Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

Background: When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal.

An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survival.

Background: Blood transfusions have the potential to improve graft survival, induce sensitization, and transmit infections. Current clinical practice is to minimize transfusions in renal transplantation candidates, but it is unclear if the evidence continues to support pre-transplant transfusion avoidance. Changes in the Medicare prospective payment system may increase transfusion rates.

Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention.

Sensitization by previous pregnancies or transplants is considered unavoidable, but it is transfusions given to these patients that leads most often to broad sensitization. Both leukocytes and red cells carry a significant HLA antigen load, and residual leukocytes and/or red cell HLA may explain why leukocyte-reduced units are unable to prevent sensitization to any significant degree. Prevention of sensitization will require a more active effort to avoid blood transfusions, whenever possible.

Human leukocyte antigen sensitization after transplant loss: timing of antibody detection and implications for prevention.

Graft failure is a major cause of broad sensitization but it is not clear whether sensitization occurs immediately after transplant loss or other factors (transfusions, nephrectomy, etc.) trigger it subsequently. Human leukocyte antigen antibodies were measured in 104 patients who lost a kidney transplant.

Effect of IVIG administration on complement activation and HLA antibody levels.

The objective of the present study was to determine if there are changes on complement (C) activation and concentration of HLA antibodies (Abs) in patients treated with intravenous immunoglobulin (IVIG). The patients evaluated were given IVIG as treatment of Ab-mediated rejection or desensitization. The patients' sera obtained before and after IVIG administration were tested for their effects on the deposition of both IgG (HLA Abs) and C3b (C activation) as measured by flow cytometry on T cells.

Hypomethylating agent induction therapy followed by hematopoietic cell transplantation is feasible in patients with myelodysplastic syndromes.

Disease remission in patients with myelodysplastic syndromes can be achieved with azanucleosides, which act as pyrimidine analogs and hypomethylating agents. However, despite treatment with azanucleoside induction, patients with myelodysplastic syndromes nearly always relapse. Allogeneic hematopoietic cell transplantation (HCT) can be curative, but it is risky.

A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients.

Introduction: Human leukocyte antigen (HLA) matching has been de-emphasized in the allocation of renal allografts and further discounting is planned in the new United Network of Organ Sharing kidney allocation model. An unforeseen consequence of poorer matching could be increased sensitization for candidates pursuing retransplantation.

Methods: We examined candidates listed in the United States from 1988 to 2007 from the Scientific Renal Transplant Registry (SRTR) database that were relisted after loss of a primary kidney transplant (n=15,980).

Reduced-intensity conditioning using fludarabine with either antithymocyte globulin and BU, or low-dose TBI allowing allogeneic hematopoietic SCT.

In a single-center study, we analyzed the outcomes of 66 patients with advanced hematological malignancies receiving two reduced-intensity conditioning regimens for allogeneic transplantation: fludarabine and low-dose TBI (flu/TBI, n=25), or fludarabine, antithymocyte globulin and BU (flu/ATG/BU, n=41). The selection criteria were based on the hypothesis that flu/TBI patients were expected to achieve autologous recovery in the event of non-engraftment. Sixty-three patients (95%) engrafted.

Effects of blood transfusions given after renal transplantation.

Background: Human leukocyte antigen (HLA) antibodies produced after transplantation are frequently measured in transplant recipients, because they are strongly associated with humoral rejection and graft loss. However, antibodies can be induced by posttransplant blood transfusions rather than by the graft, casting doubts about the possible role of antibodies in a patient with graft dysfunction.

Methods: We recorded the posttransplant transfusions in 746 patients transplanted during a 6-year period.

Value of posttransplant antibody tests in the evaluation of patients with renal graft dysfunction.

Posttransplant HLA antibodies correlate with C4d positive rejection and decreased graft survival. However, the diagnostic value of various antibody tests in the management of patients presenting with graft dysfunction is uncertain. Whether all or some patients should be tested, how often, what antibodies to test for and how to interpret results in presensitized or transfused patients, are issues still unresolved.

Measuring human complement activation by HLA antibodies.

Context: The clinical significance of HLA antibodies in transplantation depends on their ability to activate complement, which is measured by the standard complement-dependent cytotoxicity test. Recent reports indicate that C3b measurement on target cells may be a better indicator of human complement activation than standard cytotoxicity.

Objective: To determine the characteristics of the test, the role of other complement components, and the potential influence of the patient's own complement activity.

IVIG and HLA antibodies. Evidence for inhibition of complement activation but not for anti-idiotypic activity.

The immediate effects of IVIG can be due to the presence of anti-idiotypic antibodies or inhibition of complement, but there is limited data about these possible mechanisms specifically on HLA antibodies (HLA Abs). Potential blocking activity of IVIG on HLA Ab binding and complement activation was investigated by flow cytometry. IVIG did not inhibit the IgG binding of any of 23 sera from sensitized patients containing Abs to several different HLA specificities.

Human leukocyte antigen antibodies and human complement activation: role of IgG subclass, specificity, and cytotoxic potential.

Background: Human leukocyte antigen (HLA) antibodies are defined as complement (C) fixing and clinically relevant based upon the complement-dependent cytotoxicity (CDC) test. However, the sub-lytic activation of individual C components is of critical biologic significance. The requirements of HLA antibodies to activate human C are not known.

The changing causes of graft loss and death after kidney transplantation.

Background: The results of kidney transplantation have improved markedly over the last three decades. Despite this, patients still lose grafts and die. We sought to determine whether the causes of graft loss and death have changed over the last 30 years.

Susceptibility of liver allografts to high or low concentrations of preformed antibodies as measured by flow cytometry.

Liver grafts are more resistant to damage by HLA antibodies than other organ allografts, but it is not clear if the antibodies are associated with graft rejection or graft loss, or if different antibody concentrations have different effects. To explore potential associations between antibody concentrations and outcome, preformed IgG antibodies against donor cells were quantified by flow cytometry in 465 consecutive liver transplant recipients. Antibody-positive patients were classified according to whether they had high or low antibody concentrations and analyzed for possible correlation with graft rejection or graft loss.

Improved flow cytometric detection of donor-specific HLA class II antibodies by heat inactivation.

Flow cytometry is a powerful technique for T-cell crossmatching but is prone to false-positive reactions with B cells. In this study the flow cytometry crossmatch (FCXM) was performed in 319 cases, using the patient's serum untreated and incubated at 56 degrees C for 30 minutes. Heat treatment inhibited B-cell reactivity in 30 of 39 cases.

Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report.

Humoral or antibody-mediated rejection in cardiac transplant recipients is mediated by donor-specific cytotoxic antibodies and is histologically defined by linear deposits of immunoglobulin and complement in the myocardial capillaries. Antibody-mediated rejection often is accompanied by hemodynamic compromise and is associated with reduced long-term graft survival. Standard immunosuppression, designed to target T cell immune function, is largely ineffective against this B cell-driven process.

Obesity does not portend a bad outcome for kidney transplant recipients.

Background: Kidney transplant programs may avoid transplantation in obese patients because of reports indicating that obese patients have poorer outcomes than do nonobese patients. We recently reviewed our experience.

Methods: Patients receiving a kidney transplant between January 1, 1990 and December 31, 1999 were divided according to body mass index (BMI): group 1, BMI<25 (n=457); group 2, BMI> or =25 and <30 (n=278); and group 3, BMI> or =35 (n=98).