Trained immunity suppression determines kidney allograft survival.

The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli.

Disparities in kidney transplantation accessibility among immigrant populations in Europe: A systematic review and meta-analysis.

Background And Objectives: Disparities in access to healthcare for patients with an immigration background are well-known. The aim of this study was to determine whether disparities among immigrant populations translate into a relative difference in the number of kidney transplants (KT) performed in documented immigrant patients (first and second generation) relative to native-born patients in Europe.

Methods: A literature search was performed in PubMed from inception to 11-10-2022.

Endothelial Cell Replacement of Human Veins, Modeling Vascular Repair and Endothelial Cell Chimerism.

Allogeneic transplant organs are potentially highly immunogenic. The endothelial cells (ECs) located within the vascular system serve as the primary interface between the recipient's immune system and the donor organ, playing a key role in the alloimmune response. In this study, we investigated the potential use of recipient-derived ECs in a vein recellularization model.

Monitoring antihypertensive drug concentrations to determine nonadherence in hypertensive patients with or without a kidney transplant.

Background: Nonadherence to antihypertensive drugs (AHDs) is a major contributor to pseudo-resistant hypertension. The primary objective of this study was to determine the prevalence of nonadherence to AHDs among patients visiting the nephrology and vascular outpatient clinics.

Methods: Patients were eligible to participate in this prospective observational study if they used at least two AHDs that could be measured with a validated UHPLC-MS/MS method and had an office blood pressure at least 140 and/or at least 90 mmHg.

Additional Normothermic Machine Perfusion Versus Hypothermic Machine Perfusion in Suboptimal Donor Kidney Transplantation: Protocol of a Randomized, Controlled, Open-Label Trial.

Introduction: Ageing of the general population has led to an increase in the use of suboptimal kidneys from expanded criteria donation after brain death (ECD-DBD) and donation after circulatory death (DCD) donors. However, these kidneys have inferior graft outcomes and lower rates of immediate function. Normothermic machine perfusion (NMP) may improve outcomes of these suboptimal donor kidneys.

A comparison between combined liver kidney transplants to liver transplants alone: A systematic review and meta-analysis.

Background: Since the introduction of the Model for End-stage Liver disease criteria in 2002, more combined liver kidney transplants are performed. Until 2017, no standard allocation policy for combined liver kidney transplant (CLKT) was available and each transplant center decided eligibility for CLKT or liver transplant alone (LTA) on a case-by-case basis. The aim of this systematic review was to compare the clinical outcomes of CLKT compared to LTA in patients with renal dysfunction.

Rituximab in Membranous Nephropathy.

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients.

Comparison of Alemtuzumab and Anti-thymocyte Globulin Treatment for Acute Kidney Allograft Rejection.

Rabbit anti-thymocyte globulin (rATG) is currently the treatment of choice for glucocorticoid-resistant, recurrent, or severe acute allograft rejection (AR). However, rATG is associated with severe infusion-related side effects. Alemtuzumab is incidentally given to kidney transplant recipients as treatment for AR.

Costimulation Blockade in Kidney Transplant Recipients.

Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success.

Risk of Nephrotic Syndrome for Non-Steroidal Anti-Inflammatory Drug Users.

Background And Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with AKI. Their association with nephrotic syndrome has not been systematically studied. This study aimed to assess the risk of nephrotic syndrome associated with NSAID use.

Successful Treatment of Severe Hyperammonaemia with Ultra-High Dose Continuous Veno-Venous Haemodiafiltration.

Hyperammonaemia is a severe condition and often requires a multimodal treatment regimen. Dialysis has been described as a potential treatment option, but currently it is not the standard of care. In this report, we describe a case of a 40-year-old postpartum woman who developed severe hyperammonaemia due to liver failure and acute kidney injury (AKI) combined with a large intra-abdominal haematoma producing nitrogen waste products.

Absence of Intragraft B Cells in Rejection Biopsies After Rituximab Induction Therapy: Consequences for Clinical Outcome.

Background: The pathophysiological role of intragraft B cells during renal allograft rejection is unclear.

Methods: We studied B-cell infiltration during acute rejection in 53 patients who participated in a clinical trial in which adult renal transplant patients were randomized between a single intraoperative dose of rituximab (375 mg/m) or placebo as induction therapy. Two independent pathologists scored all biopsies in a blinded fashion according to the Banff classification and scored for the presence of B cells and plasma cells using CD79a and CD138 as markers.

Cytokine Release After Treatment With Rituximab in Renal Transplant Recipients.

Background: Treatment with rituximab may be accompanied by a systemic cytokine release. We studied the effects of a single dose of rituximab on cytokine levels in transplant patients and examined the underlying mechanism.

Methods: Twenty renal transplant recipients (10 rituximab-treated, 10 placebo-treated) were recruited from a randomized clinical trial.

Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy.

Background: Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B-cell phenotype and function are limited.

Methods: In a randomized double-blind placebo-controlled study to prevent renal allograft rejection, patients were treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose of rituximab or placebo during transplant surgery.

The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production.

In renal transplantation, IL-17 production by T-cells might be dependent on the presence of B-cells. Therefore, the effect of in vivo B-cell depletion on ex-vivo IL-17 production was investigated. Twenty patients undergoing living-donor renal transplantation were recruited from a larger cohort of patients participating in a randomized, double-blind trial.

Insulin requirement after a renal transplant in patients with type 2 diabetes: the choice of calcineurin inhibitors.

Objectives: Hyperglycemia is a common adverse event of immunosuppressive drugs used in organ transplant. Because cyclosporine is less diabetogenic than tacrolimus is, cyclosporine may be preferred in patients with pre-existing diabetes mellitus type 2, to prevent insulin treatment after a transplant.

Patients And Methods: From March 2005 to June 2011, adult renal transplant patients with pre-existing diabetes mellitus type 2, who were not treated with insulin before a transplant, were treated with cyclosporine in combination with mycophenolate mofetil and corticosteroids.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

Objectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess.

Anti-T-cell antibodies for the treatment of acute rejection after renal transplantation.

Introduction: Given the central role of T cells in the alloimmune response, anti-T-cell antibodies retain a prominent place in the treatment of renal allograft rejection. During the past decades, many anti-T-cell antibodies have emerged and subsequently left the field of solid organ transplantation, but rabbit-antithymocyte globulin (ATG) and the humanized anti-CD52 monoclonal rat antibody alemtuzumab have remained.

Areas Covered: This article reviews the literature about the use of ATG and alemtuzumab for the treatment of acute rejection after renal transplantation.

[Reimbursement for alternative medical treatment in the Netherlands, incomprehensible].

It is remarkable that, at a time when not only doctors but also the Health Care Inspectorate (IGZ) and the health insurance companies are paying increasing attention to the quality of conventional medicine, many alternative methods of treatments without a scientific basis are accepted in the Netherlands. Even though it has been conclusively demonstrated that most alternative therapies do not work and despite the absence of scientific proof of the safety and efficacy of alternative treatments, health insurance companies do often reimburse the incurred costs. Because the safety of alternative therapies is not guaranteed, these are neither in the interest of the patient nor of society.

Use of monoclonal antibodies in renal transplantation.

Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects.