the ESP. Donor kidneys underwent 2 h of oxygenated NMP with a red cell-based solution at 37°C, additional to standard-of-care preservation (non-oxygenated hypothermic machine perfusion). The primary outcome was the safety and feasibility of NMP. As a secondary outcome, graft outcome was investigated and compared with that in a historical group of patients in the ESP and the contralateral kidneys. RESULTS: Eleven patients were included in the NMP group; the function of eight kidneys could be compared with that of the contralateral kidney. Fifty-three patients in the ESP, transplanted consecutively between 2016 and 2018, were included as controls. No adverse events were noted, especially no arterial thrombosis or primary non-function of the transplants. After 120 min of oxygenated NMP, median flow increased from 117 (i.q.r. 80-126) to 215 (170-276) ml/min (P = 0.001). The incidence of immediate function was 64 per cent in the NMP group and 40 per cent in historical controls (P = 0.144). A significant difference in graft outcome was not observed. DISCUSSION: This pilot study showed NMP to be safe and feasible in kidneys transplanted in the ESP. A well powered study is warranted to confirm these results and investigate the potential advantages of NMP on graft outcome.


Subject(s)
Kidney Transplantation/methods , Kidney , Organ Preservation/methods , Perfusion/methods , Aged , Delayed Graft Function , Feasibility Studies , Female , Graft Rejection , Graft Survival , Humans , Kidney Transplantation/adverse effects , Male , Organ Preservation/instrumentation , Perfusion/instrumentation , Pilot Projects , Prospective Studies
4.
Am J Transplant ; 15(2): 407-16, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25612493

ABSTRACT

We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double-blind, placebo-controlled study, 280 adult renal transplant patients were randomized between a single dose of rituximab (375 mg/m(2)) or placebo during transplant surgery. Patients were stratified according to panel-reactive antibody (PRA) value and rank number of transplantation. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroids. The primary endpoint was the incidence of biopsy proven acute rejection (BPAR) within 6 months after transplantation. The incidence of BPAR was comparable between rituximab-treated (23/138, 16.7%) and placebo-treated patients (30/142, 21.2%, p = 0.25). Immunologically high-risk patients (PRA >6% or re-transplant) not receiving rituximab had a significantly higher incidence of rejection (13/34, 38.2%) compared to other treatment groups (rituximab-treated immunologically high-risk patients, and rituximab- or placebo-treated immunologically low-risk (PRA ≤ 6% or first transplant) patients (17.9%, 16.4% and 15.7%, p = 0.004). Neutropenia (<1.5 × 10(9) /L) occurred more frequently in rituximab-treated patients (24.3% vs. 2.2%, p < 0.001). After 24 months, the cumulative incidence of infections and malignancies was comparable. A single dose of rituximab as induction therapy did not reduce the overall incidence of BPAR, but might be beneficial in immunologically high-risk patients. Treatment with rituximab was safe.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adult , B-Lymphocytes/pathology , Biopsy , Double-Blind Method , Female , Graft Rejection/pathology , Humans , Incidence , Kidney/pathology , Male , Middle Aged , Remission Induction , Rituximab , Treatment Outcome
5.
Transpl Immunol ; 31(4): 207-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25270152

ABSTRACT

Traditionally, antirejection therapy in organ transplantation has mainly been directed at T cells. During recent years, the role of B cells in acute rejection has attracted more attention. In the Radboud University Medical Center (Nijmegen, The Netherlands) we performed a randomized, placebo controlled study to assess the efficacy and safety of rituximab as induction therapy after renal transplantation. In parallel we investigated the effects of rituximab on the numbers and function of B and T cells. An overview of the results, which have largely been published in peer reviewed papers, is presented below.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Graft Rejection/drug therapy , Graft Rejection/immunology , Humans , Lymphocyte Activation/immunology , Lymphocyte Count , Placebos , Rituximab , T-Lymphocytes/cytology , T-Lymphocytes/immunology
6.
Am J Transplant ; 13(1): 192-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23167538

ABSTRACT

Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0 mg/kg bodyweight i.v. for 10-14 days; n = 20). We assessed treatment-failure (graft loss, lack of improvement of graft function or need for additional anti-rejection treatment), infections during the first 3 months after treatment and infusion-related side effects. In both groups, the median time-interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion-related side-effects in three alemtuzumab-treated patients (27%), and more severe infusion-related side effects in 17 RATG-treated patients (85%, p = 0.013). Drug related costs of alemtuzumab-treatment were lower than of RATG-treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid-resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant a prospective trial.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/prevention & control , Kidney Transplantation , Steroids/therapeutic use , Adult , Alemtuzumab , Female , Humans , Male
7.
Neth J Med ; 70(8): 370-3, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23065985

ABSTRACT

A 45-year-old male recipient of a renal allograft was admitted because of a giant oesophageal ulcer coinciding with leucopoenia. An extensive workup revealed no explanation for the ulcer and leucopoenia. Our final diagnosis by exclusion was an idiopathic giant oesophageal ulcer and late-onset neutropenia as consequences of rituximab induction therapy given during the transplant procedure. The patient fully recovered after treatment with prednisone. However, after four months, the ulcer and leucopoenia recurred and again successfully responded to treatment with prednisone.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/adverse effects , Esophageal Diseases/etiology , Kidney Transplantation/adverse effects , Leukopenia/etiology , Prednisone/therapeutic use , Ulcer/etiology , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Esophageal Diseases/pathology , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use , Leukopenia/chemically induced , Leukopenia/drug therapy , Male , Middle Aged , Perioperative Care/adverse effects , Perioperative Care/methods , Rituximab , Ulcer/chemically induced , Ulcer/drug therapy
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