Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

Background: ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens.

Methods: All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus.

A Prospective Randomized Trial on the Effect of Using an Electronic Monitoring Drug Dispensing Device to Improve Adherence and Compliance.

Background: Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities. Compliance describes the degree to which patients follow medical advice and take their medications. Adherence has been defined as the extent to which a patients' behavior coincides with clinical prescriptions.

An observational cohort study of the effect of hypertension on the loss of renal function in pediatric kidney recipients.

Background: Post-transplant hypertension impacts negatively on renal graft survival. Our primary objective was to analyze the effect of hypertension on the glomerular filtration rate (GFR) slope.

Methods: All clinical charts of children who underwent renal transplantation since the introduction of the routine use of ambulatory blood pressure monitoring (ABPM) were reviewed.

The outcome of the endothelial precursor cell crossmatch test in lymphocyte crossmatch positive and negative patients evaluated for living donor kidney transplantation.

The presence of human leukocyte antigen (HLA) and non-HLA antibodies (Abs) in kidney transplant recipients is associated with graft rejections. This study reports the results of an endothelial precursor cell crossmatch (EPCXM) test for detection of non-HLA Abs and its correlation to lymphocyte crossmatch (LXM) test results, the degree and type of sensitization, and transplantation (Tx) outcome in patients evaluated for living donor (LD) kidney transplantation (KTx). Patients were tested before any pre-transplantation (pre-Tx) treatment and at Tx.

Intentional ABO-incompatible heart transplantation: a case report of 2 adult patients.

Background: In 2009, we started to screen all patients on the heart transplant waiting list for the presence of blood group anti-A or anti-B antibodies. From our experience with ABO-incompatible kidney transplantation, we know that transplantation can safely be performed if the antibody level is reduced to a titer of immunoglobulin G (IgG) 1:8.

Methods: We decided to accept all patients with anti-A or anti-B antibody titer ≤1:8 for ABO-incompatible heart transplantation without any special pre-treatment and patients with antibody titers of IgG 1:16 and 1:32, provided 1 apheresis session could be performed immediately before transplantation.

Renal transplantation in infants and small children.

There are still concerns about renal transplantation in small children. The aim of this study was to identify prenatal data, underlying diseases, patient and graft survival, graft function and growth in young renal transplant recipients at our center. A retrospective analysis was performed on 50 kidney transplants performed during the period 1981-2008 in children weighing <13 kg.

ABO-incompatible kidney transplantation in children.

  We designed a new protocol to enable safe ABO-incompatible kidney transplantation. The new protocol utilizes antigen-specific immunoadsorption rather than unspecific plasma exchange to remove existing anti A/B antibodies and rituximab rather than splenectomy to prevent rebound of antibodies. Sixty patients have so far been successfully transplanted with this protocol and 10 of those have been children.

The efficacy of antigen-specific immunoadsorption and rebound of anti-A/B antibodies in ABO-incompatible kidney transplantation.

Background: As antigen-specific immunoadsorption (IA) using the Glycosorb®-ABO columns is becoming increasingly popular in ABO-incompatible (ABOi) transplantation, in this study, we retrospectively investigated the efficacy of Glycosorb®-ABO IA in vivo and ex vivo. We also assessed the risk of anti-A/B antibody (ABab) rebound before and after ABOi kidney transplantation.

Methods: A protocol for ABOi living donor kidney transplantation was used, combining four preoperative and three preemptive postoperative Glycosorb®-ABO IAs with rituximab and maintenance immunosuppression.

Isoagglutinin adsorption in ABO-incompatible transplantation.

As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. ABO-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as ABO-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier.

A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation.

Unlabelled: We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event.

Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation.

Background: Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection.

Methods: Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets.

Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial.

Background: Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant.

Methods: Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen.

ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: a 3-year follow-up.

Background: In 2001 a protocol for ABO-incompatible (ABOi) kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center, short-term results being comparable with those of ABO-compatible (ABOc) living donor kidney transplantation. Of greater importance, however, is long-term graft function, thus far not evaluated. The aim of this study was therefore to assess long-term results of this protocol.

A case of acute vascular rejection caused by endothelial-reactive non-HLA antibodies.

We describe a female patient who, despite negative conventional cross-matches, lost her first kidney graft in an acute humoral rejection. Prior to the second, AB0-incompatible (A1B to A1) living-donor kidney transplant, the patient had negative T- and B-cell cross-matches but had a positive donor-reactive endothelial cell cross-match. Following pre-transplant protein A and GlycoSorb-ABO immunoadsorptions to remove blood group B and anti-endothelial cell antibodies, Mabthera, and IVIG administrations, she was successfully transplanted.

Long-term results of ABO-incompatible kidney transplantation with antigen-specific immunoadsorption and rituximab.

ABO-incompatible (ABOi) kidney transplantation has gained a renewed interest during the past years. In 2001, a protocol for ABOi kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center. In this study long-term graft function using this protocol was assessed.

Preapheresis immunosuppressive induction: necessary or harmful?

In ABO-incompatible kidney transplantation, only a few studies have addressed the necessity, duration, and content of immunosuppressive induction therapy. At our center (Karolinska Institute, Stockholm, Sweden), using a preconditioning regimen consisting of 13 days of tacrolimus, mycophenolate mofetil, and prednisolone, we have investigated both short- and long-term renal allograft function (up to 28 days and 1 year after transplantation, respectively) and correlated them to tacrolimus 12-hr trough levels. In summary, during the first 28 days after transplantation, renal allograft function in the ABO-incompatible group was impaired when compared with that observed in the ABO-compatible group.

Pharmacodynamics of rituximab in kidney transplantation.

The B-cell depleting anti-CD20 antibody rituximab has become a therapeutic alternative in renal transplantation. However, understanding of the pharmacodynamics is limited. We have therefore studied the effect of single-dose rituximab, in combination with conventional triple immunosuppressive therapy, on the B-cell population in peripheral blood as well as in tissues, in kidney transplant recipients.

Present techniques for antibody removal.

Renal transplantation into a patient with a positive cytotoxic cross-match or with an incompatible blood group inevitably results in acute humoral rejection, unless the HLA or anti-A/B antibodies have been removed before transplantation. Although there are several procedures to remove HLA and anti-A/B antibodies, plasmapheresis and immunoadsorption are the most commonly used. In this report, presently available techniques for antibody removal are briefly reviewed.

The European experience.

A new protocol for ABO-incompatible kidney transplantation was introduced in 2001. In this protocol, antigen-specific immunoadsorption to remove existing AB antibodies is used in addition to rituximab to prevent rebound of antibodies and conventional immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). This protocol has successively been implemented in many European centers, primarily in Sweden and Germany but also in the UK, Switzerland, the Netherlands, Norway, Denmark, Greece and Spain, and almost 200 ABO-incompatible transplantations have now been performed.